A Low-Molecular-Weight BDNF Mimetic, Dipeptide GSB-214, Prevents Memory Impairment in Rat Models of Alzheimer’s Disease

Acta Naturae

article

Polina Yu. Povarnina¹  Anna A. Volkova²  Olga N. Vorontsova¹  Andrey A. Kamensky³  Tatiana A. Gudasheva¹  Sergey B. Seredenin¹ 

[1] Research Zakusov Institute of Pharmacology;Research Zakusov Institute of Pharmacology, Lomonosov Moscow State University;Lomonosov Moscow State University

关键词: brain-derived neurotrophic factor;    dimeric dipeptide mimetic;    Alzheimer’s disease;    scopolamine;    streptozotocin;    memory.;   

DOI  :  10.32607/actanaturae.11755

学科分类：生物技术

来源: Moskovskii Gosudarstvennyi Universitet im.M.V.Lomonosova/M.V.Lomonosov Moscow State University

【 摘 要 】

Brain-derived neurotrophic factor (BDNF) is known to be involved in the pathogenesis of Alzheimer’s disease (AD). However, the pharmacological use of full-length neurotrophin is limited, because of its macromolecular protein nature. A dimeric dipeptide mimetic of the BDNF loop 1, bis-(N-monosuccinyl-L-methionyl-L-serine) heptamethylene diamide (GSB-214), was designed at the Zakusov Research Institute of Pharmacology. GSB-214 activates TrkB, PI3K/AKT, and PLC-γ1 in vitro. GSB-214 exhibited a neuroprotective activity during middle cerebral artery occlusion in rats when administered intraperitoneally (i.p.) at a dose of 0.1 mg/kg and improved memory in the novel object recognition test (0.1 and 1.0 mg/kg, i.p.). In the present study, we investigated the effects of GSB-214 on memory in the scopolamine- and steptozotocin-induced AD models, with reference to activation of TrkB receptors. AD was modeled in rats using a chronic i.p. scopolamine injection or a single streptozotocin injection into the cerebral ventricles. GSB-214 was administered within 10 days after the exposure to scopolamine at doses of 0.05, 0.1, and 1 mg/kg (i.p.) or within 14 days after the exposure to streptozotocin at a dose of 0.1 mg/kg (i.p.). The effect of the dipeptide was evaluated in the novel object recognition test; K252A, a selective inhibitor of tyrosine kinase receptors, was used to reveal a dependence between the mnemotropic action and Trk receptors. GSB-214 at doses of 0.05 and 0.1 mg/kg statistically significantly prevented scopolamine-induced long-term memory impairment, while not affecting short-term memory. In the streptozotocin-induced model, GSB-214 completely eliminated the impairment of short-term memory. No mnemotropic effect of GSB-214 was registered when Trk receptors were inhibited by K252A.

【 授权许可】

Unknown