Neuroprotection by hypothalamic peptide proline-rich peptide-1 in Aβ25–35 model of Alzheimer's disease

Abstract 

Background

This work sought to determine the effects of hypothalamic proline-rich peptide (PRP)-1 in a rat model of Alzheimer's disease.

Methods

Complex histochemical, electrophysiologic, and behavioral analyses were performed on intact or diseased Wistar rats (n = 28). Pathologic conditions were induced by bilateral intracerebroventricular injection of amyloid peptide Aβ25–35. The diseased rats received systemic administration of PRP-1 or placebo control.

Results

Aβ25–35 caused cellular neurodegeneration with marked glial reaction in the hippocampal complex and almost full destruction of the dentate fascia, which was not observed in conditions of PRP-1 administration after Aβ25–35 injection. Hippocampal neurons of intact animals responded to high-frequency (tetanic) stimulation of entorhinal cortex of ipsilateral cerebral hemisphere by tetanic and posttetanic potentiation of a different intensity and duration, which was accompanied by posttetanic depression. Aβ25–35 led to significant changes in the level and pattern of hippocampal neuronal activity, indicating the absence of both tetanic and posttetanic activity. Poststimulus activity manifestations rarely occurred and rapidly decreased after repeated trials. This indicated the focal character of lesion. Regular administration of PRP-1 for 4 weeks resulted in optimal restoration of electrophysiologic parameters. PRP-1 maintained the initial learning level achieved in a behavioral study in a Morris water maze.

Conclusions

Systemic administration of PRP-1 possesses neuroprotective effects and can prevent the neurodegeneration in hippocampus induced by Aβ25–35. This suggests that PRP-1 could be a potential therapeutic agent for specific neurodegenerative diseases.

Keywords: Hippocampus, Entorhinal cortex, Amyloid peptide Aβ25-35, Hypothalamic proline-rich peptide PRP-1, Histochemical study, Tetanic and posttetanic potentiation and depression, Learning in water maze