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DOI 10.1007/s10517-016-3241-5
Bulletin of Experimental Biology and Medicine, Vol. 160, No. 5, March, 2016 PHARMACOLOGY AND TOXICOLOGY
653
Neuropeptide Cycloprolylglycine Exhibits Neuroprotective Activity after Systemic Administration to Rats with Modeled Incomplete Global Ischemia and in In Vitro Modeled Glutamate Neurotoxicity
P. Yu. Povarnina, K. N. Kolyasnikova, S. V. Nikolaev*, T. A. Antipova*, and T. A. Gudasheva
Translated from Byulleten Eksperimentalnoi Biologii i Meditsiny, Vol. 160, No. 11, pp. 600-603, November, 2015 Original article submitted April 29, 2015
We studied cerebroprotective properties of neuropeptide cycloprolylglycine (1 mg/kg) administered intraperitoneally to rats with modeled incomplete global ischemia rats and neuroprotective properties for HT-22 cells under conditions of glutamate toxicity. It was shown that the neuropeptide administered during the postischemic period restored the neurological status of rats by preventing sensorimotor impairments in the limb-placing test and suppression of locomotor activity in the open eld test. In in vitro experiments, cycloprolylglycine in concentrations of 105-108 M exhibited pronounced dose-dependent neuroprotective activity. The results attest to high cerebro- and neuroprotective potential of endogenous peptide cycloprolylglycine.
Key Words: neuropeptide cycloprolylglycine; cerebroprotective activity; neuroprotective activity; incomplete global cerebral ischemia; glutamate neurotoxicity
Cycloprolylglycine neuropeptide (CPG) as an endogenous compound was discovered in rat brain in 1996 [10], but earlier CPG was designed as the dipeptide prototype of classic nootropic piracetam [1,3]. It was found that CPG is similar to piracetam not only structurally, but also by its pharmacological properties, including nootropic [4], anxiolytic [2] and antihypoxic [6] activities. Effective doses of CPG are 100-1000-fold below the doses of piracetam. Neuroprotective activity of CPG has been demonstrated in vitro in the model of 6-OHDA toxicity on SH-SY5Y cells [6] and in in vivo rat model of stroke [9]. It should be noted that CPG is the principal metabolite of the widely used nootropic dipeptide Noopept producing also neuroprotective effect [11].
Here we studied the cerebroprotective properties of CPG on rat model of incomplete global ischemia caused by irreversible bilateral occlusion of the carotid arteries. Since glutamate excitotoxicity plays the key role in the formation of lesion in cerebral ischemia, the neuroprotective properties of CPG were studied on the model of glutamate toxicity on mouse hippocampal HT-22 neurons.
MATERIALS AND METHODS
Cerebroprotective properties of CPG were evaluated on random-bred male rats weighing 250-340 g...