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Anti-Calbindin D-28K antibody

RRID:AB_2068336

Antibody ID

AB_2068336

Target Antigen

Calbindin D-28K human, mouse, rat

Proper Citation

(Millipore Cat# AB1778, RRID:AB_2068336)

Clonality

polyclonal antibody

Comments

seller recommendations: Immunohistochemistry; Western Blot; Immunohistochemistry (Paraffin)

Host Organism

rabbit

Vendor

Millipore

Highly segregated localization of the functionally related vps10p receptors sortilin and SorCS2 during neurodevelopment.

  • Boggild S
  • J. Comp. Neurol.
  • 2018 Jun 1

Literature context:


Abstract:

Nervous system development is a precisely orchestrated series of events requiring a multitude of intrinsic and extrinsic cues. Sortilin and SorCS2 are members of the Vps10p receptor family with complementary influence on some of these cues including the neurotrophins (NTs). However, the developmental time points where sortilin and SorCS2 exert their activities in conjunction or independently still remain unclear. In this study we present the characterization of the spatiotemporal expression pattern of sortilin and SorCS2 in the developing murine nervous system. Sortilin is highly expressed in the fetal nervous system with expression localized to distinct cell populations. Expression was high in neurons of the cortical plate and developing allocortex, as well as subpallial structures. Furthermore, the neuroepithelium lining the ventricles and the choroid plexus showed high expression of sortilin, together with the developing retina, spinal ganglia, and sympathetic ganglia. In contrast, SorCS2 was confined in a marked degree to the thalamus and, at E13.5, the floor plate from midbrain rostrally to spinal cord caudally. SorCS2 was also found in the ventricular zones of the ventral hippocampus and nucleus accumbens areas, in the meninges and in Schwann cells. Hence, sortilin and SorCS2 are extensively present in several distinct anatomical areas in the developing nervous system and are rarely co-expressed. Possible functions of sortilin and SorCS2 pertain to NT signaling, axon guidance and beyond. The present data will form the basis for hypotheses and study designs for unravelling the functions of sortilin and SorCS2 during the establishment of neuronal structures and connections.

Funding information:
  • NIGMS NIH HHS - R01 GM090158(United States)

Current concepts in the neuropathogenesis of mucolipidosis type IV.

  • Boudewyn LC
  • J. Neurochem.
  • 2018 May 16

Literature context:


Abstract:

Mucolipidosis type IV (MLIV) is an autosomal recessive, lysosomal storage disorder causing progressively severe intellectual disability, motor and speech deficits, retinal degeneration often culminating in blindness, and systemic disease causing a shortened lifespan. MLIV results from mutations in the gene MCOLN1 encoding the transient receptor potential channel mucolipin-1. It is an ultra-rare disease and is currently known to affect just over 100 diagnosed individuals. The last decade has provided a wealth of research focused on understanding the role of the enigmatic mucolipin-1 protein in cell and brain function and how its absence causes disease. This review explores our current understanding of the mucolipin-1 protein in relation to neuropathogenesis in MLIV and describes recent findings implicating mucolipin-1's important role in mTOR (mechanistic target of rapamycin) and TFEB (transcription factor EB) signaling feedback loops as well as in the function of the greater endosomal/lysosomal system. In addition to addressing the vital role of mucolipin-1 in the brain, we also report new data on the question of whether haploinsufficiency as would be anticipated in MCOLN1 heterozygotes is associated with any evidence of neuron dysfunction or disease. Greater insights into the role of mucolipin-1 in the nervous system can be expected to shed light not only on MLIV disease but also on numerous processes governing normal brain function. This article is protected by copyright. All rights reserved.

Funding information:
  • NIA NIH HHS - F32 AG027631(United States)
  • NICHD NIH HHS - P30 HD071593()
  • NICHD NIH HHS - R01 HD045561()
  • NICHD NIH HHS - U54 HD090260()
  • NINDS NIH HHS - R01 NS053677()

Opposing Effects of CREBBP Mutations Govern the Phenotype of Rubinstein-Taybi Syndrome and Adult SHH Medulloblastoma.

  • Merk DJ
  • Dev. Cell
  • 2018 Mar 26

Literature context:


Abstract:

Recurrent mutations in chromatin modifiers are specifically prevalent in adolescent or adult patients with Sonic hedgehog-associated medulloblastoma (SHH MB). Here, we report that mutations in the acetyltransferase CREBBP have opposing effects during the development of the cerebellum, the primary site of origin of SHH MB. Our data reveal that loss of Crebbp in cerebellar granule neuron progenitors (GNPs) during embryonic development of mice compromises GNP development, in part by downregulation of brain-derived neurotrophic factor (Bdnf). Interestingly, concomitant cerebellar hypoplasia was also observed in patients with Rubinstein-Taybi syndrome, a congenital disorder caused by germline mutations of CREBBP. By contrast, loss of Crebbp in GNPs during postnatal development synergizes with oncogenic activation of SHH signaling to drive MB growth, thereby explaining the enrichment of somatic CREBBP mutations in SHH MB of adult patients. Together, our data provide insights into time-sensitive consequences of CREBBP mutations and corresponding associations with human diseases.

Funding information:
  • NIGMS NIH HHS - GM068388(United States)

Loss of GPRC5B impairs synapse formation of Purkinje cells with cerebellar nuclear neurons and disrupts cerebellar synaptic plasticity and motor learning.

