Abstract

MANSILLA-OLIVARES, Armando. Signal transduction, pillar of the neurobiological integration of memory: An alternative view to the cholinergic hypothesis. Gac. Méd. Méx [online]. 2005, vol.141, n.6, pp.513-526. ISSN 2696-1288.

Neurophysiological, biochemical and molecular processes described in the integration of memory are closely related with neurotransmitters such as glutamate and serotonin (5HT) and with the function of calcium and potassium ion channels more than with cholinergic activity. In fact, glutamate and 5 HT receptors are closely related with Long-Term Potentiation (LTP) processes, the mechanism by which memory is preserved throughout time. That is, the activation of the 5 HT₄ receptor triggers a transduction signal that after influencing nuclear cell activity, provokes several presynaptic changes, which leads to the displacement of magnesium from the postsynaptic area depolarizing the neuron and leading to the activation of N methyl -D-aspartate receptors (NMDA). As a whole, this process contributes to the support and perpetuation of LTP, which consists of the following processes: LTP1 that depends on protein kinase activity; LTP2 linked to translation of genes; and LTP3 closely related to genes transcription. On the opposite side but in perfect balance, we find the mechanism of Long Term depression (LTD), which is triggered instead when the Ca++ flow decreases in the presynaptic neuron activating the inhibitor 1 enzyme that promotes the dephosphorylation of a calmodulin dependent protein kinase II and as a result, the inhibition of autophosphorylation and consequently of LTP too. Despite the widespread dissemination of the cholinergic hypothesis in Alzheimer's disease, memory build up rather than involving acetylcholine essentially depends on the participation of other neurotransmitters such as 5 HT and glutamate, which have not been adequately considered in the treatment of this disease. However, beyond neurotransmission, it is the cellular mechanism of autophosphorylation of several protein kinases, the process susceptible of being activated or controlled by the action of distinct substances. In such a case, it would be possible to exert some influence on gene expression improving perhaps, some of the physiopathological deficits that characterize memory disruption.

Keywords : Cognitive physiopathology; signal transduction; long-term-potentiation; long-term-depression; autophosphorylation; memory physiology and physiopathology.

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