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Neuroaktywne steroidy i neurosteroidy w mechanizmach depresji i zaburzeń lękowych oraz ich możliwy potencjał terapeutyczny
2018-08-20

Neuroactive steroids and neurosteroids in the mechanisms of depression and anxiety disorders: Potential therapeutic opportunities in depression and anxiety disorders

Hormonal steroids synthesized in the adrenals and gonads, neurosteroids synthesized in the brain and synthetic or egzogenous steroids belong to the group of neuroactive steroids. They have the ability to modulate the central and peripheral nervous system and play a crucial role in many physiological and pathophysiological states. Neurosteroids are potent and effective neuromodulators that are synthesized from cholesterol in the CNS. These agents and their synthetic derivatives influence the function of multiple signaling pathways including receptors for γ-aminobutyric acid (GABA) and glutamate, the major inhibitory and excitatory neurotransmitters in the central nervous system (CNS). However, they also modulate sigma-1 receptors and they are modulated themselves by SSRIs. Both pre-clinical and clinical studies have shown that neurosteroid homeostasis is altered in depression and anxiety disorders and antidepressants may act in part through restoring neurosteroid disbalance. Thus, neurosteroids may constitute a novel therapeutic approach in the treatment of anxiolytic and depression disorders. Moreover, novel drugs interfering with neurosteroidogenesis such as ligands of the translocator protein (18 kDa) may represent an attractive pharmacological option for novel anxiolytics and antidepressants which lack the unwarranted side effects of benzodiazepines. In this paper, we review the mechanisms of neurosteroid action in brain with an emphasis on those neurosteroids that potently modulate the function of GABAA receptors. We then discuss evidence indicating a role for neurosteroids in anxiety and depression disorders, and focus on potential strategies that can be used to manipulate CNS neurosteroid synthesis and function for therapeutic purposes.

Keywords: stress, anxiety, depression, neurosteroids, neuroactive steroids, GABAA receptor, sigma-1 receptor, serotonin transporter, TSPO

© Farm Pol, 2018, 74 (8): 460–485