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Cleaved-CASP3 (Asp175) Antibody

RRID:AB_10665003

Antibody ID

AB_10665003

Target Antigen

Cleaved-CASP3 (Asp175) human

Proper Citation

(Abgent Cat# AP3725a, RRID:AB_10665003)

Clonality

monoclonal antibody

Comments

manufacturer recommendations: ELISA; Western Blot; IHC,DB,E

Vendor

Abgent

Cat Num

AP3725a

Publications that use this research resource

Differential Neurotoxicity Related to Tetracycline Transactivator and TDP-43 Expression in Conditional TDP-43 Mouse Model of Frontotemporal Lobar Degeneration.

  • Kukreja L
  • J. Neurosci.
  • 2018 Jul 4

Literature context:


Abstract:

Frontotemporal lobar degeneration (FTLD) is among the most prevalent dementias of early-onset. Pathologically, FTLD presents with tauopathy or TAR DNA-binding protein 43 (TDP-43) proteinopathy. A biallelic mouse model of FTLD was produced on a mix FVB/129SVE background overexpressing wild-type human TDP-43 (hTDP-43) using tetracycline transactivator (tTA), a system widely used in mouse models of neurological disorders. tTA activates hTDP-43, which is placed downstream of the tetracycline response element. The original study on this transgenic mouse found hippocampal degeneration following hTDP-43 expression, but did not account for independent effects of tTA protein. Here, we initially analyzed the neurotoxic effects of tTA in postweaning age mice of either sex using immunostaining and area measurements of select brain regions. We observed tTA-dependent toxicity selectively in the hippocampus affecting the dentate gyrus significantly more than CA fields, whereas hTDP-43-dependent toxicity in bigenic mice occurred in most other cortical regions. Atrophy was associated with inflammation, activation of caspase-3, and loss of neurons. The atrophy associated with tTA expression was rescuable by the tetracycline analog, doxycycline, in the diet. MRI studies corroborated the patterns of atrophy. tTA-induced degeneration was strain-dependent and was rescued by moving the transgene onto a congenic C57BL/6 background. Despite significant hippocampal atrophy, behavioral tests in bigenic mice revealed no hippocampally mediated memory impairment. Significant atrophy in most cortical areas due solely to TDP-43 expression indicates that this mouse model remains useful for providing critical insight into co-occurrence of TDP-43 pathology, neurodegeneration, and behavioral deficits in FTLD.SIGNIFICANCE STATEMENT The tTA expression system has been widely used in mice to model neurological disorders. The technique allows investigators to reversibly turn on or off disease causing genes. Here, we report on a mouse model that overexpresses human TDP-43 using tTA and attempt to recapitulate features of TDP-43 pathology present in human FTLD. The tTA expression system is problematic, resulting in dramatic degeneration of the hippocampus. Thus, our study adds a note of caution for the use of the tTA system. However, because FTLD is primarily characterized by cortical degeneration and our mouse model shows significant atrophy in most cortical areas due to human TDP-43 overexpression, our animal model remains useful for providing critical insight on this human disease.

Funding information:
  • NIGMS NIH HHS - GM30998(United States)

Early sensory experience influences the development of multisensory thalamocortical and intracortical connections of primary sensory cortices.

  • Henschke JU
  • Brain Struct Funct
  • 2017 Nov 3

Literature context:


Abstract:

The nervous system integrates information from multiple senses. This multisensory integration already occurs in primary sensory cortices via direct thalamocortical and corticocortical connections across modalities. In humans, sensory loss from birth results in functional recruitment of the deprived cortical territory by the spared senses but the underlying circuit changes are not well known. Using tracer injections into primary auditory, somatosensory, and visual cortex within the first postnatal month of life in a rodent model (Mongolian gerbil) we show that multisensory thalamocortical connections emerge before corticocortical connections but mostly disappear during development. Early auditory, somatosensory, or visual deprivation increases multisensory connections via axonal reorganization processes mediated by non-lemniscal thalamic nuclei and the primary areas themselves. Functional single-photon emission computed tomography of regional cerebral blood flow reveals altered stimulus-induced activity and higher functional connectivity specifically between primary areas in deprived animals. Together, we show that intracortical multisensory connections are formed as a consequence of sensory-driven multisensory thalamocortical activity and that spared senses functionally recruit deprived cortical areas by an altered development of sensory thalamocortical and corticocortical connections. The functional-anatomical changes after early sensory deprivation have translational implications for the therapy of developmental hearing loss, blindness, and sensory paralysis and might also underlie developmental synesthesia.