Attenuation of γ-aminobutyric acid (GABA) transaminase activity contributes to GABA increase in the cerebral cortex of mice exposed to β-cypermethrin.
The current study investigated the γ-aminobutyric acid (GABA) levels and GABA metabolic enzymes (GABA transaminase (GABA(T)) and glutamate decarboxylase (GAD)) activities at 2 and 4 h after treatment, using a high-performance liquid chromatography with ultraviolet detectors and colorimetric assay, in the cerebral cortex of mice treated with 20, 40 or 80 mg/kg β-cypermethrin by a single oral gavage, with corn oil as vehicle control. In addition, GABA protein (4 h after treatment), GABA(T) protein (2 h after treatment) and GABA receptors messenger RNA (mRNA) expression were detected by immunohistochemistry, Western blot and real-time quantitative reverse transcriptase polymerase chain reaction, respectively. β-Cypermethrin (80 mg/kg) significantly increased GABA levels in the cerebral cortex of mice, at both 2 and 4 h after treatment, compared with the control. Also, GABA immunohistochemistry results suggested that the number of positive granules was increased in the cerebral cortex of mice 4 h after exposure to 80 mg/kg β-cypermethrin when compared with the control. Furthermore, the results also showed that GABA(T) activity detected was significantly decreased in the cerebral cortex of mice 2 h after β-cypermethrin administration (40 or 80 mg/kg). No significant changes were found in GAD activity, or the expression of GABA(T) protein and GABAB receptors mRNA, in the cerebral cortex of mice, except that 80 mg/kg β-cypermethrin caused a significant decrease, compared with the vehicle control, in GABAA receptors mRNA expression 4 h after administration. These results suggested that attenuated GABA(T) activity induced by β-cypermethrin contributed to increased GABA levels in the mouse brain. The downregulated GABAA receptors mRNA expression is most likely a downstream event.
1School of Public Health, China Medical University, Shenyang, China.
Y
Y
Han
D
D
Cao
X
X
Li
R
R
Zhang
F
F
Yu
Y
Y
Ren
L
L
An
D000612:4-Aminobutyrate Transaminase / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism; D007150:Immunohistochemistry; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D051379:Mice; D011722:Pyrethrins / Q000633:toxicity*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018079:Receptors, GABA / Q000096:biosynthesis / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D007306:Insecticides; D011722:Pyrethrins; D012333:RNA, Messenger; D018079:Receptors, GABA; C017160:cypermethrin; D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase; D005968:Glutamate Decarboxylase
glutamate decarboxylase; β-Cypermethrin; γ-aminobutyric acid; γ-aminobutyric acid receptors; γ-aminobutyric acid transaminase