  • Sano T
  • Neurosci. Res.
  • 2018 Feb 23

Literature context:


Abstract:

GPRC5B is a membrane glycoprotein robustly expressed in mouse cerebellar Purkinje cells (PCs). Its function is unknown. In Gprc5b-/- mice that lack GPRC5B, PCs develop distal axonal swellings in deep cerebellar nuclei (DCN). Numerous misshapen mitochondria, which generated excessive amounts of reactive oxygen species (ROS), accumulated in these distal axonal swellings. In primary cell cultures of Gprc5b-/- PCs, pharmacological reduction of ROS prevented the appearance of such swellings. To examine the physiological role of GPRC5B in PCs, we analyzed cerebellar synaptic transmission and cerebellum-dependent motor learning in Gprc5b-/- mice. Patch-clamp recordings in cerebellum slices in vitro revealed that the induction of long-term depression (LTD) at parallel fiber-PC synapses was normal in adult Gprc5b-/- mice, whereas the induction of long-term potentiation (LTP) at mossy fiber-DCN neuron synapses was attenuated in juvenile Gprc5b-/- mice. In Gprc5b-/- mice, long-term motor learning was impaired in both the rotarod test and the horizontal optokinetic response eye movement (HOKR) test. These observations suggest that GPRC5B plays not only an important role in the development of distal axons of PCs and formation of synapses with DCN neurons, but also in the synaptic plasticity that underlies long-term motor learning.

Funding information:
  • NCI NIH HHS - R01 CA160371(United States)

Meis1 Coordinates Cerebellar Granule Cell Development by Regulating Pax6 Transcription, BMP Signaling and Atoh1 Degradation.

  • Owa T
  • J. Neurosci.
  • 2018 Jan 31

Literature context:


Abstract:

Cerebellar granule cell precursors (GCPs) and granule cells (GCs) represent good models to study neuronal development. Here, we report that the transcription factor myeloid ectopic viral integration site 1 homolog (Meis1) plays pivotal roles in the regulation of mouse GC development. We found that Meis1 is expressed in GC lineage cells and astrocytes in the cerebellum during development. Targeted disruption of the Meis1 gene specifically in the GC lineage resulted in smaller cerebella with disorganized lobules. Knock-down/knock-out (KO) experiments for Meis1 and in vitro assays showed that Meis1 binds to an upstream sequence of Pax6 to enhance its transcription in GCPs/GCs and also suggested that the Meis1-Pax6 cascade regulates morphology of GCPs/GCs during development. In the conditional KO (cKO) cerebella, many Atoh1-positive GCPs were observed ectopically in the inner external granule layer (EGL) and a similar phenomenon was observed in cultured cerebellar slices treated with a bone morphogenic protein (BMP) inhibitor. Furthermore, expression of Smad proteins and Smad phosphorylation were severely reduced in the cKO cerebella and Meis1-knock-down GCPs cerebella. Reduction of phosphorylated Smad was also observed in cerebellar slices electroporated with a Pax6 knock-down vector. Because it is known that BMP signaling induces Atoh1 degradation in GCPs, these findings suggest that the Meis1-Pax6 pathway increases the expression of Smad proteins to upregulate BMP signaling, leading to degradation of Atoh1 in the inner EGL, which contributes to differentiation from GCPs to GCs. Therefore, this work reveals crucial functions of Meis1 in GC development and gives insights into the general understanding of the molecular machinery underlying neural differentiation from neural progenitors.SIGNIFICANCE STATEMENT We report that myeloid ectopic viral integration site 1 homolog (Meis1) plays pivotal roles in the regulation of mouse granule cell (GC) development. Here, we show Meis1 is expressed in GC precursors (GCPs) and GCs during development. Our knock-down and conditional knock-out (cKO) experiments and in vitro assays revealed that Meis1 is required for proper cerebellar structure formation and for Pax6 transcription in GCPs and GCs. The Meis1-Pax6 cascade regulates the morphology of GCs. In the cKO cerebella, Smad proteins and bone morphogenic protein (BMP) signaling are severely reduced and Atoh1-expressing GCPs are ectopically detected in the inner external granule layer. These findings suggest that Meis1 regulates degradation of Atoh1 via BMP signaling, contributing to GC differentiation in the inner EGL, and should provide understanding into GC development.

Funding information:
  • British Heart Foundation - RG/07/008/23674(United Kingdom)

Arid1b haploinsufficiency disrupts cortical interneuron development and mouse behavior.

  • Jung EM
  • Nat. Neurosci.
  • 2017 Dec 12

Literature context:


Abstract:

Haploinsufficiency of the AT-rich interactive domain 1B (ARID1B) gene causes autism spectrum disorder and intellectual disability; however, the neurobiological basis for this is unknown. Here we generated Arid1b-knockout mice and examined heterozygotes to model human patients. Arid1b-heterozygous mice showed a decreased number of cortical GABAergic interneurons and reduced proliferation of interneuron progenitors in the ganglionic eminence. Arid1b haploinsufficiency also led to an imbalance between excitatory and inhibitory synapses in the cerebral cortex. Furthermore, we found that Arid1b haploinsufficiency suppressed histone H3 lysine 9 acetylation (H3K9ac) overall and particularly reduced H3K9ac of the Pvalb promoter, resulting in decreased transcription. Arid1b-heterozygous mice exhibited abnormal cognitive and social behaviors, which were rescued by treatment with a positive allosteric GABAA receptor modulator. Our results demonstrate a critical role for Arid1b in interneuron development and behavior and provide insight into the pathogenesis of autism spectrum disorder and intellectual disability.

