The proline-rich hypothalamic peptide is a modulator of functions of neurotrophins and neuronal activity in amyloid-induced neurodegeneration

On a model of neurodegeneration induced by neurotoxic peptide fragment (25–35) of β-amyloid (Aβ), we studied changes in the content of neurotrophins: insulin-like growth factor 1 (IGF-1) and nerve growth factor (NGF) in different brain areas, as well as the thymus, liver, and blood serum of rats under the influence of hypothalamic proline-rich peptide-1 (PRP-1). The effect of PRP-1 on the structural-functional state of the neurons was also studied. We showed that intramuscular injections of synthetic PRP-1 at a dose of 10 μg per 100 g of body weight for the first 9 days after intracerebroventricular administration of Aβ into the lateral brain ventricles of rats resulted in a considerable increase in the concentration of IGF-1 in all investigated brain structures, mainly, in the neocortex, hippocampus, and hypothalamus at 12 week of developing the neurodegeneration. This effect was maintained also after intramuscular administration of PRP-1 at 30 days after Aβ injection (a later date). However, as a result of PRP-1 action at early stages of the process, the tendency to decrease NGF content in the cortex, hippocampus and hypothalamus was observed. Electrophysiological and morphological studies of hippocampal neurons show, that by the 18th week after the beginning of neuro-degeneration, treatment with PRP-1 results in survival and further maintenance of cells, which indicates that PRP-1 has neuroprotective characteristics. We concluded that treatment with PRP-1 at Aβ-induced neuro-degeneration may provide normal functioning of neurons during a relatively long period of time by modulation the levels of neurotrophins both in brain and peripheria.