Early experience, stressful dysregulation of the hormonal axis and age-related vulnerability to neurodegenerative processus: a longitudinal study in the rat.

The deleterious effects of particular environmental situations have been su spected to augment the repercussions of cerebral injuries leading to increa sed vulnerability during ageing. The relationship between the hormones of t he hypothalamo-pituitary-adrenal axis, mainly glucocorticosteroids, and cer ebral structures like the hippocampus has been the subject of intense inves tigation in the recent years. Data suggest that long-term elevated blood le vels of these hormones can induce neuronal alterations leading to cognitive dysfunction. This hypothesis has been tested with relevant animal models o f normal/abnormal ageing. The models are based on the existence of consider able inter-individual differences in the degree of age-related cognitive im pairments observed in rodents. Results show that long-term glucocorticoster oid exposure induces cerebral changes related to the action of these hormon es on their central receptors. Experimental data are in accordance with cli nical investigations suggesting that hormonal changes, and chronic me event s, could be considered as a predictive factor of future cognitive dysfuncti on.