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Introduction: Alzheimer’s disease (AD) is a severe neurodegenerative disease characterized by loss of synaptic connection between neurons of the cortex and subcortical regions. The cholinergic deficit is a consistent and early finding in AD, hence acetylcholinesterase inhibitors (AChEIs) are used for symptomatic improvement of AD. Most of these therapeutic agents are hepatotoxic, leading to liver failure and other complications. Therefore, the study of new AChEIs with less toxic impact and better effectivity is a topical challenge. In view of this, we synthesized novel chemical compounds: TVA and TVS that possess AChEI activity and studied their neuroprotective effect in an experimental AD model. Materials and methods: Studies were performed on white rats. Acute toxicity studies were performed by Karber’s method. AD was induced via bilateral intracerebroventricular administration of Aβ 25–35. Histopathological examinations were performed in the hippocampus and the entorhinal cortex. Liver tissue was additionally examined to monitor the hepatotoxicity of these compounds. Results: Studies of the hippocampus showed that compared to control and TVA-treated groups, under the influence of TVS there were few morphological alterations. Experimental groups showed an increase in the glial cell count, compared to the intact animals. In comparison to the AD group, the increase in microglia was not that prominent under the action of the novel compounds. Under the influence of TVA and TVS, the entorhinal cortex was more susceptible to neuronal injury, although TVS protected pyramidal neurons. Also, the group treated with TVA had signs of acute liver damage, while under the influence of TVS there were no signs of liver changes. Discussion: Histopathological examination showed that the neurodegenerative processes in the hippocampus, as well as in the entorhinal cortex, were significantly reduced under the influence of TVS, compared with the control group. At the same time, TVA had no significant effect on the protection of neuronal cells. Also, TVS was less toxic, and there was no sign of hepatotoxicity during the experiments. Conclusion: These studies demonstrated that TVS possesses neuroprotective activity and reduces neuronal damage induced by Aβ. Graphical abstract:

Abstract We investigated the action of the new hypothalamic proline-rich peptide (PRP-1), normally produced by neurosecretory cells of hypothalamic nuclei (NPV and NSO), 3 and 4 weeks following rat sciatic nerve transection. The impulse activity flow of interneurons (IN) and motoneurons (MN) on stimulation of mixed (n. ischiadicus), flexor (n. gastrocnemius – G) and extensor (n. peroneus communis – P) nerves of both injured and symmetric intact sides of spinal cord (SC) was recorded in rats with daily administration of PRP-1 (for a period of 3 weeks) and without it (control). On the injured side of SC in control, there were no responses of IN and MN on ipsilateral G and P stimulation, while responses were elicited on contralateral nerve stimulation. The neuron responses on the intact side of SC were revealed in a reverse ratio. Thus, there were no effects upon stimulation of the injured nerve distal stump in the control because of the absence of fusion between transected nerve stumps. This was also testified by the atrophy of the distal stump and the absence of motor activity of the affected limb. In PRP-1-treated animals, the responses of SC IN and MN in postaxotomy 3 weeks on the injured side of SC at ipsilateral nerve stimulation and on the intact side at contralateral nerve stimulation were recorded because of the obvious fusion of the severed nerve stumps. The histochemical data confirmed the electrophysiological findings. Complete coalescence of transected fibers together with restoration of the motor activity of the affected limb provided evidence for reinnervation on the injured side. Thus, it may be concluded that PRP-1 promotes nerve regeneration and may be used clinically to improve the outcome of peripheral nerve primary repair. [ABSTRACT FROM AUTHOR]

Abstract The purpose of the present study was to evaluate the neuroprotective action of proline-rich peptide-1 (PRP-1) produced by hypothalamic nuclei cells (nuclei paraventricularis and supraopticus) following lateral hemisection of spinal cord (SC). The dynamics of rehabilitative shifts were investigated at various periods of postoperative survival (1–2, 3, and 4 weeks), both with administration of PRP-1 and without it (control). We registered evoked spike flow activity in both interneurons and motoneurons of the same segment of transected and symmetric intact sides of SC and below it on the stimulation of mixed (n. ischiadicus), flexor (n. gastrocnemius) and extensor (n. peroneus communis) nerves. In the control group (administration of 0.9% saline as placebo), no significant decrease of post-stimulus activity of neurons was observed on the transected side by the 2nd week. This activity strongly decreased by week 3 postaxotomy, with some increase on the intact side, possibly of compensatory origin. No shifts occurred by the 4th week. Regardless of the period of administration, PRP-1 increased neuronal activity on the transected side, with the same activation levels on both SC sides. These data were confirmed by histochemical investigation. PRP-1 administration, both daily and every other day, for a period of 2–3 weeks led to prevention of scar formation and promotion of the re-growth of white matter nerve fibers in the damaged area. It also resulted in prevention of neuroglial elements degeneration and reduction in gliosis expression in the lesion supporting neuronal survival. Thus, PRP-1 achieved protection against “tissue stress”, which was also confirmed by the registration of activity on the level of transection and restoration of the motor activity on the injured side. The obtained data propose the possibility of PRP-1 application in clinical practice for prevention of neurodegeneration of traumatic origin. [ABSTRACT FROM AUTHOR]