Ethanol Stimulates Endoplasmic Reticulum Inositol Triphosphate and Sigma Receptors to Promote Withdrawal-Associated Loss of Neuron-Specific Nuclear Protein/Fox-3
Autor: | Mark A. Prendergast, Anna R. Reynolds, Meredith A. Saunders |
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Rok vydání: | 2016 |
Předmět: |
Male
0301 basic medicine medicine.medical_specialty Macrocyclic Compounds medicine.drug_class Inositol Phosphates Medicine (miscellaneous) Nerve Tissue Proteins Hippocampal formation Endoplasmic Reticulum Toxicology Hippocampus Article Calcium in biology 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Animals Receptors sigma Receptor Oxazoles Ethanol biology Dentate gyrus Endoplasmic reticulum Antigens Nuclear Ethylenediamines Receptor antagonist Rats Substance Withdrawal Syndrome Psychiatry and Mental health 030104 developmental biology medicine.anatomical_structure Endocrinology nervous system biology.protein Female Neuron NeuN 030217 neurology & neurosurgery |
Zdroj: | Alcoholism: Clinical and Experimental Research. 40:1454-1461 |
ISSN: | 0145-6008 |
Popis: | Background Prior studies demonstrate that ethanol (EtOH) exposure induces the release of intracellular calcium (CA2+) in modulation of γ-aminobutyric acid-ergic tone and produces concomitant alterations in sigma (σ)-1 protein expression that may contribute to the development EtOH dependence. However, the influence of CA2+ released from endoplasmic reticulum (ER)-bound inositol triphosphate (IP3) and σ-1 receptors in regulating hippocampal function has yet to be delineated. Methods Rat hippocampal explants were subjected to chronic intermittent EtOH (CIE) exposure with or without the addition of IP3 inhibitor xestospongin C (0 to 0.5 μM) or σ-1 receptor antagonist BD-1047 (0 to 80 μM). Hippocampal viability was assessed via immunohistochemical labeling of neuron-specific nuclear protein (NeuN)/Fox-3 in CA1, CA3, and dentate gyrus (DG) subregions. Results Exposure to CIE produced consistent and significant decreases of NeuN/Fox-3 in each primary cell layer of the hippocampal formation. Co-exposure to xestospongin reversed these effects in the CA1 subregion and significantly attenuated these effects in the CA3 and DG regions. Xestospongin application also significantly increased NeuN/Fox-3 immunofluorescence in EtOH-naive hippocampi. Co-exposure to 20 μM BD-1047 also reversed the loss of NeuN/Fox-3 during CIE exposure in each hippocampal cell layer, whereas exposure to 80 μM BD-1047 did not alter NeuN/Fox-3 in EtOH-treated hippocampi. By contrast, 80 μM BD-1047 application significantly increased NeuN/Fox-3 immunofluorescence in EtOH-naive hippocampi in each subregion. Conclusions These data suggest that EtOH stimulates ER IP3 and σ-1 receptors to promote hippocampal loss of NeuN/Fox-3 during CIE. |
Databáze: | OpenAIRE |
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