Comparative Study of the Mnemotropic Activity of Dimeric Dipeptide Mimetics of Individual NGF and BDNF Loops Using a New-Object Recognition Test in Rats

Volkova, A A; Povarnina, P. Yu.; Nikiforov, D. M.; Гудашева, Татьяна Александровна; Seredenin, S. B.

doi:10.1007/s11094-022-02656-5

Cited by 5 publications

(4 citation statements)

References 31 publications

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“…The dipeptide GSB-214 eliminated only long-term memory impairment, while having no effect on short-term memory. This finding agrees with our earlier data obtained under physiological conditions in the novel object recognition test [ 22 ]. We assume that the revealed effect of GSB-214 can be attributed to the activation of the PI3K/Akt post-receptor signaling pathway, which was demonstrated earlier in in vitro experiments [ 10 ].…”

Section: Discussionsupporting

confidence: 94%

“…GSB-214 eliminated this impairment. Since no effect of GSB-214 on short-term memory under physiological conditions was observed previously [ 22 ], it is fair to assume that memory was recovered due to the increase in neuronal viability under the exposure to streptozotocin-induced toxicity. The neuroprotective effects of GSB-214 were revealed earlier in in vitro experiments [ 15 ], as well as in a rat model of ischemic stroke induced by transient middle cerebral artery oc clusion [ 16 ].…”

Section: Discussionmentioning

confidence: 87%

“…Earlier, we had found that a single-dose BDNF dipeptide mimetic GSB-214 administered i.p. (0.1 and 1.0 mg/kg) had a favorable effect on the long-term memory of rats in the novel object recognition test [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…injection of K252A (100 μg/kg) in 1% DMSO or 1% DMSO. The novel object recognition test was started after 24 h. The dose of GSB-214 was chosen based on earlier experiments [ 22 ].…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2023

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Brain-derived neurotrophic factor (BDNF) is known to be involved in the pathogenesis of Alzheimers 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-1 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.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

“…injection of K252A (100 μg/kg) in 1% DMSO or 1% DMSO. The novel object recognition test was started after 24 h. The dose of GSB-214 was chosen based on earlier experiments [ 22 ].…”

Section: Methodsmentioning

confidence: 99%

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