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It was found that GK-2 at a daily dose of 1 mg/kg, intraperitoneally, during 7 days statistically significantly reduces brain infarct volume by 20-60% at the first injection from 4 to 24h, with the highest effect 6-8 hours after surgery. Thus, the 'therapeutic window' of GK-2 detected in the experiment is no less than 24 hours, which exceeds the existing neuroprotective agents.

Based on the comorbidity of diabetes, depression, and dementia and recognizing that a deficiency of the nerve growth factor (NGF) is involved in all of these kinds of pathologies, we studied the effect of the mimetic of dimeric dipeptide NGF loop 4, GK-2, on a model of streptozotocin-induced type 2 diabetes in C57Bl/6 mice. GK-2 [hexamethylenediamide bis-(N-monosuccinyl-glutamyl-lysine)] was synthesized at the V.V. Zakusov Scientific Research Institute of Pharmacology. The study revealed the ability of GK-2 to ameliorate hyperglycemia induced by streptozotocine (STZ 100 mg/kg i.p.) in C57Bl/6 mice, to restore learning ability in the Morris Water Maze test, and to overcome depression after both intraperitoneal (0.5 mg/kg) and peroral (5 mg/kg) long-term administration. The presence of the listed properties and their preservation in the case of peroral treatment determines the prospects of research. Taking into account the previous findings on the ability of GK-2 to selectively activate PI3K/Akt, these data suggest that Akt-signaling is sufficient for pancreatic beta cell function. GK-2 has been shown to exhibit pronounced neuroprotective activity. The coexistence of neuroprotective and antidiabetic effects is in agreement with the fundamental concept holding that the function of neurons and pancreatic beta cells is controlled by similar mechanisms.

Monoamine metabolism in the hypothalamus and striatum of BALB/c and C57Bl/6 mice (intact and stressed in the open field test) was studied using single- and multidimensional statistical methods. It is suggested that the revealed difference in neurotransmitter metabolism is associated with genetically controlled behavior of these animals under conditions of emotional stress. The results of discriminant analysis suggest that the regulation of monoamine metabolism during emotional stress is genetically determined.

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