Funding information:
  • NHLBI NIH HHS - K08 HL089150(United States)
  • NIGMS NIH HHS - P20 GM103471()
  • NINDS NIH HHS - R01 NS091220()

Calmodulin-like skin protein protects against spatial learning impairment in a mouse model of Alzheimer disease.

  • Kusakari S
  • J. Neurochem.
  • 2017 Nov 23

Literature context:


Abstract:

Humanin and calmodulin-like skin protein (CLSP) inhibits Alzheimer disease (AD)-related neuronal cell death via the heterotrimeric humanin receptor in vitro. It has been suggested that CLSP is a central agonist of the heterotrimeric humanin receptor in vivo. To investigate the role of CLSP in the AD pathogenesis in vivo, we generated mouse CLSP-1 transgenic mice, crossed them with the APPswe/PSEN1dE9 mice, a model mouse of AD, and examined the effect of CLSP over-expression on the pathological phenotype of the AD mouse model. We found that over-expression of the mouse CLSP-1 gene attenuated spatial learning impairment, the loss of a presynaptic marker synaptophysin, and the inactivation of STAT3 in the APPswe/PSEN1dE9 mice. On the other hand, CLSP over-expression did not affect levels of Aβ, soluble Aβ oligomers, or gliosis. These results suggest that the CLSP-mediated attenuation of memory impairment and synaptic loss occurs in an Aβ-independent manner. The results of this study may serve as a hint to the better understanding of the AD pathogenesis and the development of AD therapy.

Virus-Mediated Genome Editing via Homology-Directed Repair in Mitotic and Postmitotic Cells in Mammalian Brain.

  • Nishiyama J
  • Neuron
  • 2017 Nov 15

Literature context:


Abstract:

Precise genome editing via homology-directed repair (HDR) in targeted cells, particularly in vivo, provides an invaluable tool for biomedical research. However, HDR has been considered to be largely restricted to dividing cells, making it challenging to apply the technique in postmitotic neurons. Here we show that precise genome editing via HDR is possible in mature postmitotic neurons as well as mitotic cells in mice brain by combining CRISPR-Cas9-mediated DNA cleavage and the efficient delivery of donor template with adeno-associated virus (AAV). Using this strategy, we achieved efficient tagging of endogenous proteins in primary and organotypic cultures in vitro and developing, adult, aged, and pathological brains in vivo. Thus, AAV- and CRISPR-Cas9-mediated HDR will be broadly useful for precise genome editing in basic and translational neuroscience.

Funding information:
  • NIMH NIH HHS - R01 MH080047()
  • NINDS NIH HHS - DP1 NS096787()

ARX polyalanine expansion mutations lead to migration impediment in the rostral cortex coupled with a developmental deficit of calbindin-positive cortical GABAergic interneurons.

  • Lee K
  • Neuroscience
  • 2017 Aug 15

Literature context:


Abstract:

The Aristaless-related homeobox gene (ARX) is indispensable for interneuron development. Patients with ARX polyalanine expansion mutations of the first two tracts (namely PA1 and PA2) suffer from intellectual disability of varying severity, with seizures a frequent comorbidity. The impact of PA1 and PA2 mutations on the brain development is unknown, hindering the search for therapeutic interventions. Here, we characterized the disturbances to cortical interneuron development in mice modeling the two most common ARX polyalanine expansion mutations in human. We found a consistent ∼40-50% reduction of calbindin-positive interneurons, but not Stt+ or Cr+ interneurons, within the cortex of newborn hemizygous mice (p=0.024) for both mutant strains compared to wildtype (p=0.011). We demonstrate that this was a consequence of calbindin precursor cells being arrested or delayed at the ventral subpallium en route of tangential migration. Ex-vivo assay validated this migration deficit in PA1 cells (p=0.0002) suggesting that the defect is contributed by intrinsic loss of Arx function within migrating cells. Both humans and mice with PA1 mutations present with severe clinical features, including intellectual disability and infantile spasms. Our data further demonstrated the pathogenic mechanism was robustly shared between PA1 and PA2 mutations, as previously reported including Arx protein reduction and overlapping transcriptome profiles within the developing mouse brains. Data from our study demonstrated that cortical calbindin interneuron development and migration is negatively affected by ARX polyalanine expansion mutations. Understanding the cellular pathogenesis contributing to disease manifestation is necessary to screen efficacy of potential therapeutic interventions.

Valnoctamide Inhibits Cytomegalovirus Infection in Developing Brain and Attenuates Neurobehavioral Dysfunctions and Brain Abnormalities.

