401 0007-4888/02/13340401$27.00 © 2002 Plenum Publishing Corporation MORPHOLOGY AND PATHOMORPHOLOGY Trophic Effects of Nootropic Peptide Preparations Cerebrolysin and Semax on Cultured Rat Pheochromocytoma E. R. Safarova, S. I. Shram, I. A. Grivennikov, and N. F. Myasoedov Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 133, No. 4, pp. 462-465, April, 2002 Original article submitted December 11, 2001 Trophic characteristics of neuroprotectors cerebrolysin and semax were evaluated by their capacity to induce differentiation and improve survival of cultured rat pheochromocytoma (PC12) cells. Morphological signs of cell differentiation (enlargement and formation of pro- cesses) were seen 24 h after addition of cerebrolysin into culture medium. Cerebrolysin im- proved survival of PC12 cells in serum-free medium. In a concentration of 100 μg/ml cere- brolysin decreased the content of apoptotic cells from 32% (control) to 10%. Semax produced no trophic effect on PC12 cells. Hence, the neuroprotective effect of cerebrolysin in vivo prob- ably results from trophic activity, while the protective effects of semax are mediated by oth- er mechanisms. Key Words: Key Words: Key Words: Key Words: Key Words: neuroprotection; trophic factors; cerebrolysin; semax; PC12 rat pheochromo- cytoma cell culture Institute of Molecular Genetics, Russian Academy of Sciences, Moscow. Address for correspondence: Address for correspondence: Address for correspondence: Address for correspondence: Address for correspondence: shram@img.ras.ru. Shram S. I. Many neurological and mental diseases are associated with neuronal death. Neuroprotective therapy in these diseases is aimed at prevention of nerve tissue dam- age. Some neuroprotectors were introduced into clini- cal practice, but the search of new drugs is in progress. Neuroprotective preparations include glutamate recep- tor blockers, antioxidants, and drugs with neurotrophic and neuromodulatory effects. Studies on cultured neu- ronal cell provide important information about the mechanisms of neuroprotector effects. Cerebrolysin (CL) and semax are used in the treat- ment of patients with memory and locomotor disor- ders resulting from encephalopathies of different ge- nesis. These drugs are often used in neuroprotective therapy of ischemic stroke in the acute period and du- ring rehabilitation [3]. Both these peptide preparations exhibit pronounced nootropic effects. CL is a protein hydrolysate of porcine brain consisting of free amino acids (85%) and peptides with molecular weights be- low 10 kD (15%). Neuroprotective activity of CL in ischemic stroke is determined by its capacity to im- prove neuronal survival during ischemia/reperfusion and protect neurons from toxic effects of glutamate [10,14]. Semax was developed at the Institute of Mo- lecular Genetics of the Russian Academy of Sciences [5]. Semax is a synthetic heptapeptide Met-Glu-His- Phe-Pro-Gly-Pro, an analog of the adrenocorticotropic hormone fragment (ACTH 4-10 ). Semax improves ani- mal survival under conditions of hypoxia [4]. Com- plex clinical studies demonstrated high efficiency of semax at early stages of ischemic stroke. Semax pro- moted recovery of impaired neurological functions and improved of electrophysiological parameters of the brain in patients with ischemic stroke [2]. Experiments on primary neuronal cultures showed that CL and semax possess trophic effects [1,8]. We investigated trophic properties of nootropic peptide preparations CL and semax on cultured rat pheochro- mocytoma (PC12) cells. These cells express receptors to nerve growth factor (NGF) and can differentiate into neuron-like cells in the presence of NGF [7]. This Bulletin of Experimental Biology and Medicine, Vol. 133, No. 4, April, 2002