Animal models in Alzheimer's disease research: Their value for understanding the AD etiopathogeny and for establishing AD therapies | MODELOS ANIMALES PARA EL ESTUDIO DE LA ENFERMEDAD DE ALZHEIMER: APORTACIONES AL CONOCIMIENTO DE LA ETIOPATOGENIA Y LA TERAPEUTICA

Abstract

Alzheimer Disease (AD) is a very important medical, social and economical problem in developed countries. Current data on the spanish situation is not available, but we can consider that in a few years, more than 500.000 people will suffer this neurodegenerative process in our community. Around the world an increasing interest in basic and clinical research on this particular dementia has been produced. Although any animal can suffer spontaneously AD and any agent can induce this disorder, distinct experimental AD-models have been outlined for studying, in laboratories, selected ethipathogenic and therapeutic aspects on AD. The following models can be mentioned as the most important: i) normal senile animals; ii) animals with cerebral beta fibrillosis; and iii) animals with selective lesions in cortical regulatory neuronal systems. The most useful models would be the last ones, supported by the ethiopathogenic theories which are proposed to explain AD, mainly the 'cholinergic theory'. Stereotactic injections of neurotoxins (ibotenic, quisqualic and related acids) in the cholinergic centers of the basal forebrain (the septum, the diagonal band of Broca and the nucleus basalis magnocellularis, the rodent equivalent of the Meynert nucleus in man) that innervate specific parts of brain cortex have been useful in the study of the changes promoted by anatomical or functional deinnervation. High cortical cholinergic deficits in cholinergic enzymes and choline transport, small receptor deficits and impairment in learning and memory abilities are provoked in the long-term follow-up of these lesioned animals. In the AD-models several therapeutic approaches have been teste. The most promising could be: substitutive cholinomimetic approaches (drug or neuronal implants); NGF and nerve growth factor-like therapeutics; and nootropic treatments. Pyritinol, a nootropic with clinical success in the first phases of AD, has been tested in models obtained alter quisqualic nbm-lesioning. In a model in which a number of surviving neurons can be detected after lesioning, the drug promotes a quick recovery of the depressed cortical cholinergic parameters. This effect has not been observed in a strongly nbm-lesioned model. The necessity of an early diagnosis of AD is strongly stressed to obtain the highest benefit from the plastic-hyperactive abilities of the cholinergic neurons before they reach a non-responsive state in their neurodegenerative pathway.Peer Reviewe