  • Ornaghi S
  • J. Neurosci.
  • 2017 Jul 19

Literature context:


Abstract:

Cytomegalovirus (CMV) is the most common infectious cause of brain defects and neurological dysfunction in developing human babies. Due to the teratogenicity and toxicity of available CMV antiviral agents, treatment options during early development are markedly limited. Valnoctamide (VCD), a neuroactive mood stabilizer with no known teratogenic activity, was recently demonstrated to have anti-CMV potential. However, it is not known whether this can be translated into an efficacious therapeutic effect to improve CMV-induced adverse neurological outcomes. Using multiple models of CMV infection in the developing mouse brain, we show that subcutaneous low-dose VCD suppresses CMV by reducing the level of virus available for entry into the brain and by acting directly within the brain to block virus replication and dispersal. VCD during the first 3 weeks of life restored timely acquisition of neurological milestones in neonatal male and female mice and rescued long-term motor and behavioral outcomes in juvenile male mice. CMV-mediated brain defects, including decreased brain size, cerebellar hypoplasia, and neuronal loss, were substantially attenuated by VCD. No adverse side effects on neurodevelopment of uninfected control mice receiving VCD were detected. Treatment of CMV-infected human fetal astrocytes with VCD reduced both viral infectivity and replication by blocking viral particle attachment to the cell, a mechanism that differs from available anti-CMV drugs. These data suggest that VCD during critical periods of neurodevelopment can effectively suppress CMV replication in the brain and safely improve both immediate and long-term neurological outcomes.SIGNIFICANCE STATEMENT Cytomegalovirus (CMV) can irreversibly damage the developing brain. No anti-CMV drugs are available for use during fetal development, and treatment during the neonatal period has substantial limitations. We studied the anti-CMV actions of valnoctamide (VCD), a psychiatric sedative that appears to lack teratogenicity and toxicity, in the newborn mouse brain, a developmental period that parallels that of an early second-trimester human fetus. In infected mice, subcutaneous VCD reaches the brain and suppresses viral replication within the CNS, rescuing the animals from CMV-induced brain defects and neurological problems. Treatment of uninfected control animals exerts no detectable adverse effects. VCD also blocks CMV replication in human fetal brain cells.

Supporting cells remove and replace sensory receptor hair cells in a balance organ of adult mice.

  • Bucks SA
  • Elife
  • 2017 Mar 6

Literature context:


Abstract:

Vestibular hair cells in the inner ear encode head movements and mediate the sense of balance. These cells undergo cell death and replacement (turnover) throughout life in non-mammalian vertebrates. However, there is no definitive evidence that this process occurs in mammals. We used fate-mapping and other methods to demonstrate that utricular type II vestibular hair cells undergo turnover in adult mice under normal conditions. We found that supporting cells phagocytose both type I and II hair cells. Plp1-CreERT2-expressing supporting cells replace type II hair cells. Type I hair cells are not restored by Plp1-CreERT2-expressing supporting cells or by Atoh1-CreERTM-expressing type II hair cells. Destruction of hair cells causes supporting cells to generate 6 times as many type II hair cells compared to normal conditions. These findings expand our understanding of sensorineural plasticity in adult vestibular organs and further elucidate the roles that supporting cells serve during homeostasis and after injury.

Calretinin and Neuropeptide Y interneurons are differentially altered in the motor cortex of the SOD1G93A mouse model of ALS.

  • Clark RM
  • Sci Rep
  • 2017 Mar 15

Literature context:


Abstract:

Increasing evidence indicates an excitatory/inhibitory imbalance may have a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS). Impaired inhibitory circuitry is consistently reported in the motor cortex of both familial and sporadic patients, closely associated with cortical hyperexcitability and ALS onset. Inhibitory network dysfunction is presumably mediated by intra-cortical inhibitory interneurons, however, the exact cell types responsible are yet to be identified. In this study we demonstrate dynamic changes in the number of calretinin- (CR) and neuropeptide Y-expressing (NPY) interneurons in the motor cortex of the familial hSOD1G93A ALS mouse model, suggesting their potential involvement in motor neuron circuitry defects. We show that the density of NPY-populations is significantly decreased by ~17% at symptom onset (8 weeks), and by end-stage disease (20 weeks) is significantly increased by ~30%. Conversely, the density of CR-populations is progressively reduced during later symptomatic stages (~31%) to end-stage (~36%), while CR-expressing interneurons also show alteration of neurite branching patterns at symptom onset. We conclude that a differential capacity for interneurons exists in the ALS motor cortex, which may not be a static phenomenon, but involves early dynamic changes throughout disease, implicating specific inhibitory circuitry.

Sex-Dependent Regulation of Aromatase-Mediated Synaptic Plasticity in the Basolateral Amygdala.

  • Bender RA
  • J. Neurosci.
  • 2017 Feb 8

Literature context:


Abstract:

