• Osman Sinen, Ayşegül Gemici Sinen, and Narin Derin.
• Department of Physiology, Turkey. Electronic address: osmansinen@akdeniz.edu.tr.
• Neuroscience. 2024 Nov 13.

AbstractNeuropeptide-S (NPS) has been demonstrated to mitigate learning and memory deficits in experimental models of Parkinson's Disease (PD). Despite this, the precise mechanisms through which NPS exerts its influence on cognitive functions remain to be fully unknown. This study aims to elucidate the effects of central administration of NPS on learning and memory deficits associated with an experimental rat hemiparkinsonian model, examining both electrophysiological and molecular parameters. The hemiparkinsonian model was established via stereotactic injection of 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle. Central NPS (1 nmol, icv) was administered into the lateral ventricle via a cannula for seven consecutive days following the 6-OHDA lesion. The Morris water maze and object recognition tests were used to evaluate the rat's learning and memory abilities. Long-term potentiation (LTP) recordings were conducted to assess hippocampal synaptic plasticity. Immunohistochemistry was employed to determine the expression levels of phosphorylated CaMKII (pCaMKII), GluR1, and GluR2 in the hippocampus. The 6-OHDA-induced decline in cognitive performance was significantly (p < 0.05) improved in rats that received central NPS. In 6-OHDA-lesioned rats, NPS treatment significantly (p < 0.05) enhanced the amplitude of LTP at the dentate gyrus/perforant path synapses. Furthermore, NPS significantly (p < 0.05) increased the number of pCaMKII and GluR1 immunoreactive cells in the hippocampus, which had been diminished due to 6-OHDA, except for GluR2 levels. These findings provide insight into the mechanisms by which central NPS administration enhances cognitive functions in an experimental model of PD, highlighting its potential therapeutic benefits for addressing cognitive deficits in PD.Copyright © 2024. Published by Elsevier Inc.

4 keywords...

hide…