Author/Authors :
Bogachouk, A.P Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry - Russian Academy of Sciences, Russia , Storozheva, Z.I V. Serbsky Federal Medical Research Center of Psychiatry and Narcology - Ministry of Health, Russia , Telegin, G.B Branch of the Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry - Russian Academy of Sciences, Russia , Chernov, A.S Branch of the Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry - Russian Academy of Sciences, Russia , Proshin, A.T Anokhin Institute of Normal Physiology - Russian Academy of Sciences, Russia , Sherstnev, V.V Anokhin Institute of Normal Physiology - Russian Academy of Sciences, Russia , Zolotarev, Yu.a no Affiliation , Lipkin, V.M Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry - Russian Academy of Sciences, Russia
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 sub-stance (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.
Keywords :
transgenic mice , Alzheimer’s disease , neuroprotective and nootropic activ-ities , amide form of HLDF-6 peptide , Differentiation factor HLDF
