Affiliation:
1. Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
2. Croatian Institute for Brain Research, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Abstract
Cognitive deficit is a frequent non-motor symptom in Parkinson’s disease (PD) with an unclear pathogenesis. Recent research indicates possible involvement of insulin resistance and glutamate excitotoxicity in PD development. We investigated cognitive performance and the brain glutamate and insulin signaling in a rat model of PD induced by bilateral intrastriatal injection of 6-hydroxydopamine (6-OHDA). Cognitive functions were assessed with Passive Avoidance (PA) and Morris Water Maze (MWM) tests. The expression of tyrosine hydroxylase (TH) and proteins involved in insulin (insulin receptor - IR, phosphoinositide 3 kinase - pI3K, extracellular signal-regulated kinases-ERK) and glutamate receptor (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptos-AMPAR, N-methyl-D-aspartate receptor - NMDAR) signaling was assessed in the hippocampus (HPC), hypothalamus (HPT) and striatum (S) by immunofluorescence, Western blot and enzyme-linked immunosorbent assay (ELISA). Three months after 6-OHDA treatment, cognitive deficit was accompanied by decreased AMPAR activity and TH levels (HPC, S), while levels of the proteins involved in insulin signaling remained largely unchanged. Spearman’s rank correlation revealed a strong positive correlation for pAMPAR-PA (S), pNMDAR-pI3K (HPC) and pNMDAR-IR (all regions). Additionally, a positive correlation was found for TH-ERK and TH-pI3K, and a negative one for TH-MWM/errors and pI3K-MWM/time (S). These results suggest a possible association between brain glutamate (but not insulin) signaling dysfunction and cognitive deficit in a rat PD model, detected three months after 6-OHDA treatment.
Funder
Croatian Science Foundation
University of Zagreb
Scientific Centre of Excellence for Basic, Clinical and Translational Neuroscience
European Regional Development Fund
Subject
General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)
Cited by
5 articles.
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