Neuroprotection by hypothalamic peptide proline-rich peptide-1 in Abeta25-35 model of Alzheimer's disease.
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 Abeta25-35. The diseased rats received systemic administration of PRP-1 or placebo control.


RESULTS
Abeta25-35 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 Abeta25-35 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. Abeta25-35 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 Abeta25-35. This suggests that PRP-1 could be a potential therapeutic agent for specific neurodegenerative diseases.
Galoyan
Armen A
AA
Buniatyan Institute of Biochemistry, National Academy of Sciences of the Republic of Armenia, Yerevan, Armenia.
Sarkissian
John S
JS
Chavushyan
Vergineh A
VA
Meliksetyan
Irina B
IB
Avagyan
Zaruhi E
ZE
Poghosyan
Mikhail V
MV
Vahradyan
Hasmik G
HG
Mkrtchian
Hovhannes H
HH
Abrahamyan
Davit O
DO
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D004195:Disease Models, Animal; D004594:Electrophysiology; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D007031:Hypothalamus / Q000378:metabolism; D007276:Injections, Intraventricular; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D055232:Proline-Rich Protein Domains; D051381:Rats; D017208:Rats, Wistar
D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents