TY - JOUR
T1 - Betaine attenuates memory impairment after water-immersion restraint stress and is regulated by the GABAergic neuronal system in the hippocampus
AU - Kunisawa, Kazuo
AU - Kido, Kiwamu
AU - Nakashima, Natsuki
AU - Matsukura, Takuya
AU - Nabeshima, Toshitaka
AU - Hiramatsu, Masayuki
N1 - Publisher Copyright:
© 2016 Elsevier B.V.
PY - 2017
Y1 - 2017
N2 - GABA mediated neuronal system regulates hippocampus-dependent memory and stress responses by controlling plasticity and neuronal excitability. Here, we demonstrate that betaine ameliorates water-immersion restraint stress (WIRS)-induced memory impairments. This improvement was inhibited by a betaine/GABA transporter-1 (GABA transporter-2: GAT2) inhibitor, NNC 05–2090. In this study, we investigated whether memory amelioration by betaine was mediated by the GABAergic neuronal system. Adult male mice were co-administered betaine and GABA receptor antagonists after WIRS. We also examined whether memory impairment after WIRS was attenuated by GABA receptor agonists. The memory functions were evaluated using a novel object recognition test 3–6 days after WIRS and/or the step-down type passive avoidance test at 7–8 days. The co-administration of the GABAAreceptor antagonist bicuculline (1 mg/kg) or the GABABreceptor antagonist phaclofen (10 mg/kg) 1 h after WIRS suppressed the memory-improving effects induced by betaine. Additionally, the administration of the GABAAreceptor agonist muscimol (1 mg/kg) or the GABABreceptor agonist baclofen (10 mg/kg) 1 h after WIRS attenuated memory impairments. These results were similar to the data observed with betaine. The treatment with betaine after WIRS significantly decreased the expression of GABA transaminase, and this effect was partially blocked by NNC 05–2090 in the hippocampus. WIRS caused a transient increase in hippocampal GABA levels and the changes after WIRS were not affected by betaine treatment in an in vivo microdialysis study. These results suggest that the beneficial effects of betaine may be mediated in part by changing the GABAergic neuronal system.
AB - GABA mediated neuronal system regulates hippocampus-dependent memory and stress responses by controlling plasticity and neuronal excitability. Here, we demonstrate that betaine ameliorates water-immersion restraint stress (WIRS)-induced memory impairments. This improvement was inhibited by a betaine/GABA transporter-1 (GABA transporter-2: GAT2) inhibitor, NNC 05–2090. In this study, we investigated whether memory amelioration by betaine was mediated by the GABAergic neuronal system. Adult male mice were co-administered betaine and GABA receptor antagonists after WIRS. We also examined whether memory impairment after WIRS was attenuated by GABA receptor agonists. The memory functions were evaluated using a novel object recognition test 3–6 days after WIRS and/or the step-down type passive avoidance test at 7–8 days. The co-administration of the GABAAreceptor antagonist bicuculline (1 mg/kg) or the GABABreceptor antagonist phaclofen (10 mg/kg) 1 h after WIRS suppressed the memory-improving effects induced by betaine. Additionally, the administration of the GABAAreceptor agonist muscimol (1 mg/kg) or the GABABreceptor agonist baclofen (10 mg/kg) 1 h after WIRS attenuated memory impairments. These results were similar to the data observed with betaine. The treatment with betaine after WIRS significantly decreased the expression of GABA transaminase, and this effect was partially blocked by NNC 05–2090 in the hippocampus. WIRS caused a transient increase in hippocampal GABA levels and the changes after WIRS were not affected by betaine treatment in an in vivo microdialysis study. These results suggest that the beneficial effects of betaine may be mediated in part by changing the GABAergic neuronal system.
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U2 - 10.1016/j.ejphar.2016.12.007
DO - 10.1016/j.ejphar.2016.12.007
M3 - Article
C2 - 27940054
AN - SCOPUS:85007140049
SN - 0014-2999
VL - 796
SP - 122
EP - 130
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
ER -