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An empirical dependence allowing one to identify rhythmic fluctuations of stable and unstable state in respect of hypoxia in the process of adaptation has been developed on the basis of long-term investigation of changes in brain content of adenine nucleotides upon "hypobaric training" of rabbits. The function approximating this dependence enables one to predict the effective number of "hypobaric training" sessions providing for the adaptive reaction. Key Words: hypoxia; AMP; ATP; energy metabolism; adaptationThe response to hypoxia of organs and tissues with intense energy metabolism (for instance, brain and muscles) has several aspects. Versatile biochemical mechanisms of this response possess characteristic differences and tissue specialization. Adenosine triphosphate is a direct energy substrate for the majority of cellular functions. Proceeding from this, it seems reasonable to suggest the balance of adenine nueleotides for the basic component in analysis of adaptive mechanisms and estimation of adaptation efficiency.The creatine kinase reaction is an extremely effective mechanism of emergency correction of ATP level upon substantial (up to 3-fold) decrease in the rate of oxygen consumption [12]; this mechanism provides for not more than 5% modulations of ATP level. Although this mechanism has limited reserves, it is associated with regulatory systems of energy metabolism (respiratory chain enzymes and reduced equivalents in the mitoehondria) operating at other levels to prevent energy deficit upon hypoxia. Since these systems are very complex, it is impossible to Department of Biochemistry, St. Petersburg University;, Department of Applied Mathematics, Nizhnii Novgorod State Technical University; Department of Biochemistry, Nizhnii Novgorod Medical Academy describe their function even with the use of a simplified kinetic model. Meanwhile, empirical dependences characterizing changes in the concentrations of adenine nucleotides, guanidine phosphates, and other energy metabolites can be employed for solution of some practical problems, for instance, for definition of criteria of the resistance to hypoxia. The set of dependencies can be varied in the search for optimal decision taking into consideration the informativeness of parameters, the difficulties of their experimental measurements, etc.The state of the adenine nucleotide system, specifically, the ATP and AMP concentrations, is a sensitive marker of brain resistance to hypoxia [I0,1 I, 13]. Is has been shown that brain ATP content decreases after "hypobaric trainings" which provide a 2-4-fold increase in the resistance to hypoxia.We studied the relationships between the coneentration of major energy metabolites (ATP, AMP, ADP, and creatine phosphate) in hypobaric hypoxia and isehemia and approximated them in an .attempt to predict the state of the brain energy metabolism.In the present work we measured brain concentrations of adenine nucleotides and obtained an empirical dependence describing changes in the AM P concentration relative to brain ATP cont...

MicroRNAs (miRNAs) are short, 22-25 nucleotide long transcripts that may suppress entire signaling pathways by interacting with the 3'-untranslated region (3'-UTR) of coding mRNA targets, interrupting translation and inducing degradation of these targets. The long 3'-UTRs of brain transcripts compared to other tissues predict important roles for brain miRNAs. Supporting this notion, we found that brain miRNAs co-evolved with their target transcripts, that non-coding pseudogenes with miRNA recognition elements compete with brain coding mRNAs on their miRNA interactions, and that Single Nucleotide Polymorphisms (SNPs) on such pseudogenes are enriched in mental diseases including autism and schizophrenia, but not Alzheimer's disease (AD). Focusing on evolutionarily conserved and primate-specifi c miRNA controllers of cholinergic signaling ('CholinomiRs'), we fi nd modifi ed CholinomiR levels in the brain and/or nucleated blood cells of patients with AD and Parkinson's disease, with treatment-related diff erences in their levels and prominent impact on the cognitive and anti-infl ammatory consequences of cholinergic signals. Examples include the acetylcholinesterase (AChE)-targeted evolutionarily conserved miR-132, whose levels decline drastically in the AD brain. Furthermore, we found that interruption of AChE mRNA's interaction with the primatespecifi c CholinomiR-608 in carriers of a SNP in the AChE's miR-608 binding site induces domino-like eff ects that reduce the levels of many other miR-608 targets. Young, healthy carriers of this SNP express 40% higher brain AChE activity than others, potentially aff ecting the responsiveness to AD's anti-AChE therapeutics, and show elevated trait anxiety, infl ammation and hypertension. Non-coding regions aff ecting miRNA-target interactions in neurodegenerative brains thus merit special attention.