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.

A model synapse that incorporates the properties of short- and long-term synaptic plasticity.

We propose a general computer model of a synapse, which incorporates mechanisms responsible for the realization of both short- and long-term synaptic plasticity-the two forms of experimentally observed plasticity that seem to be very significant for the performance of neuronal networks. The model consists of a presynaptic part based on the earlier 'double barrier synapse' model, and a postsynaptic compartment which is connected to the presynaptic terminal via a feedback, the sign and magnitude of which depend on postsynaptic Ca(2+) concentration. The feedback increases or decreases the amount of neurotransmitter which is in a ready for release state. The model adequately reproduced the phenomena of short- and long-term plasticity observed experimentally in hippocampal slices for CA3-CA1 synapses. The proposed model may be used in the investigation of certain real synapses to estimate their physiological parameters, and in the construction of realistic neuronal networks.