Abstract
Glutamate is involved in excitotoxic mechanisms by interacting with different receptors. Such interactions result in neuronal death associated with several neurodegenerative disorders of the central nervous system (CNS). The aim of this work was to study the time course of changes in the expression of GluR1 and GluR2 subunits of glutamate amino-acid-3-hydroxy-5-methyl-isoxazol-4-propionic acid (AMPA) receptors in rat hippocampus induced by NMDA intrahippocampal injection. Rats were submitted to stereotaxic surgery for NMDA or saline (control) microinjection into dorsal hippocampus and the parameters were evaluated 24 h, 1, 2, and 4 weeks after injection. The extension and efficacy of the NMDA-induced injury were evaluated by Morris water maze (MWM) behavioral test and Nissl staining. The expression of GluR1 and GluR2 receptors, glial fibrillary acidic protein (GFAP), and neuronal marker (NeuN) was analyzed by immunohistochemistry. It was observed the impairment of learning and memory functions, loss of neuronal cells, and glial proliferation in CA1 area of NMDA compared with control groups, confirming the injury efficacy. In addition, NMDA injection induced distinct changes in GluR1 and GluR2 expression over the time. In conclusion, such changes may be related to the complex mechanism triggered in response to NMDA injection resulting in a local injury and in the activation of neuronal plasticity.
Highlights
Glutamate is the main and most abundant excitatory neurotransmitter in the Central Nervous System (CNS) with key role in several physiological functions
The present study showed the time course of changes in the expression of GluR1 and GluR2 in hippocampus induced by a local injection of NMDA
Our results demonstrated that NMDA induced distinct alterations in the expression of each subunit depending on the specific hippocampus subfields and the time after injection
Summary
Glutamate is the main and most abundant excitatory neurotransmitter in the Central Nervous System (CNS) with key role in several physiological functions. The ionotropic glutamate receptors (iGluRs) are a complex of transmembrane proteins assemblies that reflect the receptor permeability to the influx of ions (Hollmann and Heinemann, 1994; Rosa, 2006). These receptors are classified according to their agonists N-methyl-D-aspartate (NMDA), amino-acid-3-hydroxy-5-methyl-isoxazol-4-propionic acid (AMPA), and kainate (KA). The alternative splicing of genes encoding the subunits originates two isoforms of each, flip and flop, with distinct physical and chemical properties The distribution of these subunits and isoforms is different considering the brain region and the stage of development (Sommer et al, 1990; Hollmann and Heinemann, 1994; Pires et al, 2000)
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