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Bulletin of Experimental Biology and Medicine, Vol. 152, No. 3, January, 2012
313
PHARMACOLOGY AND TOXICOLOGY
Mechanisms of Action of Ladasten: Activation of Gene Expression for Neurotrophinsand Mitogen-Activated Kinases
M. Kh. Salimgareeva, R. S. Yamidanov, Yu. V. Vakhitova, and S. B. Seredenin*
Translated from Byulleten Eksperimentalnoi Biologii i Meditsiny, Vol. 152, No. 9, pp. 281-285, September, 2011 Original article submitted April 18, 2010
We studied the effects of single treatment with ladasten (50 mg/kg) on the content of effector kinases of the mitogen-activated cascade (ERK1/ERK2), pERK1/ERK2 activity (Thr202/ Tyr204), and expression of genes for neurotrophic factors BDND and NGF in the striatum, hypothalamus, and hippocampus of rats.
Key Words: ladasten; NGF; BDNF; gene expression; mitogen-activated kinases ERK1/2
Ladasten (N-(2-adamantyl)-N-(p-bromophenyl)-amine) was synthesized at the V. V. Zakusov Institute of Pharmacology. Experimental and clinical studies showed that this compound has a well-balanced activity (stimulatory and selective anxiolytic effects) [3]. The pharmacological effect of ladasten is manifested in the increase in physical and mental activity, deceleration of fatigue, rapid recovery of activity, and improvement of mnesic performance and learning. La dasten has a positive effect on cognitive functions (violated in somatogenic asthenia). This drug is effective in the therapy of asthenic depressions [2].
A large body of evidence exists that the effects of various psychopharmacological agents are related to the inuence on neurotrophic factors and associated systems of intracellular signaling (e.g., mitogen-activated signal cascades). Antidepressants that belong to a group of selective serotonin reuptake inhibitors (uoxetine and reboxetine) increase the content of BDNF mRNA,
BDNF protein, and TrkB receptor in the hippocampus [14]. Lithium and sodium valproate contribute to neurogenesis in the hippocampus of adult rats, which is associated with their effect on the expression of BDNF mRNA and BDNF protein and further activation of ERK signaling [6]. Moreover, typical (haloperidol) and atypical neuroleptics (clozapine, olanzapine, and risperidon) affect growth factors and their receptors (e.g., modulate the expression of BDNF, neurotrophin-3, TrkB, and TrkC) in brain structures of rats. The neuroprotective effect of long-term treatment with atypical neuroleptics is partially mediated by neurotrophins [10].
Here we studied the effect of ladasten on gene expression for neurotrophins BDNF and NGF in various brain structures. We evaluated whether mitogen-activated protein-kinases (MAP-kinases) are involved in the mechanisms of intracellular signal...