Mayo W, Le Moal M, Abrous D N
INSERM U259, Institut François Magendie, Rue Camille Saint-Saens, 33077 Bordeaux Cedex, France.
Horm Behav. 2001 Sep;40(2):215-7. doi: 10.1006/hbeh.2001.1677.
Neurosteroids are a subclass of steroids that can be synthesized in the central nervous system independently of peripheral sources. Several neurosteroids influence cognitive functions. Indeed, in senescent animals we have previously demonstrated a significant correlation between the cerebral concentration of pregnenolone sulfate (PREG-S) and cognitive performance. Indeed, rats with memory impairments exhibited low PREG-S concentrations compared to animals with correct memory performance. Furthermore, these memory deficits can be reversed by intracerebral infusions of PREG-S. Neurotransmitter systems modulated by this neurosteroid were unknown until our recent report of an enhancement of acetylcholine (ACh) release in basolateral amygdala, cortex, and hippocampus induced by central administrations of PREG-S. Central ACh neurotransmission is involved in the regulation of memory processes and is affected in normal aging and in human neurodegenerative pathologies like Alzheimer's disease. ACh neurotransmission is also involved in the modulation of sleep-wakefulness cycle and relationships between paradoxical sleep and memory are well documented in the literature. PREG-S infused at the level of ACh cell bodies induces a dramatic increase of paradoxical sleep in young animals. Cognitive dysfunctions, particularly those observed in Alzheimer's disease, have also been related to alterations of cerebral plasticity. Among these mechanisms, neurogenesis has been recently studied. Preliminary data suggest that PREG-S central infusions dramatically increase neurogenesis. Taken together these data suggest that PREG-S can influence cognitive processes, particularly in senescent subjects, through a modulation of ACh neurotransmission associated with paradoxical sleep modifications; furthermore our recent data suggest a role for neurosteroids in the modulation of hippocampal neurogenesis.
神经甾体是一类甾体化合物，可在中枢神经系统中独立于外周来源合成。几种神经甾体影响认知功能。事实上，在衰老动物中，我们之前已经证明硫酸孕烯醇酮（PREG-S）的脑内浓度与认知表现之间存在显著相关性。确实，与记忆表现正常的动物相比，有记忆障碍的大鼠PREG-S浓度较低。此外，通过脑内注入PREG-S可逆转这些记忆缺陷。直到我们最近报道中枢给予PREG-S可增强基底外侧杏仁核、皮层和海马体中乙酰胆碱（ACh）的释放，这种神经甾体所调节的神经递质系统才为人所知。中枢ACh神经传递参与记忆过程的调节，在正常衰老以及人类神经退行性疾病如阿尔茨海默病中会受到影响。ACh神经传递还参与睡眠-觉醒周期的调节，文献中也充分记载了快速眼动睡眠与记忆之间的关系。在ACh细胞体水平注入PREG-S可使幼龄动物的快速眼动睡眠显著增加。认知功能障碍，尤其是在阿尔茨海默病中观察到的那些，也与脑可塑性的改变有关。在这些机制中，神经发生最近受到了研究。初步数据表明，脑内注入PREG-S可显著增加神经发生。综合这些数据表明，PREG-S可通过调节与快速眼动睡眠改变相关的ACh神经传递来影响认知过程，尤其是在衰老个体中；此外，我们最近的数据表明神经甾体在海马体神经发生调节中发挥作用。