The basolateral amygdala (BLA) integrates sensory input from cortical and subcortical regions, a function that requires marked synaptic plasticity. Here we provide evidence that cytochrome P450 aromatase (AROM), the enzyme converting testosterone to 17β-estradiol (E2), contributes to the regulation of this plasticity in a sex-specific manner. We show that AROM is expressed in the BLA, particularly in the basolateral nucleus (BL), in male and female rodents. Systemic administration of the AROM inhibitor letrozole reduced spine synapse density in the BL of adult female mice but not in the BL of male mice. Similarly, in organotypic corticoamygdalar slice cultures from immature rats, treatment with letrozole significantly reduced spine synapses in the BL only in cultures derived from females. In addition, letrozole sex-specifically altered synaptic properties in the BL: in acute slices from juvenile (prepubertal) female rats, wash-in of letrozole virtually abolished long-term potentiation (LTP), whereas it did not prevent the generation of LTP in the slices from males. Together, these data indicate that neuron-derived E2 modulates synaptic plasticity in rodent BLA sex-dependently. As protein expression levels of AROM, estrogen and androgen receptors did not differ between males and females and were not sex-specifically altered by letrozole, the findings suggest sex-specific mechanisms of E2 signaling.SIGNIFICANCE STATEMENT The basolateral amygdala (BLA) is a key structure of the fear circuit. This research reveals a sexually dimorphic regulation of synaptic plasticity in the BLA involving neuronal aromatase, which produces the neurosteroid 17β-estradiol (E2). As male and female neurons in rodent BLA responded differently to aromatase inhibition both in vivo and in vitro, our findings suggest that E2 signaling in BLA neurons is regulated sex-dependently, presumably via mechanisms that have been established during sexual determination. These findings could be relevant for the understanding of sex differences in mood disorders and of the side effects of cytochrome P450 aromatase inhibitors, which are frequently used for breast cancer therapy.

A Sexually Dimorphic Area of the Dorsal Hypothalamus in Mice and Common Marmosets.

  • Moe Y
  • Endocrinology
  • 2016 Dec 11

Literature context:


Abstract:

We found a novel sexually dimorphic area (SDA) in the dorsal hypothalamus (DH) of mice. The SDA-DH was sandwiched between 2 known male-biased sexually dimorphic nuclei, the principal nucleus of the bed nucleus of the stria terminalis and the calbindin-sexually dimorphic nucleus, and exhibited a female-biased sex difference in neuronal cell density. The density of neurons in the SDA-DH was increased in male mice by orchidectomy on the day of birth and decreased in female mice by treatment with testosterone, dihydrotestosterone, or estradiol within 5 days after birth. These findings indicate that the SDA-DH is defeminized under the influence of testicular testosterone, which acts via both directly by binding to the androgen receptor, and indirectly by binding to the estrogen receptor after aromatization. We measured the activity of SDA-DH neurons with c-Fos, a neuronal activity marker, in female mice during maternal and sexual behaviors. The number of c-Fos-expressing neurons in the SDA-DH of female mice was negatively correlated with maternal behavior performance. However, the number of c-Fos-expressing neurons did not change during female sexual behavior. These findings suggest that the SDA-DH contains a neuronal cell population, the activity of which decreases in females exhibiting higher performance of maternal behavior, but it may contribute less to female sexual behavior. Additionally, we examined the brain of common marmosets and found an area that appears to be homologous with the mouse SDA-DH. The sexually dimorphic structure identified in this study is not specific to mice and may be found in other species.

In Utero Exposure to Valproic Acid Induces Neocortical Dysgenesis via Dysregulation of Neural Progenitor Cell Proliferation/Differentiation.

  • Fujimura K
  • J. Neurosci.
  • 2016 Oct 19

Literature context:


Abstract:

Valproic acid (VPA), a widely used antiepileptic drug, is an inhibitor of histone deacetylases, which epigenetically modify cell proliferation/differentiation in developing tissues. A series of recent clinical studies in humans reported that VPA exposure in utero impaired histogenesis and the development of the central nervous system, leading to increased risks of congenital malformation and the impairment of higher brain functions in children. In the present study conducted in mice, we report that VPA exposure in utero (1) increases the amount of acetylated histone proteins, (2) alters the expression of G1-phase regulatory proteins, (3) inhibits the cell cycle exit of neural progenitor cells during the early stage of neocortical histogenesis, and (4) increases the production of projection neurons distributed in the superficial neocortical layers in embryonic brains. Together, our findings show that VPA exposure in utero alters proliferation/differentiation characteristics of neural progenitor cells and hence leads to the neocortical dysgenesis. SIGNIFICANCE STATEMENT: This study provides new insight into the mechanisms of how an altered in utero environment, such as drug exposure, affects the generation of neurons prenatally. The antiepileptic drug valproic acid (VPA) is a good target molecule as in utero exposure to VPA has been repeatedly reported to increase the risk of nervous system malformations and to impair higher brain functions in children. We show that VPA decreases the probability of differentiation of the neural progenitor cells (NPCs) in mice, resulting in an abnormally increased number of projection neurons in the superficial layers of the neocortex. Further, we suggest that histone deacetylase inhibition by VPA may be involved in the dysregulation of proliferation/differentiation characteristics of NPCs.

Erratum to: Rectocutaneous fistula with transmigration of the suture: a rare delayed complication of vault fixation with the sacrospinous ligament.

  • Kadam PD
  • Int Urogynecol J
  • 2016 Mar 25

Literature context:


Abstract:

There was an oversight in the Authorship of a recent Images in Urogynecology article titled: Rectocutaneous fistula with transmigration of the suture: a rare delayed complication of vault fixation with the sacrospinous ligament (DOI 10.1007/ s00192-015-2823-5). We would like to include Adj A/P Han How Chuan’s name in the list of authors. Adj A/P Han is a Senior Consultant and Department Head of Urogynaecology at the KK Hospital for Women and Children, Singapore.

Funding information:
  • NHGRI NIH HHS - R01HG005855(United States)

The Expression of Tubb2b Undergoes a Developmental Transition in Murine Cortical Neurons.

