El sistema GABAérgico en el deterioro cognitivo y la depresiónEstudios en la enfermedad de Alzheimer y modelos animales

Résumé

Titulo: EL SISTEMA GABAERGICO EN EL DETERIORO COGNITIVO Y LA DEPRESIÓN. ESTUDIOS EN LA ENFERMEDAD DE ALZHEIMER Y MODELOS ANIMALES RESUMEN: Alzheimer's disease (ad) is a chronic progressive disorder characterised by dementia but often featuring behavioural and psychological syndromes. The involvement of the GABAergic system in cognitive and non-cognitive symptoms in AD was studied. in addition to cholinergic deficits, significant decreases in GABA content were found in frontal and temporal cortex. ChAT/GABA ratio correlated significantly to cognitive status, expressed as mmse score. Both GABA levies and GABAA/BZ receptor densities showed significant correlations with depression in AD. Cognitive deficits in AD have been closely related to eholinergic déficits. We have compared different markers of eholinergic function in two situations of hipoactiviy: AD patients and animáis with a eholinergic lesión. Based on correlations found to ChAT activity, basal ACh release and cognitive déficit of AD, AChE activity was suggested to be an effective marker to evaluate eholinergic deficits and associated cognitive impairments. in an animal model that resemble the eholinergic deafferentation observed in frontal cortex of AD, we found that a combined blockade of GABAergic and serotonergic systems siqnificantly increased "in vivo" and "in vitro" ACh release. The chronic mild stress, an animal model of depression, no alterations in the GABA content and the GABAA receptor expression were found. However, gabaa receptors showed a relation to behavioural (anhedonia) and biochemical (corticosterone levéis) markers of depresión. In conclusion, it is suggested that the pharmacological modulation of GABAergic system could be a therapeutical approach in the treatment of mental diseases, such as cognitive disorders and depression