<strong>Allopregnanolone as a New Therapeutic Target for Depression and Anxiety</strong>

Abstract

Abstract:Allopregnanolone-the neurosteroid is synthetized from cholesterol via TSPO mediated transfer from outer mitochondrial membrane to inner mitochondrial membrane. Recent study showed reduced level of neurosteroids represented by allopregnanolone were involved in the occurrence and development process of many mental disorders including anxiety and depression. Moreover，exogenous allopregnanolone treatment can significantly improve the anxious and depressive symptoms. The mechanisims underlying the antidepressant and anxiolytic effects of allopregnanolone were considered mainly to be associated with its positive activation on GABAA receptor. In addition，allopregnanolone played an important role in regulating functions of HPA axis as well as stimulating neurogenesis. This review described the production process of allopregnanalone，its role in anxiety and depression and its possible mechanisms of treatment effects.

Key words:allopregnanolone,anxiety,depression,&,gamma,-aminobutyric acid A receptor,hypothalamus-hypophysis-adrenal axis,nerve regeneration

CLC Number:

R964

JIANG Xiang-yun, SHANG Chao, LI Lei, SUN Shu-zheng, LI Yun-feng, WANG Heng-lin.Allopregnanolone as a New Therapeutic Target for Depression and Anxiety[J]. ACTA NEUROPHARMACOLOGICA, 2016, 6(2): 26-30.

References

[1]Mariana Rey, Hector Coirini. Synthetic neurosteroids on brain protection[J]. Neural Regeneration Research, 2015, 10(1):17-21.

[2]Roberto Cosimo Melcangi, Ayikoe Guy Mensah-Nyagan. Neurosteroids: measurement and pathophysiologic relevance[J]. Neurochemistry International, 2008, 52(4–5):503-505.

[3]Cornelius Schüle, Caroline Nothdurfter, Rainer Rupprecht. The role of allopregnanolone in depression and anxiety[J]. Progress in Neurobiology, 2014, 113(3):79-87.

[4]Anjana Bali, Amteshwar Singh Jaggi. Multifunctional aspects of allopregnanolone in stress and related disorders[J]. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 2014, 48(42):64-78.

[5]Schumacher M, Mattern C, Ghoumari A, et al. Revisiting the roles of progesterone and allopregnanolone in the nervous system: Resurgence of the progesterone receptors[J]. Progress in Neurobiology, 2014, 113(1):6-39.

[6]Cornelius Schüle, Eser D, Thomas C Baghai, et al. Neuroactive steroids in affective disorders: target for novel antidepressant or anxiolytic drugs?[J]. Neuroscience, 2011, 191:55-77.

[7]Caroline Nothdurfter, Thomas C Baghai, Cornelius Schüle, et al. Translocator protein (18 kDa) (TSPO) as a therapeutic target for anxiety and neurologic disorders[J]. European Archives of Psychiatry and Clinical Neuroscience, 2012, 262 Suppl 2(2):107-112.

[8]Rainer Rupprecht, Vassilios Papadopoulos, Gerhard Rammes, et al. Translocator protein (18 kDa) (TSPO) as a therapeutic target for neurological and psychiatric disorders[J]. Nature Reviews Drug Discovery, 2010, 9(12):971-988.

[9]Zheng Ping. Neuroactive steroid regulation of neurotransmitter release in the CNS: action, mechanism and possible significance[J]. Progress in Neurobiology, 2009, 89(2):134-152.

[10]Veska Uzunova, Aileen S Wrynn, Anu Kinnunen, et al. Chronic antidepressants reverse cerebrocortical allopregnanolone decline in the olfactory-bulbectomized rat[J]. European J Pharmacology, 2004, 486(1):31-34.

[11]Kinzo Matsumoto, Giulia Puia, Erbo Dong, et al. GABA(A) receptor neurotransmission dysfunction in a mouse model of social isolation-induced stress: possible insights into a non-serotonergic mechanism of action of SSRIs in mood and anxiety disorders[J]. Stress-the International Journal on the Biology of Stress, 2007, 10(1):3-12.

[12]Yukihiko Shirayama, Andrew C H Chen, Shin Nakagawa, et al. Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression[J]. J Neuroscience the Official Journal of the Society for Neuroscience, 2002, 22(8):3251-3261.

