Neuronal circuit-dependent alterations in expression of two isoforms of glutamic acid decarboxylase in the hippocampus following electroconvulsive shock: A stereology-based study.
There is an increasing body of evidence suggesting that GABAergic dysfunction is involved in various psychiatric disorders. The goal of our study was to investigate the influences of electroconvulsive therapy (ECT), one of the most effective treatments for depression, on the GABAergic system in the hippocampus. In this stereology-based study, we identified GABAergic neurons by immunostaining for two isoforms of glutamic acid decarboxylase (GAD), GAD65, and GAD67 and estimated the expression changes induced by single or repeated electroconvulsive shock (ECS; an animal model of ECT). The numerical density (ND) of entire population of GABAergic neurons (expressing GAD65 and/or GAD67) was seldom altered by the administration of ECS. GAD67-positive (GAD67(+)) neurons were also rarely affected by ECS. On the other hand, the ND of GAD65(+) neurons was changed in a layer-specific manner. In the CA1 region, the ND of GAD65(+) neurons was increased in the strata radiatum/lacunosum-moleculare (SR/SLM) by repeated ECS. In the CA3 region, the ND of GAD65(+) neurons was decreased in the stratum oriens and SR/SLM after single ECS. The expression ratio of GAD65 in GABAergic neurons was increased specifically in layers receiving afferents from the entorhinal cortex (EC), i.e., SR/SLM of the CA1 region and molecular layer of the dentate gyrus (DG), after repeated ECS administration, whereas the expression ratio of GAD67 in GABAergic neurons was decreased in several layers by the same treatment. These results indicate that the ECS-induced changes in ND of GAD65(+) or GAD67(+) neurons were most likely due to alterations in GAD expression rather than actual increases or decreases in cell numbers. Altogether, the neuronal circuit-dependent alterations in GABA-mediated signaling may play a contributory role in the depression treatment process introduced by ECT.
Jinno
Shozo
S
Department of Anatomy and Neurobiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. sjnno@med.kyushu-u.ac.jp
Kosaka
Toshio
T
D000704:Analysis of Variance; D000818:Animals; D004597:Electroshock / Q000379:methods*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D005968:Glutamate Decarboxylase / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology* / Q000201:enzymology*; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000201:enzymology*; D013238:Stereotaxic Techniques; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2