Neurosteroids in learning and memory processes.
ABSTRACT The discovery that neurosteroids could be synthesized de novo in the brain independent from the periphery and display neuronal actions led to great enthusiasm for the study of their physiological role. Pharmacological studies suggest that neurosteroids may be involved in several physiological processes, such as learning and memory. This chapter summarizes the effects of the administration of neurosteroids on learning and memory capabilities in rodents and in models of amnesia. We address the central mechanisms involved in mediating the modulation of learning and memory processes by neurosteroids. In this regard, the neurosteroid-modulated neurotransmitter systems, such as gamma-aminobutyric acid type A, N-methyl-D-aspartate, and cholinergic and sigma opioid systems, appear to be potential targets for the rapid memory alteration actions of neurosteroids. Moreover, given that some neurosteroids affect neuronal plasticity, this neuronal change could be involved in the long-term modulation of learning and memory processes. To understand the role of endogeneous neurosteroids in learning and memory processes, we present some physiological studies in rodents and humans. However, the latter do not successfully prove a role of endogenous neurosteroids in age-related memory impairments. Finally, we discuss the relative implication of a given neurosteroid vs its metabolites. For this question, a new approach using the quantitative determination of traces of neurosteroids by mass spectrometry seems to have potential for examining the role of each neurosteroid in discrete brain areas in learning and memory alterations, as observed during aging.
Article: Effect of 3α-anderostanediol and indomethacin on acquisition, consolidation and retrieval stage of spatial memory in adult male rats.[show abstract] [hide abstract]
ABSTRACT: Background: Testosterone and its metabolites have important roles in learning and memory. The current study has conducted to assess the effect of pre-training, post-training and pre-probe trial intrahippocampal CA1 administration of 3α-anderostanediol (one of the metabolites of testosterone) and indomethacin (as 3α-hydroxysteroid dehydrogenase enzyme blocker) on acquisition, consolidation and retrieval in Morris water maze (MWM) task. Methods: Adult male rats were bilaterally cannulated into CA1 region of hippocampus and then received 3α-diol (0.2, 1, 3 and 6 mug/0.5 mul/side), indomethacin (1.5, 3 and 6 mug/0.5 mul/side), indomethacin (3 mug/0.5 mul/side) + 3α-diol (1 mug/0.5 mul/side), 25-35 min before training, immediately after training and 25-35 min before probe trial in MWM task. Results: Our results showed that injection of 3α-diol and indomethacin significantly increased the escape latency and traveled distance to find hidden platform in acquisition and consolidation stage, but did not have any effect on retrieval of spatial learning as compared with the control group. Conclusion: It is concluded that intra-CA1 administration of 3α-diol and indomethacin could impair spatial learning and memory in acquisition and consolidation stage. Also, intrahippocampal injection of indomethacin + 3α-diol could not change spatial learning and memory impairment effect of indomethacin or 3α-diol in MWM task.Iranian biomedical journal 07/2012; 16(3):145-55.
Article: Low brain allopregnanolone levels mediate flattened circadian activity associated with memory impairments in aged rats.[show abstract] [hide abstract]
ABSTRACT: Sleep and cognitive impairments are two of the most prevalent neuropsychiatric disorders in the aged population. Age-related memory dysfunctions can result from alterations in sleep/wake circadian rhythm. However, the underlying mechanism of these alterations is unknown. Here, we demonstrate the role of alterations in brain steroid levels in age-related sleep-dependent memory impairment in rats. Sleep/wake circadian activity and spatial memory performance were evaluated in adult, middle-aged, and aged rats, and steroid levels were measured in brain structures involved in mediating sleep-dependent memory processes using gas chromatography/mass spectrometry. The causal relationship between circadian activity and allopregnanolone levels was assessed using an inhibitor of allopregnanolone synthesis (indomethacin). Similar to observations in humans, a subpopulation of middle-aged and aged rats show flattened amplitude of circadian activity associated with impaired spatial long-term memory performance. Sleep-dependent memory dysfunction was associated with a low level of allopregnanolone in the hypothalamus, pedunculopontine nucleus, and ventral striatum. Inhibition of allopregnanolone synthesis in young rats decreased allopregnanolone in the hypothalamus and produced flattened amplitude of circadian activity similar to aged rats. These findings identify brainstem and basal forebrain allopregnanolone as an essential endogenous substrate involved in mediating sleep-dependent memory function in young and aged rats. Allopregnanolone may play a critical role in preserving individuals from age-induced alterations in sleep and memory processes and may represent a novel target for attenuating age-related declines in sleep and memory.Biological psychiatry 11/2010; 68(10):956-63. · 8.93 Impact Factor