[13]Erbo Dong, Kinzo Matsumoto, Veska Uzunova, et al. Brain 5alpha-dihydroprogesterone and allopregnanolone synthesis in a mouse model of protracted social isolation[J]. Proceedings of the National Academy of Sciences, 2001, 98(5):2849-2854.

[14]Laura Mòdol, Sonia Darbra, Marc Pallarès. Neurosteroids infusion into the CA1 hippocampal region on exploration, anxiety-like behaviour and aversive learning[J]. Behavioural Brain Research, 2011, 222(1):223-229.

[15]Francesca Brambilla, Carmen Mellado, Alessandra Alciati, et al. Plasma concentrations of anxiolytic neuroactive steroids in men with panic disorder[J]. Psychiatry Research, 2005, 135(3):185-190.

[16]Singh A, Kumar A. Possible GABAergic modulation in the protective effect of allopregnanolone on sleep deprivation-induced anxiety-like behavior and oxidative damage in mice[J]. Methods & Findings in Experimental & Clinical Pharmacology, 2008, 30(9):681-709.

[17]Alicia A Walf, Kanako Sumida, Cheryl A Frye. Inhibiting 5alpha-reductase in the amygdala attenuates antianxiety and antidepressive behavior of naturally receptive and hormone-primed ovariectomized rats[J]. Psychopharmacology, 2006, 186 (3):302-311.

[18] Elif Engin, Dallas Treit. The anxiolytic-like effects of allopregnanolone vary as a function of intracerebral microinfusion site: the amygdala, medial prefrontal cortex, or hippocampus[J]. Behav Pharmacol, 2007, 18(5-6): 461–470.

[19]Frye C A, Paris J J. Progesterone turnover to its 5α-reduced metabolites in the ventral tegmental area of the midbrain is essential for initiating social and affective behavior and progesterone metabolism in female rats [J]. J Endocrinological Investigation, 2011, 34(7): e188-e199.

[20]杨红菊, 赵楠, 罗质璞. 神经类固醇对学习记忆与应激性情绪反应的调控作用[J]. 国际药学研究杂志, 2001, 28(3): 140-144.

[21]Follesa P, Porcu P, Sogliano C, et al. Changes in GABAA receptor gamma 2 subunit gene expression induced by long-term administration of oral contraceptives in rats[J]. Neuropharmacology, 2002, 42(3):325-336.

[22]Shirayama Y, Muneoka K, Fukumoto M, et al. Infusions of allopregnanolone into the hippocampus and amygdala, but not into the nucleus accumbens and medial prefrontal cortex, produce antidepressant effects on the learned helplessness rats[J]. Hippocampus, 2011, 21(10):1105-1113.

[23]刘畅, 张黎明, 杨卫星, 等. 18ku转位蛋白:焦虑症治疗的潜在新靶点[J]. 国际药学研究杂志, 2016, 43(2):229-233.

[24] Jane Evans, Sun Yu-hui, Ailsa Mcgregor, et al. Allopregnanolone regulates neurogenesis and depressive/anxiety-like behaviour in a social isolation rodent model of chronic stress[J]. Neuropharmacology, 2012, 63(8):1315-1326.

[25]李云峰, 杨明, 赵毅民,等. 巴戟天寡糖对皮质酮损伤的PC12细胞的保护作用[J]. 中国中药杂志, 2000, 25(9):551-554.

[26]Schüle C, Eser D, Baghai T C, et al. Neuroactive steroids in affective disorders: target for novel antidepressant or anxiolytic drugs?[J]. Neuroscience, 2011, 191: 55-77.

[27]Pierrick Poisbeau, Anne Florence Keller, Maya Aouad, et al. Analgesic strategies aimed at stimulating the endogenous production of allopregnanolone[J]. Frontiers in Cellular Neuroscience, 2014, 8(8):174-174.

[28]Bail Anjana, Amteshwar Singh Jaggi. Multifunctional aspects of allopregnanolone in stress and related disorders[J]. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 2014, 48(42): 64-78.

