Neurobiology of learning and memory
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Neurobiol Learn Mem · Sep 2011
Gami-Chunghyuldan ameliorates memory impairment and neurodegeneration induced by intrahippocampal Aβ 1-42 oligomer injection.
Soluble oligomeric forms of amyloid beta (AβO) are regarded as a main cause of synaptic and cognitive dysfunction in Alzheimer's disease (AD) and have been a primary target in the development of drug treatments for AD. The present study utilized a mouse model of AD induced by intrahippocampal injection of AβO (10 μM) to investigate the effects of Gami-Chunghyuldan (GCD), a standardized multi-herbal medicinal formula, on the presentation of memory deficits and neurohistological pathogenesis. ⋯ In addition, GCD prevented AβO-triggered synaptic disruption and cholinergic fiber loss. These results suggest that GCD may be useful in the prevention and treatment of AD.
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Neurobiol Learn Mem · Sep 2011
Activation of cannabinoid CB1 receptors in the central amygdala impairs inhibitory avoidance memory consolidation via NMDA receptors.
In the present study, we investigated the influence of bilateral intra-central amygdala (intra-CeA) microinjections of N-methyl-D-aspartate (NMDA) receptor agents on amnesia induced by a cannabinoid CB1 receptor agonist, arachydonilcyclopropylamide (ACPA). This study used a step-through inhibitory (passive) avoidance task to assess memory in adult male Wistar rats. The results showed that intra-CeA administration of ACPA (2 ng/rat) immediately after training decreased inhibitory avoidance (IA) memory consolidation as evidenced by a decrease in step-through latency on the test day, which was suggestive of drug-induced amnesia. ⋯ Although post-training intra-CeA administration of the NMDA receptor antagonist, D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5; 0.01, 0.05 and 0.1 μg/rat) alone had no effect, its co-administration with an ineffective dose of ACPA (1 ng/rat) impaired IA memory consolidation. Post-training intra-CeA microinjection of an ineffective dose of D-AP5 (0.01 μg/rat) prevented an NMDA response to the impaired effect of ACPA. These results suggest that amnesia induced by intra-CeA administration of ACPA is at least partly mediated through an NMDA receptor mechanism in the Ce-A.
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A new line of neuroscience research suggests that epigenetics may be the site of nature and nurture integration by providing the environment with a mechanism to directly influence the read-out of our genome. Epigenetic mechanisms in the brain are a series of post-translational chromatin and DNA modifications driven by external input. Given the critical hub that epigenetics appears to be, neuroscientists have come to suspect its fundamental influence on how our minds change in response to our unique environment and, in turn, how these changes can then impact our future interactions with the environment. ⋯ With the majority of us working with an eye toward therapeutics, the question naturally arises: "Has neuroepigenetics gotten us closer to treating memory disorders and if so, where do we go from here?" This review will begin with a brief exploration of recent advances in our understanding of how epigenetic mechanisms contribute to learning and memory processes that are susceptible to failure. Next the implications for disorders of cognition, such as Alzheimer's disease, will be discussed. Finally, we will use parallels from the field of cancer to speculate on where we should consider heading from here in the pursuit of therapeutics.
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Neurobiol Learn Mem · Jul 2011
ReviewEpigenetics in the mature mammalian brain: effects on behavior and synaptic transmission.
The role of epigenetic mechanisms in control of gene expression during mammalian development is well established. Associations between specific DNA or histone modifications and numerous neurodevelopmental and neurodegenerative disorders implies significant consequences of epigenetic dysregulation in both the developing and mature brain, the latter of which is the general focus of this review. Accumulating evidence suggests that epigenetic changes are involved in normal cognitive processes in addition to neurological and psychiatric disorders. ⋯ DNA methylation and histone acetylation have also been implicated in the modulation of basal synaptic transmission and the balance between excitation and inhibition in various brain regions. Studies have begun to uncover some of the alterations in gene expression that appear to mediate many of these effects, but an understanding of the precise mechanisms involved is still lacking. Nevertheless, the fundamental importance of epigenetic processes in influencing neuronal activity is becoming increasingly evident.
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Neurobiol Learn Mem · Jul 2011
ReviewThe role of histone acetylation in age-associated memory impairment and Alzheimer's disease.
Learning and memory are cognitive processes that are tightly regulated. A proper genome-environment interaction is a pre-requisite for cognitive function. ⋯ With a specific focus on histone acetylation, we will discuss recent research in the field of epigenetic mechanisms of learning and memory. We will also specifically address the role of histone acetylation in age-associated memory impairment and Alzheimer's disease and ask the question why targeting the epigenome could be a suitable strategy for neuroprotection and neuroregeneration.