Association of Cognitive Deficit with Glutamate and Insulin Signaling in a Rat Model of Parkinson’s Disease

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.

Altered Secretion, Constitution, and Functional Properties of the Gastrointestinal Mucus in a Rat Model of Sporadic Alzheimer’s Disease

“…16 Successful induction of the model was confirmed by performing standardized tests used for the assessment of aversive and spatial memory following previously described protocols (Supporting Information). 60 The animals were anesthetized (70 mg/ kg ketamine; 7 mg/kg xylazine) and subjected to transcardial perfusion with saline followed by 4% paraformaldehyde (pH 7.4). Duodenal tissue (post-gastric 2 cm) was fixed in 4% paraformaldehyde, dehydrated, and embedded in paraffin blocks.…”

Experimental parkinsonism induced by tetanus toxin injected into basal ganglia

“…Caudate putamen was cut out manually by using the scalpel tip from thick coronal sections with the help of stereotaxic rat atlas (Paxinos and Watson, 2005) [13] as previously described [26], weighed and stored at -80 °C. Measurement of protein concentration, electrophoresis, protein visualization and transfer were done as previously described [27]. In brief, protein isolation was performed by tissue sonication inside the modified RIPA-based buffered lysis buffer, and the protein content was assessed by Lowry method.…”

“…The membrane and gel protein bands were analyzed by Fiji version of ImageJ software (U.S. National Institutes of Health, Bethesda, MD, USA). The protein intensities were expressed proportionally to the signal of total proteins in the corresponding sample on the gel or membrane [27].…”

My friend MIROSLAV: A Hackable Open-Source Hardware and Software Platform for High-Throughput Rodent Activity Monitoring in the Home Cage

“…The control group (CTR, n = 15) was given 0.05 M citrate buffer (pH 4.5) intracerebroventricularly, and for the streptozotocin-treated group (STZ, n = 15), STZ (1.5 mg/kg) was freshly dissolved in the citrate buffer. Citrate buffer or STZ solution (2 μL) was given into each ventricle twice across 48 hours, at coordinates −1.5 mm posterior, ±1.5 mm lateral, and +4 mm ventral to the bregma [32,37–39]. For the procedure, the animals were anaesthetised with an intraperitoneal injection of ketamine/xylazine (70/7 mg/kg).…”

“…The rat model of sporadic Alzheimer's disease the bregma [32,[37][38][39]. For the procedure, the animals were anaesthetised with an intraperitoneal injection of ketamine/xylazine (70/7 mg/kg).…”