NEUROACTIVE STEROIDS: FOCUS ON HUMAN BRAIN

被引:117
作者
Melcangi, R. C. [1 ]
Panzica, G. [2 ,3 ]
Garcia-Segura, L. M. [4 ]
机构
[1] Univ Milan, Dept Endocrinol Pathophysiol & Appl Biol, Ctr Excellence Neurodegenerat Dis, I-20133 Milan, Italy
[2] Univ Turin, Neuroendocrinol Lab, Dept Anat Pharmacol & Forens Med, Natl Inst Neurosci Italy INN,NIT, Turin, Italy
[3] NICO, I-10043 Turin, Italy
[4] CSIC, Inst Cajal, E-28002 Madrid, Spain
关键词
neurodegenerative disorders; mood disorders; GABA-A receptor; neurosteroids; GONADAL HORMONE REGULATION; DENDRITIC SPINE DENSITY; SEX-DIMORPHIC CHANGES; RAT ARCUATE NUCLEUS; DENTATE GYRUS; CELL-PROLIFERATION; SYNAPSE DENSITY; MESSENGER-RNA; RISK-FACTORS; ESTROGEN;
D O I
10.1016/j.neuroscience.2011.06.024
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Studies in experimental animals have revealed important roles of neuroactive steroids in the control of central nervous system functions during physiological and pathological conditions, suggesting that they may represent good candidates for the development of neuroprotective strategies for neurodegenerative and psychiatric disorders. Even if the characterization of the roles played by neuroactive steroids in humans is still at the beginning, several data are already available showing that they may be synthesized within the human CNS. Among the different enzymes, a prominent role is dedicated to aromatase that synthesizes estradiol whose neuroprotective effects have been described in experimental animals. Neuroactive steroid levels are modified by neurodegenerative conditions (i.e. Alzheimer's and Parkinson's diseases, multiple sclerosis) or in other mental diseases (i.e. schizophrenia), and may have an important role in physiological conditions, as the reorganization of grey and white matter during human puberty and adolescence or as a consequence of emotional responses. The interaction of some neuroactive steroids (i.e., allopregnanolone and isopregnanolone) with GABA-A receptor is particularly important in mood disorders. The presumptive role of estradiol and progesterone in neuroprotection is here discussed by comparing contradictory data that have been collected in humans. In conclusion, the state of the art of our knowledge of the role of neuroactive steroids in the normal and pathological human brain suggests several lines of future therapeutic developments in the treatments of neurological, neurodegenerative and affective disorders. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:1 / 5
页数:5
相关论文
共 83 条
[41]   Neuroactive steroids: State of the art and new perspectives [J].
Melcangi, R. C. ;
Garcia-Segura, L. M. ;
Mensah-Nyagan, A. G. .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2008, 65 (05) :777-797
[42]   Neuroactive steroids: Old players in a new game [J].
Melcangi, RC ;
Panzica, GC .
NEUROSCIENCE, 2006, 138 (03) :733-739
[43]   Gonadal steroids reduce the density of axospinous synapses in the developing rat arcuate nucleus: An electron microscopy analysis [J].
Mong, JA ;
Roberts, RC ;
Kelly, JJ ;
McCarthy, MM .
JOURNAL OF COMPARATIVE NEUROLOGY, 2001, 432 (02) :259-267
[44]   Estrogen facilitates induction of long term potentiation in the hippocampus of awake rats [J].
Montoya, DAC ;
Carrer, HF .
BRAIN RESEARCH, 1997, 778 (02) :430-438
[45]   Sexual differentiation of the vertebrate nervous system [J].
Morris, JA ;
Jordan, CL ;
Breedlove, SM .
NATURE NEUROSCIENCE, 2004, 7 (10) :1034-1039
[46]   REGIONAL SEX-DIFFERENCES IN SPINE DENSITY ALONG THE APICAL SHAFT OF VISUAL-CORTEX PYRAMIDS DURING POSTNATAL-DEVELOPMENT [J].
MUNOZCUETO, JA ;
GARCIASEGURA, LM ;
RUIZMARCOS, A .
BRAIN RESEARCH, 1991, 540 (1-2) :41-47
[47]  
MUNOZCUETO JA, 1990, BRAIN RES, V515, P64
[48]  
Murphy DD, 1996, J NEUROSCI, V16, P4059
[49]   SEXUAL DIMORPHISM IN SYNAPTIC ORGANIZATION IN THE AMYGDALA AND ITS DEPENDENCE ON NEONATAL HORMONE ENVIRONMENT [J].
NISHIZUKA, M ;
ARAI, Y .
BRAIN RESEARCH, 1981, 212 (01) :31-38
[50]   ORGANIZATIONAL ACTION OF ESTROGEN ON SYNAPTIC PATTERN IN THE AMYGDALA - IMPLICATIONS FOR SEXUAL-DIFFERENTIATION OF THE BRAIN [J].
NISHIZUKA, M ;
ARAI, Y .
BRAIN RESEARCH, 1981, 213 (02) :422-426