  • Breuss M
  • J. Comp. Neurol.
  • 2015 Oct 15

Literature context:


Abstract:

The development of the mammalian brain requires the generation, migration, and differentiation of neurons, cellular processes that are dependent on a dynamic microtubule cytoskeleton. Mutations in tubulin genes, which encode for the structural subunits of microtubules, cause detrimental neurological disorders known as the tubulinopathies. The disease spectra associated with different tubulin genes are overlapping but distinct, an observation believed to reflect functional specification of this multigene family. Perturbation of the β-tubulin TUBB2B is known to cause polymicrogyria, pachygyria, microcephaly, and axon guidance defects. Here we provide a detailed analysis of the expression pattern of its murine homolog Tubb2b. The generation and characterization of BAC-transgenic eGFP reporter mouse lines has revealed that it is highly expressed in progenitors and postmitotic neurons during cortical development. This contrasts with the 8-week-old cortex, in which Tubb2b expression is restricted to macroglia, and expression is almost completely absent in mature neurons. This developmental transition in neurons is mirrored in the adult hippocampus and the cerebellum but is not a universal feature of Tubb2b; its expression persists in a population of postmitotic neurons in the 8-week-old retina. We propose that the dynamic spatial and temporal expression of Tubb2b reflects specific functional requirements of the microtubule cytoskeleton.

Cytogenesis in the adult monkey motor cortex: perivascular NG2 cells are the major adult born cell type.

  • Stanton GB
  • J. Comp. Neurol.
  • 2015 Apr 15

Literature context:


Abstract:

We used confocal microscopy and immunohistochemistry (IHC) to look for new cells in the motor cortex of adult macaque monkeys that might form the cellular bases of improved brain function from exercise. Twenty-four female Macaca fascicularis monkeys divided into groups by age (10-12 years, 15-17 years), postexercise survival periods, and controls, received 10 weekly injections of the thymidine analog, bromodeoxyuridine (BrdU) to mark new cells. Sixteen monkeys survived 15 weeks (5 weeks postexercise) and 8 monkeys survived 27 weeks (12 weeks postexercise) after initial BrdU injections. Additionally, five Macaca mulatta female monkeys (∼5.5-7 years) received single injections of BrdU and survived 2 days, 2 weeks, and 6 weeks after BrdU injections. Neural and glial antibodies were used to identify new cell phenotypes and to look for changes in proportions of these cells with respect to time and experimental conditions. No BrdU(+) /DCx(+) cells were found but about 7.5% of new cells were calretinin-positive (Cr(+) ). BrdU(+) /GABA(+) (gamma-aminobutyric acid) cells were also found but no new Cr(+) or GABA(+) cells colabeled with a mature neuron marker, NeuN or chondroitin sulfate antibody, NG2. The proportion of new cells that were NG2(+) was about 85% for short and long survival monkeys of which two, newly described perivascular phenotypes (Pldv and Elu) and a small percentage of pericytes (2.5%) comprised 44% and 51% of the new NG2(+) cells, respectively. Proportions of NG2(+) phenotypes were affected by post-BrdU survival periods, monkey age, and possibly a postexercise sedentary period but no direct effect of exercise was found.

Immunofluorescent visualization of mouse interneuron subtypes.

  • Molgaard S
  • F1000Res
  • 2014 Dec 16

Literature context:


Abstract:

The activity of excitatory neurons is controlled by a highly diverse population of inhibitory interneurons. These cells show a high level of physiological, morphological and neurochemical heterogeneity, and play highly specific roles in neuronal circuits. In the mammalian hippocampus, these are divided into 21 different subtypes of GABAergic interneurons based on their expression of different markers, morphology and their electrophysiological properties. Ideally, all can be marked using an antibody directed against the inhibitory neurotransmitter GABA, but parvalbumin, calbindin, somatostatin, and calretinin are also commonly used as markers to narrow down the specific interneuron subtype. Here, we describe a journey to find the necessary immunological reagents for studying GABAergic interneurons of the mouse hippocampus. Based on web searches there are several hundreds of different antibodies on the market directed against these four markers. Searches in the literature databases allowed us to narrow it down to a subset of antibodies most commonly used in publications. However, in our hands the most cited ones did not work for immunofluorescence stainings of formaldehyde fixed tissue sections and cultured hippocampal neurons, and we had to immunostain our way through thirteen different commercial antibodies before finally finding a suitable antibody for each of the four markers. The antibodies were evaluated based on signal-to-noise ratios as well as if positive cells were found in layers of the hippocampus where they have previously been described. Additionally, the antibodies were also tested on sections from mouse spinal cord with similar criteria for specificity of the antibodies. Using the antibodies with a high rating on pAbmAbs, an antibody review database, stainings with high signal-to-noise ratios and location of the immunostained cells in accordance with the literature could be obtained, making these antibodies suitable choices for studying the GABAergic system.

Large basolateral processes on type II hair cells are novel processing units in mammalian vestibular organs.

