Pubertal hormones increase hippocampal expression of α4βδ GABAA receptors

NEUROSCIENCE LETTERS

卷:701

Article

Keating, Nicole^1,2  Zeak, Nicole¹  Smith, Sheryl S.¹ 

[1] Suny Downstate Med Ctr, Dept Physiol & Pharmacol, 450 Clarkson Ave, Brooklyn, NY 11203 USA

[2] Regeneron Pharmaceut, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA

关键词: Allopregnanolone;    alpha-4;    Delta;    Estradiol;    GABA(A) receptor;    CA1 hippocampus;   

DOI  :  10.1016/j.neulet.2019.02.005

来源: Elsevier

【 摘 要 】

CA1 hippocampal expression of alpha 4 beta delta GABA(A) receptors (GABARs) increases at the onset of puberty in female mice, an effect dependent upon the decline in hippocampal levels of the neurosteroid THP (3 alpha-OH-5 alpha-pregnan-20-one) which occurs at this time. The present study further characterized the mechanisms underlying alpha 4 beta delta expression, assessed in vivo. Blockade of pubertal levels of 17 beta-estradiol (E-2) (formestane, 0.5 mg/kg, i.p. 3 d) reduced alpha 4 and delta expression by 75-80% (P < 0.05) in CA1 hippocampus of female mice, assessed using Western blot techniques. Conversely, E-2 administration increased alpha 4 and delta expression by 50-100% in adults, an effect enhanced by more than 2-fold by concomitant administration of the 5 alpha-reductase blocker finasteride (50 mg/kg, i.p., 3d, P < 0.05), suggesting that both declining THP levels and increasing E-2 levels before puberty trigger alpha 4 beta delta expression. This effect was blocked by ICI 182,780 (20 mg/kg, s.c., 3 d), a selective blocker of E-2 receptor-alpha (ER-alpha). These results suggest that both the rise in circulating levels of E-2 and the decline in hippocampal THP levels at the onset of puberty trigger maximal levels of alpha 4 beta delta expression in the CA1 hippocampus.

【 授权许可】

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