Down-Regulated GABAergic Expression in the Olfactory Bulb Layers of the Mouse Deficient in Monoamine Oxidase B and Administered With Amphetamine

Abstract

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-knockout (KO) mice after receiving repeated intraperitoneal injections (2 doses/day, total 7 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 downregulated 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.

GABA synthesis in Schwann cells is induced by the neuroactive steroid allopregnanolone

“…This mechanism might explain the increased GAD67 expression as the bioinformatic analysis revealed several CRE elements in the promoter region upstream of the GAD67 transcription start site. Our data supported a direct relationship between CREB and GAD, as recently showed by Yin et al (2009), who reported that decreased phosphorylation of CREB is responsible for amphetamine-induced inhibition of GAD67 expression in the olfactory bulb. However, we cannot disregard the evidence of Murphy and Segal (2000) who demonstrated an indirect correlation between CREB phospholylation and GAD expression.…”

Body Weight-Supported Treadmill Training Ameliorates Motoneuronal Hyperexcitability by Increasing GAD-65/67 and KCC2 Expression via TrkB Signaling in Rats with Incomplete Spinal Cord Injury

“…The establishment and modulation of GABAergic inhibitory neuronal circuits in the CNS of rodents may be aided by BDNF-TrkB signaling [ 22 , 48 – 50 ]. Using the signaling of Ras/ERK (one of the TrkB signaling cascades), BDNF/TrkB can potentially stimulate p-CREB activation of the GAD-65 promoter (5.5-kb 5' GAD65-luc construct) and regulatory zones in cortical inhibitory interneurons, and the level of GAD-67 might be mediated through p-CREB within olfactory bulb cells [ 48 , 51 ]. Furthermore, via modulating the PLC-1 and Shc cascade after SCI, BDNF-TrkB signaling can upregulate KCC2 expression, reducing spasticity and neuropathic pain [ 20 , 42 ].…”

Exercise training modulates glutamic acid decarboxylase-65/67 expression through TrkB signaling to ameliorate neuropathic pain in rats with spinal cord injury

“…38,50 Sa´nchez-Huertas et al 40 found that BDNF/ TrkB could promote p-CREB activating of the GAD65 promoter (5.5-kb 5' GAD65-luc construct) and regulatory regions through Ras/ERK signaling (one of the TrkB signaling cascades) in cortical inhibitory interneurons. Yin et al 51 found that the GAD-67 level may be regulated by p-CREB in olfactory bulb cells. However, the mechanism of the p-CREB promoting the GAD-67 synthesis needs further study.…”

“…Yin et al. 51 found that the GAD-67 level may be regulated by p-CREB in olfactory bulb cells. However, the mechanism of the p-CREB promoting the GAD-67 synthesis needs further study.…”