A-Kinase Anchoring Protein 150 and Protein Kinase A Complex in the Basolateral Amygdala Contributes to Depressive-like Behaviors Induced by Chronic Restraint Stress
| Autor: | Fang Wang, Jun-Feng Xu, Hai-Yun Zhou, Qian-Qian Cui, Jian-Guo Chen, Peng-Fei Wu, Shi-Ge Xue, Jin-Gang He, Li-Hong Long, Bin Zhou, Shuang-Qi Gao, Zhuang-Li Hu |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
A-kinase-anchoring protein Restraint Physical A Kinase Anchor Proteins AMPA receptor Neurotransmission Synaptic Transmission Small hairpin RNA 03 medical and health sciences Mice 0302 clinical medicine medicine Animals Receptors AMPA Protein kinase A Biological Psychiatry Swimming Chemistry Basolateral Nuclear Complex Depression Glutamate receptor Proteins Cyclic AMP-Dependent Protein Kinases Cell biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Hindlimb Suspension Excitatory postsynaptic potential 030217 neurology & neurosurgery Stress Psychological Basolateral amygdala |
| Zdroj: | Biological psychiatry. 86(2) |
| ISSN: | 1873-2402 |
| Popis: | Background The basolateral amygdala (BLA) has been widely implicated in the pathophysiology of major depressive disorder. A-kinase anchoring protein 150 (AKAP150) directs kinases and phosphatases to synaptic glutamate receptors, controlling synaptic transmission and plasticity. However, the role of the AKAP150 in the BLA in major depressive disorder remains poorly understood. Methods Depressive-like behaviors in C57BL/6J mice were developed by chronic restraint stress (CRS). Mice received either intra-BLA injection of lentivirus-expressing Akap5 short hairpin RNA or Ht-31, a peptide to disrupt the interaction of AKAP150 and protein kinase A (PKA), followed by depressive-like behavioral tests. Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid glutamate receptor (AMPAR)–mediated miniature excitatory postsynaptic currents were recorded by whole-cell patch-clamp techniques. Results Chronic stress exposure induced depressive-like behaviors, which were accompanied by an increase in total and synaptic AKAP150 expression in the BLA. Accordingly, CRS facilitated the association of AKAP150 with PKA, but not of calcineurin in the BLA. Intra-BLA infusion of lentivirus-expressing Akap5 short hairpin RNA or Ht-31 prevented depressive-like behaviors and normalized phosphorylation of serine 845 and surface expression of AMPAR subunit 1 (GluA1) in the BLA of CRS mice. Finally, blockage of AKAP150-PKA complex signaling rescued the changes in AMPAR-mediated miniature excitatory postsynaptic currents in depressive-like mice. Conclusions These results suggest that AKAP150-PKA directly modulates BLA neuronal synaptic strength, and that AKAP150-PKA-GluA1 streamline signaling complex is responsible for CRS-induced disruption of synaptic AMPAR-mediated transmission and depressive-like behaviors in mice. |
| Databáze: | OpenAIRE |
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