RESUMO
The effects of intra-hippocampal manipulation of glycine receptors on the reconsolidation of recent and late long-term spatial memory were evaluated and assessed in the Morris water maze. The results obtained from the intra-hippocampal infusion of glycine and taurine demonstrated that taurine at a 100 nmol/side dose impaired the reconsolidation of recent and late long-term spatial memory. In comparison, at a dose of 10 nmol/side, it only affected the reconsolidation of late long-term spatial memory, reinforcing that there are differences between molecular mechanisms underlying recent and late long-term memory reconsolidation. On the other hand, glycine impaired the reconsolidation of early and late spatial memory when infused at a dose of 10 nmol/side, but not at a dose of 100 nmol/side, unless it is co-infused with an allosteric site antagonist of the NMDA receptor. Altogether these results show that glycine acting in situ in the hippocampal CA1 region exerts a pharmacological effect on U-curve, which can be explained by its concomitant action on its ionotropic receptor GlyR and on its NMDA receptor co-agonist site.
Assuntos
Glicina , Memória de Longo Prazo , Ratos Wistar , Receptores de Glicina , Memória Espacial , Taurina , Animais , Receptores de Glicina/metabolismo , Receptores de Glicina/efeitos dos fármacos , Masculino , Glicina/farmacologia , Ratos , Memória Espacial/efeitos dos fármacos , Memória Espacial/fisiologia , Memória de Longo Prazo/efeitos dos fármacos , Memória de Longo Prazo/fisiologia , Taurina/farmacologia , Taurina/administração & dosagem , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Consolidação da Memória/efeitos dos fármacos , Consolidação da Memória/fisiologia , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/metabolismo , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Região CA1 Hipocampal/efeitos dos fármacos , Região CA1 Hipocampal/metabolismo , Região CA1 Hipocampal/fisiologia , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologiaRESUMO
Alzheimer's disease is a neurodegenerative condition that causes changes in memory and cognition, in addition to behavioral disorders, and most commonly affects the elderly. Several studies in the literature have presented therapeutic measures in an attempt to interfere with the pathogenic mechanisms of the disease and to mitigate its clinical manifestations. Some factors, such as excitotoxicity, cholinergic dysfunctions, oxidative stress, tau protein hyperphosphorylation, changes in amyloid-beta peptide metabolism, herpes viruses, apolipoprotein E, glycogen synthase kinase 3, insulin resistance, and the endocannabinoid system seem to be related to pathophysiology of Alzheimer's disease. Given this, a literature review was carried out to address the molecular mechanisms associated with the pathophysiological hypotheses previously mentioned, aiming to better understanding their underlying causes and contributing to possible pharmacological strategies about treatment of the disease.
Assuntos
Doença de Alzheimer , Resistência à Insulina , Idoso , Humanos , Cognição , Estresse OxidativoRESUMO
Abstract Alzheimer's disease is a neurodegenerative condition that causes changes in memory and cognition, in addition to behavioral disorders, and most commonly affects the elderly. Several studies in the literature have presented therapeutic measures in an attempt to interfere with the pathogenic mechanisms of the disease and to mitigate its clinical manifestations. Some factors, such as excitotoxicity, cholinergic dysfunctions, oxidative stress, tau protein hyperphosphorylation, changes in amyloid-beta peptide metabolism, herpes viruses, apolipoprotein E, glycogen synthase kinase 3, insulin resistance, and the endocannabinoid system seem to be related to pathophysiology of Alzheimer's disease. Given this, a literature review was carried out to address the molecular mechanisms associated with the pathophysiological hypotheses previously mentioned, aiming to better understanding their underlying causes and contributing to possible pharmacological strategies about treatment of the disease.