Neural plasticity and the brain renin-angiotensin system.

The brain renin-angiotensin system mediates several classic physiologies including body water balance, maintenance of blood pressure, cyclicity of reproductive hormones and sexual behaviors, and regulation of pituitary gland hormones. In addition, angiotensin peptides have been implicated in neural plasticity and memory. The present review initially describes the extracellular matrix (ECM) and the roles of cell adhesion molecules (CAMs), matrix metalloproteinases, and tissue inhibitors of metalloproteinases in the maintenance and degradation of the ECM. It is the ECM that appears to permit synaptic remodeling and thus is critical to the plasticity that is presumed to underlie mechanisms of memory consolidation and retrieval. The interrelationship among long-term potentiation (LTP), CAMs, and synaptic strengthening is described, followed by the influence of angiotensins on LTP. There is strong support for an inhibitory influence by angiotensin II (AngII) and a facilitory role by angiotensin IV (AngIV), on LTP. Next, the influences of AngII and IV on associative and spatial memories are summarized. Finally, the impact of sleep deprivation on matrix metalloproteinases and memory function is described. Recent findings indicate that sleep deprivation-induced memory impairment is accompanied by a lack of appropriate changes in matrix metalloproteinases within the hippocampus and neocortex as compared with non-sleep deprived animals. These findings generally support an important contribution by angiotensin peptides to neural plasticity and memory consolidation.

Ethanol-induced impairment of spatial memory and brain matrix metalloproteinases.

The formation of spatial memory appears to be dependent upon an intact hippocampus capable of the specific biochemical changes associated with synaptic remodeling. Hippocampal damage results in the disruption of synaptic remodeling and the acquisition of spatial memory tasks. Ethanol also disrupts normal hippocampal functioning and spatial memory. The present investigation established a dose-response relationship between ethanol treatment and impairment of spatial memory as measured using the circular water maze task. Intraperitoneal ethanol doses of 1.5 and 2 g/kg significantly increased the latency and distance swam to find the submerged pedestal as compared with a 1 g/kg dose, and 0.15 M NaCl vehicle control treatments. On days 2, 4, and 6 of acquisition animals were sacrificed and brain tissues were retained from the hippocampus, prefrontal neocortex, and cerebellum for measurement of matrix metalloproteinases (MMPs). The results indicated that ethanol treatment interfered with MMP-9, but not MMP-2, activity in the hippocampus, and to a lesser degree in the prefrontal cortex. No changes in the cerebellum were measured. Elevations in MMP activity appear to be a prerequisite to reconfiguration of extracellular matrix cell adhesion molecules thought to be important in the process of synaptic plasticity, which in turn appears to be necessary for memory consolidation. Thus, ethanol-induced impairment in the acquisition of spatial memory tasks may, in part, be due to disruption of brain MMP activity.