  • Pujol R
  • J. Comp. Neurol.
  • 2014 Oct 1

Literature context:


Abstract:

Sensory receptors in the vestibular system (hair cells) encode head movements and drive central motor reflexes that control gaze, body movements, and body orientation. In mammals, type I and II vestibular hair cells are defined by their shape, contacts with vestibular afferent nerves, and membrane conductance. Here we describe unique morphological features of type II vestibular hair cells in mature rodents (mice and gerbils) and bats. These features are cytoplasmic processes that extend laterally from the hair cell base and project under type I hair cells. Closer analysis of adult mouse utricles demonstrated that the basolateral processes of type II hair cells vary in shape, size, and branching, with the longest processes extending three to four hair cell widths. The hair cell basolateral processes synapse upon vestibular afferent nerves and receive inputs from vestibular efferent nerves. Furthermore, some basolateral processes make physical contacts with the processes of other type II hair cells, forming some sort of network among type II hair cells. Basolateral processes are rare in perinatal mice and do not attain their mature form until 3-6 weeks of age. These observations demonstrate that basolateral processes are significant signaling regions of type II vestibular hair cells and suggest that type II hair cells may directly communicate with each other, which has not been described in vertebrates.

Early remodeling of Müller cells in the rd/rd mouse model of retinal dystrophy.

  • Chua J
  • J. Comp. Neurol.
  • 2013 Aug 1

Literature context:


Abstract:

We studied the anatomical remodeling and gliosis of retinal Müller cells in the rd/rd mouse model of photoreceptor degeneration. A computational calculation of glutamine synthetase immunoreactivity was developed so we could specifically quantify changes in Müller cell anatomy between control mice (C57Bl/6) and the dystrophic strain. We found no change in the number of Müller cell somata between mice strains, indicating no cell proliferation as a function of development and degeneration. The retinal area occupied by the total Müller cell body (soma and processes) was significantly less in the rd/rd mouse retina compared with control mice. When only the outer retina was considered, we found rd/rd Müller cell processes were dramatically reduced during the cone phase of photoreceptor degeneration. However, at older ages an increase in Müller cell processes was seen. Conversely, glial fibrillary acidic protein (GFAP) expression showed a significant increase during cone degeneration followed by a reduction in older ages. Müller cell electrophysiology, particularly K(+) currents and membrane potential, was similar between rd/rd and control Müller cells during cone degeneration. Together, these results show that glial remodeling in the rd/rd retina follows separate phases-an initial conservative glial response involving the loss of Müller cells processes, hyperexpression of GFAP, and preservation of normal electrophysiology followed by an active growth of Müller cell processes, glial seal formation, and attenuation of GFAP expression after complete photoreceptor loss.

Funding information:
  • NIGMS NIH HHS - RC2 GM092519(United States)

Inherited neuroaxonal dystrophy in dogs causing lethal, fetal-onset motor system dysfunction and cerebellar hypoplasia.

  • Fyfe JC
  • J. Comp. Neurol.
  • 2010 Sep 15

Literature context:


Abstract:

Neuroaxonal dystrophy in brainstem, spinal cord tracts, and spinal nerves accompanied by cerebellar hypoplasia was observed in a colony of laboratory dogs. Fetal akinesia was documented by ultrasonographic examination. At birth, affected puppies exhibited stereotypical positioning of limbs, scoliosis, arthrogryposis, pulmonary hypoplasia, and respiratory failure. Regional hypoplasia in the central nervous system was apparent grossly, most strikingly as underdeveloped cerebellum and spinal cord. Histopathologic abnormalities included swollen axons and spheroids in brainstem and spinal cord tracts; reduced cerebellar foliation, patchy loss of Purkinje cells, multifocal thinning of the external granular cell layer, and loss of neurons in the deep cerebellar nuclei; spheroids and loss of myelinated axons in spinal roots and peripheral nerves; increased myocyte apoptosis in skeletal muscle; and fibrofatty connective tissue proliferation around joints. Breeding studies demonstrated that the canine disorder is a fully penetrant, simple autosomal recessive trait. The disorder demonstrated a type and distribution of lesions homologous to that of human infantile neuroaxonal dystrophy (INAD), most commonly caused by mutations of phospholipase A2 group VI gene (PLA2G6), but alleles of informative markers flanking the canine PLA2G6 locus did not associate with the canine disorder. Thus, fetal-onset neuroaxonal dystrophy in dogs, a species with well-developed genome mapping resources, provides a unique opportunity for additional disease gene discovery and understanding of this pathology.

Funding information:
  • NIGMS NIH HHS - 5R01GM72649(United States)

Estrogen configures sexual dimorphism in the preoptic area of C57BL/6J and ddN strains of mice.

  • Orikasa C
  • J. Comp. Neurol.
  • 2010 Sep 1

Literature context:


Abstract:

Immunohistochemistry using a calbindin D28k antibody revealed a marked sex difference in neuronal distribution in the central portion of the medial preoptic area in C57BL/6J and ddN strains of mice when the animals were sacrificed on D65 (D1 = the day of birth). Male mice had a distinct ellipsoidal cell aggregate, whereas females lacked such a structure. This sex difference was not observed in Nissl-stained sections. Co-localization of calbindin D28k and the neuron-specific nuclear protein NeuN confrmed that the cells in the aggregate were neurons. The aggregates were larger in males than in females in both strains. When observed on D65, males orchidectomized on D1 had smaller aggregates. However, daily injections of 2 microg estradiol benzoate through D1-D5 as well as a single injection of 100 microg testosterone propionate on D1 enlarged the aggregates in females, but a single injection of 100 microg dihydrotestosterone on D1 had no effect on the female phenotype. Similar endocrine manipulations had no effects in adult animals of both sexes. Thus, the calbindin-immunoreactive cell aggregates in the preoptic area of C57BL/6J and ddN mice are homologous to the sexually dimorphic nucleus of the rat preoptic area in terms of the morphology and sex steroid-dependent organization.

