CHANGES IN NMDA RECEPTOR SUBUNITS EXPRESSION AFTER SPATIAL LEARNING IN A TRANSGENIC RAT MODEL OF ALZHEIMER DISEASE

ALEJANDRA AGUIRRE; MAGALÍ CECILIA CERCATO; EDGAR KORNISIUK; CECILIA VÁZQUEZ; MARÍA VERÓNICA BÁEZ; NATALIA COLETTIS; CLAUDIO CUELLO; DIANA JERUSALINSKY

Rio de Janeiro

Congreso; IBRO - 9th World Congress International Brain Research Organization; 2015

International Brain Research Organization

NMDA receptor (NMDAR) plays a critical role in physiological synaptic plasticity and has been involved in neurodegenerative disorders like Alzheimer disease (AD). NMDAR are heterotetramers composed by 2 GluN1 obligatory subunits and 2 regulatory subunits. In the central nervous system (CNS) regions involved in cognitive functions, GluN2A and GluN2B subunits are the major regulatory subunits. We have shown that about one hour following memory acquisition in the rat, in a hippocampus depending task like open field (OF) habituation; or after the effective induction of LTP in rat hippocampal fresh slices, both GluN1 and GluN2A subunits expression transiently increase in the hippocampus. We proposed that this modification in subunits levels could play a role in keeping an already established plasticity and protecting synapses from further plasticity to occur. Taking into account that memory acquisition is deeply affected in AD patients; we decided to investigate the pattern of NMDAR subunits expression in a transgenic model of Alzheimer disease, the McGilll-APP1 transgenics rats (Leon et al, 2010), carrying the human APP with the familiar AD mutations Swedish and Indiana. In this model, Ab levels are increased at 3 months and amyloid plates were observed at 12 months in homozygous animals. Tg rats and wild tipe (WT) rats of etiher 3-4 months or 12-13 months, were exposed to a 5 minutes session (training, tr) in an OF, which led to habituation to the environment. Other groups of rats were exposed again to the same OF to evaluate long term memory (LTM) 24 hours after tr (test, te). Both, WT and Tg rats seemed to learn in a similar way, expressing working memory as well as LTM. After behavioral task, rats were euthanized and hippocampal NMDAR subunits level was analyzed by westernblot. While NMDAR subunits transient increase was rather similar in young rats either WT or Tg, there were no changes after learning in one year old rats. In those Tg animals, GluN2A subunit appeared currently increased compared with its level in WT rats. We hypothesized that this ?constitutive? higher level of GluN2A could be related to synapse/neuron protection against pathological plasticity eventually caused by the attack by Aβ-oligomers