Down-regulated GABAergic expression in the olfactory bulb layers of the mouse deficient in monoamine oxidase B and administered with amphetamine.
This study explores primarily the role of the activity of monoamine oxidase B (MAOB) in the regulation of glutamic acid decarboxylase(67) (GAD(67)) expression in distinct layers of main olfactory bulb (OlfB), which links the limbic system. Moreover, the response of GAD(67) was investigated to amphetamine perturbation in the absence of MAOB activity. Immunocytochemical analysis was performed on OlfB sections prepared from the adult wild type (WT) and the MAOB gene-knocked-out (KO) mice after receiving repeated intraperitoneal injections (two doses per day, total seven doses) of saline or amphetamine, 5 mg/kg. The levels of the GAD(67) immunoreactivity were approximate 25 and 38% lower in respective glomerular (GloL) and mitral cell layers (ML) of saline-treated KO mice than that of WT, whereas similar in the external plexiform or granule cell layers (GraL) of the KO and WT. In the GloL, the level of tyrosine hydroxylase was 39% lower in the KO mice than WT, implicating different dopamine content in the KO from WT. The amphetamine exposure down-regulated the levels of GAD(67) in the WT layers by 46 to 52%, and in KO layers 65 to 71%, except ML. The GraL GAD(67) level may be regulated by the activation of CREB, as the phosphorylated (p) CREB coexisted with GAD(67), and the percentage of GAD(67)-expressing pCREB neurons was decreased by the amphetamine exposure. The data indicate that the activity of MAOB could modulate the regular and amphetamine-perturbed expression of GAD(67) and pCREB. Thus, interactions are suggested among the MAOB activity, GABA content of OlfB, and olfaction.
Yin
Hsiang-Shu
HS
Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, 100, Taiwan, ROC. hsyin@ntu.edu.tw
Chen
Kevin
K
Shih
Jean C
JC
Tien
Tai-Wei
TW
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D015536:Down-Regulation; D005968:Glutamate Decarboxylase / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008995:Monoamine Oxidase / Q000235:genetics / Q000378:metabolism*; D009830:Olfactory Bulb / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000697:Central Nervous System Stimulants; D017362:Cyclic AMP Response Element-Binding Protein; D007527:Isoenzymes; D005680:gamma-Aminobutyric Acid; D000661:Amphetamine; D008995:Monoamine Oxidase; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1