Funding information:
  • NCRR NIH HHS - 5 P41 RR05969-04(United States)

Diverse interneuron populations have highly specific interconnectivity in the rat piriform cortex.

  • Gavrilovici C
  • J. Comp. Neurol.
  • 2010 May 1

Literature context:


Abstract:

Previous studies have suggested that the patterns of innervation and high interconnectivity of the piriform cortex (PC) provide for strong olfactory hippocampal memory; however, these same attributes may create high seizurogenic tendencies. Thus, understanding this wiring is important from a physiological and pathophysiological perspective. Distinct interneurons expressing differing calcium binding proteins (CBPs), parvalbumin (PV), calbindin (CB), and calretinin (CR), have been shown to exist in PC. However, a comprehensive examination of the distribution and innervation patterns of these neurons has not been done. Thus the purpose of this study was to combine the analysis of the CBP cell localization with analysis of their innervation patterns. Each type was differentially localized in the three layers of the PC. Only CR-positive neurons were found in layer 1. PV and CB are coexpressed in layers 2-3, most expressing both PV and CB. A morphological estimate of the dendritic extent for each subtype showed that PV and PV/CB cells demonstrated equally wide, horizontal and vertical arborizations, whereas CB cells had wide horizontal and restricted vertical arborizations. CR cells had restricted horizontal and very long vertical arborizations. Postsynaptic morphological targeting was also found to be specific, namely, PV(+) and PV/CB(+) nerve terminals (NTs) innervate perisomatic regions of principal cells. CR(+) NTs innervate only dendrites of principal cells, and CB(+) NTs innervate both somata and dendrites of principal cells. These data show highly complex innervation patterns for all of the CBP interneurons of the PC and form a basis for further studies in the plasticity of this region.

Inhibitory neurons in the anterior piriform cortex of the mouse: classification using molecular markers.

  • Suzuki N
  • J. Comp. Neurol.
  • 2010 May 15

Literature context:


Abstract:

The primary olfactory cortex (or piriform cortex, PC) is attracting increasing attention as a model system for the study of cortical sensory processing, yet little is known about inhibitory neurons in the PC. Here we provide the first systematic classification of GABA-releasing interneurons in the anterior PC of mice, based on the expression of molecular markers. Our experiments used GAD67-GFP transgenic mice, in which gamma-aminobutyric acid (GABA)-containing cells are labeled with green fluorescent protein (GFP). We first confirmed, using paired whole-cell recordings, that GFP(+) neurons in the anterior PC of GAD67-GFP mice are functionally GABAergic. Next, we performed immunolabeling of GFP(+) cells to quantify their expression of every possible pairwise combination of seven molecular markers: calbindin, calretinin, parvalbumin, cholecystokinin, neuropeptide Y, somatostatin, and vasoactive intestinal peptide. We found that six main categories of interneurons could be clearly distinguished in the anterior PC, based on the size and laminar location of their somata, intensity of GFP fluorescence, patterns of axonal projections, and expression of one or more of the seven markers. A number of rarer categories of interneurons could also be identified. These data provide a road map for further work that examines the functional properties of the six main classes of interneurons. Together, this information elucidates the cellular architecture of the PC and provides clues about the roles of GABAergic interneurons in olfactory processing.

Expression of PTPRO in the interneurons of adult mouse olfactory bulb.

  • Kotani T
  • J. Comp. Neurol.
  • 2010 Jan 10

Literature context:


Abstract:

PTPRO is a receptor-type protein tyrosine phosphatase (PTP) with a single catalytic domain in its cytoplasmic region and multiple fibronectin type III-like domains in its extracellular region. In the chick, PTPRO mRNA has been shown to be particularly abundant in embryonic brain, and PTPRO is implicated in axon growth and guidance during embryonic development. However, the temporal and spatial expression of PTPRO protein in the mammalian CNS, particularly in the juvenile and adult mammalian brain, has not been evaluated in any detail. By immunohistofluorescence analysis with a monoclonal antibody to PTPRO, we show that PTPRO is widely expressed throughout the mouse brain from embryonic day 16 to postnatal day 1, while expression is largely confined to the olfactory bulb (OB) and olfactory tubercle in the adult brain. In the OB, PTPRO protein is expressed predominantly in the external plexiform layer, the granule cell layer, and the glomerular layer (GL). In these regions, expression of PTPRO is predominant in interneurons such as gamma-aminobutyric acid (GABA)-ergic or calretinin (CR)-positive granule cells. In addition, PTPRO is expressed in GABAergic, CR-positive, tyrosine hydroxylase-positive, or neurocalcin-positive periglomerular cells in the GL. Costaining of PTPRO with other neuronal markers suggests that PTPRO is likely to be localized to the dendrites or dendritic spines of these olfactory interneurons. Thus, PTPRO might participate in regulation of dendritic morphology or synapse formation of interneurons in the adult mouse OB.