title: Diabetes mellitus- and ageing-induced changes in the capacity for long-term depression and long-term potentiation inductions: toward a unified mechanism.
abstract: Long-lasting type 1 and type 2 diabetes mellitus (DM) are both associated with impaired cognitive function in humans. Animal models of DM have confirmed the detrimental effect of high blood glucose levels on learning and memory. What are the neural correlates of such impaired cognition? It is widely, although not universally, believed that long-lasting increase and decrease in synaptic strength, known as long-term potentiation (LTP) and depression (LTD), provide an important key to understanding the cellular and molecular mechanisms by which memories are formed and stored. The majority of animal studies that examined the effect of DM on LTD and LTP used the streptozotocin (STZ) rodent model of type 1 DM, with the exception of a few that used genetic models of type 2 DM. Studies in STZ-DM rodents show that cellular processes underlying synapse strengthening or weakening are not altered. Rather, the capacity for LTP induction is reduced whereas that for LTD induction is enhanced. The mechanisms underlying DM-related changes in LTD and LTP inductions are still unknown. However, that the levels of effective postsynaptic depolarization for LTD and LTP inductions are concomitantly shifted in opposite directions put constraints on them. Moreover, that DM-, metaplasticity-, stress- and ageing-related changes in LTD and LTP inductions exhibit the very same phenomenology suggests that they might involve common mechanisms. Dissecting out the mechanisms responsible for DM-related changes in the capacity for LTD and LTP inductions is helping to improve treatment of impaired cognitive function in DM patients.
authors.affiliation: Clermont Université, Université d'Auvergne, NEURO-DOL, BP 10448, F-63000 Clermont-Ferrand, France; Inserm, U1017, F-63000 Clermont-Ferrand, France. Electronic address: alain.artola@udamail.fr.
authors.forename: Alain
authors.initials: A
authors.lastname: Artola
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D003920:Diabetes Mellitus / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D006801:Humans; D017774:Long-Term Potentiation / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000502:physiology*
keywords: Ageing; Diabetes mellitus; Long-term depression; Long-term potentiation; Metaplasticity; Stress