Differential Expression of AMPA Subunits Induced by NMDA Intrahippocampal Injection in Rats

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.

Secreted Amyloid Precursor Protein-Alpha Enhances LTP Through the Synthesis and Trafficking of Ca2+-Permeable AMPA Receptors

“…In response to synaptic activity ( Bagal et al, 2005 ; Kopec et al, 2006 ; Guire et al, 2008 ; Tanaka and Hirano, 2012 ; Park et al, 2016 ; Pandya et al, 2018 ), behavioral learning ( Whitlock et al, 2006 ; Fachim et al, 2016 ), and neuromodulators ( Leonoudakis et al, 2008 ; Jourdi and Kabbaj, 2013 ), cell surface or synaptic accumulation of GluA2-containing AMPARs has been shown to occur, typically following the incorporation of GluA1-containing homomers ( Shi et al, 1999 ; Bellone and Lüscher, 2005 , 2006 ; Guire et al, 2008 ; Hong et al, 2013 ; Park et al, 2016 ).…”

AMPA induced cognitive impairment in rats: Establishing the role of endoplasmic reticulum stress inhibitor, 4‐PBA

“…In the literature, it has been demonstrated that neurons of the CA1 region of the hippocampus are critically involved in learning and memory process of the animals (Huo et al, 2015). However, loss of the neurons in DG region was considered essential for the spatial orientation (Fachim et al, 2016).…”

“…CA1, CA2, CA3, and DG (Cortese & Phan, 2005;Fachim et al, 2016;Wiley et al, 2011;Yang et al, 2015). Following NMDA-induced excitotoxicity, a decline in the expression of the GLUR1 is suggested to be a major reason for the impaired long-term potentiation (LTP) and cognitive impairment (Fachim et al, 2016;Wiley et al, 2011;Yang et al, 2015).…”

Neuroprotective Effect of Optogenetics Varies With Distance From Channelrhodopsin-2 Expression in an Amyloid-β-Injected Mouse Model of Alzheimer’s Disease

“…Brain tissue was sectioned to 30 μm in the coronal plane at the target area and temporarily stored in a 12-well plate in PBS. Sections were treated with xylene and rehydrated in graded ethanol ( Fachim et al, 2016 ). Sections were blocked in 3% BSA at room temperature for 1 h and incubated in 0.3% Triton X-100/PBS with primary antibody overnight at 4°C.…”