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Publication

Regulation of morphine-induced synaptic alterations: Role of oxidative stress, ER stress, and autophagy.

The Journal of cell biology | 2016

Our findings suggest that morphine dysregulates synaptic balance in the hippocampus, a key center for learning and memory, via a novel signaling pathway involving reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, and autophagy. We demonstrate in this study that exposure of morphine to hippocampal neurons leads to a reduction in excitatory synapse densities with a concomitant enhancement of inhibitory synapse densities via activation of the μ opioid receptor. Furthermore, these effects of morphine are mediated by up-regulation of intracellular ROS from NADPH oxidase, leading, in turn, to sequential induction of ER stress and autophagy. The detrimental effects of morphine on synaptic densities were shown to be reversed by platelet-derived growth factor (PDGF), a pleiotropic growth factor that has been implicated in neuroprotection. These results identify a novel cellular mechanism involved in morphine-mediated synaptic alterations with implications for therapeutic interventions by PDGF.

Pubmed ID: 27810915 RIS Download

Research resources used in this publication

Additional research tools detected in this publication

Antibodies used in this publication

Associated grants

Agency: NIGMS NIH HHS, United States
Id: P30 GM103509
Agency: NIDA NIH HHS, United States
Id: R01 DA033150
Agency: NINDS NIH HHS, United States
Id: R01 NS077873

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This is a list of tools and resources that we have found mentioned in this publication.

Novus Biologicals (tool)

RRID:SCR_004286

Commercial antibody vendor which supplies antibodies and other products to life science researchers.

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Synaptic Systems (tool)

RRID:SCR_013612

An Antibody supplier

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C57BL/6N (tool)

RRID:MGI:2159965

laboratory mouse with name C57BL/6N from MGI.

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SD (tool)

RRID:RGD_70508

Rattus norvegicus with name SD from RGD.

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Glutamic acid decarboxylase; GAD antibody - Gottlieb, D.I.; Washington University School of Medicine (antibody)

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This monoclonal targets GAD65

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Goat Anti-Guinea Pig IgG (H+L) Highly Cross-adsorbed Antibody, Alexa Fluor ?? 488 Conjugated (antibody)

RRID:AB_2534117

This unknown targets Guinea Pig IgG (H+L)

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Goat anti-Mouse IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 555 (antibody)

RRID:AB_2535845

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Anti-PSD95 antibody (antibody)

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Guinea pig Anti-Vesicular Glutamate Transporter 1 (VGLUT1) Polyclonal antibody, Unconjugated (antibody)

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Mouse Anti-Gephyrin Monoclonal Antibody, Unconjugated, Clone 45 (antibody)

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Rabbit anti-Guinea Pig IgG (H+L) Secondary Antibody, HRP (antibody)

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goat anti-rabbit IgG-HRP (antibody)

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This polyclonal targets goat anti-rabbit IgG-HRP

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This polyclonal targets Mouse IgG

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Anti-β-Actin antibody, Mouse monoclonal (antibody)

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This monoclonal targets β-Actin

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LC3B Antibody (antibody)

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This polyclonal targets LC3B

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MBL International Corporation P62/SQSTM1 100 UL (antibody)

RRID:AB_2571590

This polyclonal targets

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ATG5 Antibody (antibody)

RRID:AB_828587

This unknown targets ATG5

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BECN1 (H-300) (antibody)

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This polyclonal targets BECN1

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This polyclonal targets ATF6

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IRE1alpha (H-190) (antibody)

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This polyclonal targets IRE1alpha (H-190)

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PERK (H-300) (antibody)

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This polyclonal targets EIF2AK3

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Rabbit Anti-PERK, phospho (Thr981) Polyclonal Antibody, Unconjugated (antibody)

RRID:AB_2293243

This polyclonal targets EIF2AK3

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Mouse Anti-BiP Monoclonal Antibody, Unconjugated, Clone 40 (antibody)

RRID:AB_398291

This monoclonal targets BiP

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GAD65 Antibody (antibody)

RRID:AB_10004060

This polyclonal targets GAD65

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Rabbit antibody to ATG7: whole serum (antibody)

RRID:AB_2492996

This unknown targets A synthetic peptide (DSTRDRTLDQQC) corresponding to the C-terminal of human APG7 protein conjugated to blue carrier protein has been used as the immunogen. The peptide is homologous with the corresponding sequence derived from APG7 protein in mouse, rat, S. cerevisiae, Macaca mulatta (monkey) and Canis familiaris (dog).

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Imaris (software resource)

RRID:SCR_007370

Imaris provides range of capabilities for working with three dimensional images. Uses flexible editing and processing functions, such as interactive surface rendering and object slicing capabilities. And output to standard TIFF, Quicktime and AVI formats. Imaris accepts virtually all image formats that are used in confocal microscopy and many of those used in wide-field image acquisition.

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