Allopregnanolone as a New Therapeutic Target for Depression and Anxiety

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles15

Recommended Articles

Metrics

[1]	XIE bin, HUANG Zhi-yuan, LIN Duo-duo, YANG Fu-long, XIE Yi-bin.Effect of Acupuncture Combined with Medicine on Depressive Symptoms of Alzheimer’s Disease[J]. ACTA NEUROPHARMACOLOGICA, 2020, 10(5): 5-8.
[2]	MO Cui-ying, LUO Guo-ping.Influence of Nimergoline Combined with Trasylin and Psychotherapy for Depression in Patients with Post-stroke Depression[J]. ACTA NEUROPHARMACOLOGICA, 2020, 10(2): 7-10.
[3]	DI Tong，ZHAO Zhi-jie，BAO Jin-feng.Preliminary Study on the Effect of Folic Acid on Anxiety-Like Behavior in Adult Mice Induced by Maternal Separation[J]. Acta Neuropharmacologica, 2019, 9(1): 6-12.
[4]	FU Zhi-jiang1，GAO Yun2，ZHANG Wei3，LIU Zong-chao1，4，ZHANG Hua-wen4，LIU Shi-gui1，HUANG Chen-yi1，GAO Yin5，GAO Hai-ming1.Effects and Mechanisms of Depression on Bone Fracture Healing in Rats[J]. Acta Neuropharmacologica, 2018, 8(6): 1-8.
[5]	FU Zhi-jiang1，LIU Yong1，GAO Yin1，ZHANG Wei2，GAO Yun2，LIU Zong-chao1*.Effects and Mechanisms of Depression on Bone Fracture Healing in Rats[J]. Acta Neuropharmacologica, 2018, 8(4): 5-6.
[6]	CHEN Ling1，CHENG Zi-juan2，JIN Ji3，LI Qing-yu1，WANG Gang 1.Inhibition of Phosphodiesterase-2 Activity in the Amygdala Produces Anxiolytic-Like Effects in Mice[J]. Acta Neuropharmacologica, 2018, 8(4): 8-9.
[7]	LIANG Jian-hui1,2*, LIANG hui2, CHENG tao1, LIU Xiao-yan1, Simon M.Y.Lee3, TANG Ben-qin3, WANG Xiu-fen3, CHEN Feng4,Andrew J. Lawrence4.Comorbidity of Anxiety and Depression Induced by Liang’s Contextual-Stress Box in Mice[J]. Acta Neuropharmacologica, 2018, 8(4): 44-45.
[8]	SUN Yi，TAN Bo，SU Rui-bin.Biased Ligand——Novel Paradigm for Opioid Analgesics[J]. Acta Neuropharmacologica, 2018, 8(2): 1-7.
[9]	LIN Zhi-bin.Pharmacological Progress of Ganoderma on Anti-aging and Anti-Alzheimer’s Disease[J]. Acta Neuropharmacologica, 2018, 8(1): 9-15.
[10]	ZAN Gui-ying，SUN Xiang，LI Qing-lin，LIU Jing-gen.Research Progress of the Role and Underlying Mechanism of Dynorphin/κ Opioid Receptor in the Development of Depression[J]. Acta Neuropharmacologica, 2018, 8(1): 54-64.
[11]	LIANG Hui，CHENG Tao，LIANG Jian-hui.Progress in the Comorbidity of Depression and Anxiety[J]. Acta Neuropharmacologica, 2017, 7(6): 30-35.
[12]	ZHANG Kuo，YANG Jing-yu，WU Chun-fu.Progress on Pathophysiology and Animal Models of Depression[J]. Acta Neuropharmacologica, 2017, 7(4): 8-16.
[13]	WAN Ye，GUO Chun-yan，LI Yong-min.Research Progress of Traditional Chinese Medicine in Parkinson’s Disease[J]. Acta Neuropharmacologica, 2017, 7(4): 36-42.
[14]	TIAN You，WANG Xue，AI Jing.Research Progress of Basal Forebrain Cholinergic Dysfunction in Alzheimer’s Disease[J]. Acta Neuropharmacologica, 2017, 7(4): 53-64.
[15]	REN Qian,WANG Zhen-zhen,CHEN Nai-hong.Regulation of Neuroplasticity by MicroRNA in Depression Disorder[J]. Acta Neuropharmacologica, 2017, 7(3): 12-20.