Neurosteroids, stress and depression: Potential therapeutic opportunities

NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS

卷:37

Review

Zorumski, Charles F.^1,2  Paul, Steven M.^4,5,6  Izumi, Yukitoshi¹  Covey, Douglas F.³  Mennerick, Steven^1,2 

[1] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA

[2] Washington Univ, Sch Med, Dept Neurobiol, St Louis, MO 63110 USA

[3] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63110 USA

[4] Cornell Univ, Dept Neurol, Weill Cornell Med Coll, New York, NY 10021 USA

[5] Cornell Univ, Dept Psychiat, Weill Cornell Med Coll, New York, NY 10021 USA

[6] Cornell Univ, Dept Pharmacol, Weill Cornell Med Coll, New York, NY 10021 USA

关键词: Neurosteroids;    Neuroactive steroids;    Allopregnanolone;    Stress;    Depression;    Anxiety;    Hippocampus;   

DOI  :  10.1016/j.neubiorev.2012.10.005

来源: Elsevier

【 摘 要 】

Neurosteroids are potent and effective neuromodulators that are synthesized from cholesterol in the brain. These agents and their synthetic derivatives influence the function of multiple signaling pathways including receptors for gamma-aminobutyric acid (GABA) and glutamate, the major inhibitory and excitatory neurotransmitters in the central nervous system (CNS). Increasing evidence indicates that dysregulation of neurosteroid production plays a role in the pathophysiology of stress and stress-related psychiatric disorders, including mood and anxiety disorders. In this paper, we review the mechanisms of neurosteroid action in brain with an emphasis on those neurosteroids that potently modulate the function of GABA(A) receptors. We then discuss evidence indicating a role for GABA and neurosteroids in stress and depression, and focus on potential strategies that can be used to manipulate CNS neurosteroid synthesis and function for therapeutic purposes. (c) 2012 Elsevier Ltd. All rights reserved.

【 授权许可】

Free