Tesis doctoral de Bárbara Aisa Vega
Exposure to early stressful adverse life events may increase vulnerability to psychopathology in adult life. There are important memory disturbances in stress-related psychiatric disorders. Male and females wistar rats that experienced 3-hour daily separations from the dam during the first 3 weeks of life (maternal separation, ms) showed in adulthood a depressive-like behaviour and increased hypothalamic¿pituitary¿adrenal (hpa) axis responsiveness to stressors. Ms produced significant learning impairments both in the morris water maze and in the novel object recognition test (nort). The glucocorticoid receptor antagonist mifepristone and the í¢-adrenoceptor antagonist propranolol were able to completely reverse the depressive-like behaviour and the memory deficits observed in ms rats. Our data support the hypothesis that elevated secretion of glucocorticoids may be associated to behavioural and cognitive deficits in ms rats. The stress hyperresponsiveness observed in ms rats could be attributed, at least in part, to an impaired feedback sensitivity mediated by hippocampal glucocorticoid receptors. It can also be suggested the possible involvement of the noradrenergic system in cognitive impairments mediated by glucocorticoids in the ms model. These present findings are discussed in terms of gender differences in adulthood. Moreover, adverse experiences early in life, may sensitize specific neurocircuits to subsequent stressors, thereby increasing vulnerability to the onset of psychopathology. We have evaluated in maternal separation (ms) rats, the effects of a selective cholinergic lesion. Ms rats subjected to a cholinergic lesion, showed significant decreases in both chat and ache activity compared to control lesioned rats. Morris water maze results revealed a significant impairment in learning and memory function in ms adult rats and further cognitive deficits after the selective cholinergic lesion. The selective lesion of cholinergic neurons induced a significant decrease in glucocorticoid receptor density in ms rats, accompanied by increases in crf mrna expression. Decreases in ngf and increases in ngf-p75 receptor expression have also been found in ms rats. Our results suggest that vulnerability of basal forebrain cholinergic nerve cells is strongly affected by an increased activity of the hpa axis associated to ms. The present data are discussed not only in terms of conditions that occur during ageing or alzheimer disease, but also regarding a purported involvement of the cholinergic system in the regulation of hpa axis activity. This study investigated the effects of ms on the expression of neural plasticity markers and a purported relationship to cognitive processes. Spatial learning significant increased the expression of total levels of the neural cell adhesion molecule (ncam), as well as its three major isoforms, both in the control and ms groups. Interestingly, these increases in ncam expression after learning were lower in ms animals, compared with control rats. Ms induced a significant decrease in total levels of ncam, and specifically, in the ncam-140 isoform expression. In the hippocampus of ms rats there was a significant decrease in bdnf and synaptophysin densities. Cell proliferation, was also decreased in ms rats. Altogether these results suggest that ms can alter normal brain development, providing a potential mechanism by which early environmental stressors may influence vulnerability to show cognitive impairments later in life.
Datos académicos de la tesis doctoral «La separación materna, un modelo experimental de depresión basado en una respuesta alterada al estrés«
- Título de la tesis: La separación materna, un modelo experimental de depresión basado en una respuesta alterada al estrés
- Autor: Bárbara Aisa Vega
- Universidad: Navarra
- Fecha de lectura de la tesis: 23/06/2008
Dirección y tribunal
- Director de la tesis
- María Javier Ramirez Gil
- Tribunal
- Presidente del tribunal: José javier Meana Martinez
- césar Venero nuñez (vocal)
- mara Dierssen sotos (vocal)
- rosa María Tordera baviera (vocal)