Studying the Specific Activity of the Amide Form of HLDF-6 Peptide using the Transgenic Model of Alzheimer’s Disease

Abstract

The neuroprotective and nootropic activities of the amide form (AF) of the HLDF-6 peptide (TGENHR-NH2) were studied in transgenic mice of the B6C3-Tg(APPswe,PSEN1de9)85Dbo (Tg+) line (the animal model of familial Alzheimer’s disease (AD)). The study was performed in 4 mouse groups: group 1 (study group): Tg+ mice intranasally injected with the peptide at a dose of 250 μg/kg; group 2 (active control): Tg+ mice intranasally injected with normal saline; group 3 (control 1): Tg- mice; and group 4 (control 2): C57Bl/6 mice. The cognitive functions were evaluated using three tests: the novel object recognition test, the conditioned passive avoidance task, and the Morris water maze. The results testify to the fact that the pharmaceutical substance (PhS) based on the AF of HLDF-6 peptide at a dose of 250 μg/kg administered intranasally efficiently restores the disturbed cognitive functions in transgenic mice. These results are fully consistent with the data obtained in animal models of Alzheimer’s disease induced by the injection of the beta-amyloid (βA) fragment 25-35 into the giant-cell nucleus basalis of Meynert or by co-injection of the βA fragment 25-35 and ibotenic acid into the hippocampus, and the model of ischemia stroke (chronic bilateral occlusion of carotids, 2VO). According to the overall results, PhS based on AF HLDF-6 was chosen as an object for further investigation; the dose of 250 μg/kg was used as an effective therapeutic dose. Intranasal administration was the route for delivery.

Surgical Simulation of a Posttraumatic Spinal Cord Glial Scar in Rats

“…Further optimization of the local spinal cord cooling technology will involve improvements to the original cryoconductor design and optimization of lowtemperature exposure conditions. Detailed studies on animal models related to the improvement of surgical techniques and use of innovative laser-optical technologies and other techniques will bring practicing surgeons closer to solving the problem of functional recovery of the spinal cord in the posttraumatic period [14, 15, 16].…”

The use of nootropics in Alzheimer’s disease: is there light at the end of the tunnel?

“…To gain more insight into the pharmacodynamics of nootropics, recent studies on cell lines as well as review papers were also considered. Dichrocephala integrifolia improved cognitive deficits and attenuated neuronal death on scopolamine-induced mouse model of AD 43 , while Pharmaceutical substance (PhS) based on amide form Human leukemia differential factor -6 (AF HLDF-6) restores cognitive dysfunction in C57B1/6 transgenic mouse model of AD 44 . Further, fisetin reverses synaptic dysfunction, prevented neuroinflammation, and improves memory in C57BL/6N transgenic mouse model of cognitive dysfunction 45 , and Cerebrolysin showed its neuroprotective potential by protecting grafted Neural stem cells (NSCs) in an APP Transgenic mice model of AD, hence it could be a potential adjuvant therapy for AD when combined with grafting 46 .…”