Sex difference in sensitivity to allopregnanolone neuroprotection in mice correlates with effect on spontaneous inhibitory post synaptic currents

NEUROPHARMACOLOGY

卷:61

Article

Kelley, Melissa H.¹  Kuroiwa, Masayuki¹  Taguchi, Noriko¹  Herson, Paco S.¹ 

[1] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA

关键词: Allopregnanolone;    GABA(A) receptor;    Purkinje cell;    Sex difference;    Ischemia;    Neuroprotection;   

DOI  :  10.1016/j.neuropharm.2011.05.017

来源: Elsevier

【 摘 要 】

Allopregnanolone (ALLO) is a neurosteroid that has many functions in the brain, most notably neuroprotection and modulation of gamma-amino butyric acid (GABA) neurotransmission. Using a mouse model of cardiac arrest and cardiopulmonary resuscitation, we have previously demonstrated that ALLO protects cerebellar Purkinje cells (PCs) from ischemia in a GABA(A) receptor-dependent manner. In this study we examined the effect of sex on ALLO neuroprotection, observing that low dose ALLO (2 mg/kg) provided greater neuroprotection in females compared to males. At a higher dose of ALLO (8 mg/kg), both sexes were significantly protected from ischemic damage. Using an acute cerebellar slice preparation, whole cell voltage clamp recordings were made from PCs. Spontaneous inhibitory post synaptic currents (IPSCs) were analyzed and the response to physiological ALLO (10 nM) was significantly greater in female PCs compared to male. In contrast, recordings of miniature IPSCs, did not exhibit a sex difference in response to ALLO, suggesting that ALLO affects males and females differentially through a mechanism other than binding postsynaptic GABA(A) receptors. We conclude that the female brain has greater sensitivity to ALLO mediated potentiation of GABAergic neurotransmission, contributing to increased neuroprotection. (C) 2011 Elsevier Ltd. All rights reserved.

【 授权许可】

Free