RESUMO
Tryptophan hydroxylase 2 (Tph-2) is the key enzyme in serotonin biosynthesis. Serotonin is one of the main neurotransmitters involved in the regulation of various physiological functions and behavior patterns. The influence of chronic ethanol consumption on the expression of the Bdnf, Bax, Bcl-xL, and CASP3 genes was studied in the brain structures of B6-1473C (C/C) and B6-1473G (G/G) mice that had been obtained on the base of the C57BL/6 strain. The strains differed in the genotype for the C1473G single nucleotide polymorphism in the Tph-2 gene and in Tph-2 enzyme activity. It was found that chronic alcohol treatment led to a significant increase in the expression of the Bdnf gene in the midbrain of B6-1473G mice, but not in B6-1473С. Chronic alcohol treatment considerably decreased the expression of the ultimate brain apoptosis effector, caspase 3, in the frontal cortex, but increased it in the hippocampus of B6-1473G mice. At the same time, chronic ethanol administration reduced the level of the antiapoptotic Bcl-xL mRNA in the midbrain of B6-1473C mice. Thus, the C1473G polymorphism in the Tph-2 gene considerably influenced the changes in the expression patterns of genes involved in the regulation of neurogenesis and neural apoptosis induced by chronic ethanol treatment.
Assuntos
Alcoolismo/genética , Fator Neurotrófico Derivado do Encéfalo/biossíntese , Caspase 3/biossíntese , Triptofano Hidroxilase/genética , Proteína X Associada a bcl-2/biossíntese , Proteína bcl-X/biossíntese , Alcoolismo/patologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Caspase 3/genética , Etanol/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Serotonina/biossíntese , Triptofano Hidroxilase/biossíntese , Proteína X Associada a bcl-2/genética , Proteína bcl-X/genéticaRESUMO
Results are presented from experimental studies of the initiation of combustion in a stoichiometric methane-oxygen mixture by a freely localized laser spark and by a high-current multispark discharge in a closed chamber. It is shown that, preceding the stage of 'explosive' inflammation of a gas mixture, there appear two luminous objects moving away from the initiator along an axis: a relatively fast and uniform wave of 'incomplete combustion' under laser spark ignition and a wave with a brightly glowing plasmoid behind under ignition from high-current slipping surface discharge. The gas mixtures in both the 'preflame' and developed-flame states are characterized by a high degree of ionization as the result of chemical ionization (plasma density n(e)≈10(12) cm(-3)) and a high frequency of electron-neutral collisions (ν(en)≈10(12) s(-1)). The role of chemical ionization in constructing an adequate theory for the ignition of a gas mixture is discussed. The feasibility of the microwave heating of both the preflame and developed-flame plasma, supplementary to a chemical energy source, is also discussed.
RESUMO
OBJECTIVE: To evaluate therapeutic effects of navigational dual-target high-frequency rTMS over the primary motor (M1, bilateral) and the left dorsolateral prefrontal cortex (DLPFC) on clinical dynamics of Parkinson's disease (PD) symptoms in a parallel placebo-controlled study. MATERIAL AND METHODS: The study included 46 patients randomized into equal therapeutic and placebo rTMS groups. Navigational therapeutic and placebo10 Hz rTMS was applied over the M1 and DLPFC areas (20 daily sessions, for 3 weeks). Assessment of the dynamics of clinical symptoms was performed using the MDS UPDRS scale (Parts I-IV) before the first session, immediately after 20 sessions, and 4-6 weeks after the rTMS course. Non-motor and mental symptoms were assessed using the Hamilton Depression Rating Scale (HDRS-17), Beck depression inventory (BDI-II), Depression, Anxiety and Stress (DASS-21) scales and the Mini Mental State Examination (MMSE). RESULTS: Significant therapeutic effects of rTMS compared to placebo were established: a greater decrease in overall score on the MDS-UPDRS scale (parts I-IV), a decrease in the severity of non-motor (part I) and motor symptoms (part III, with a large therapeutic effect for the symptoms of rigidity, bradykinesia and postural instability), as well as the severity of motor complications of dopamine replacement therapy (part IV). The effects of rTMS on motor symptoms persisted 4 weeks after the end of the stimulation course. It is also important to note significant positive dynamics in both rTMS and placebo groups in the form of comparable reduction in the severity of everyday motor symptoms (MDS-UPDRS part II), improvement of the total scores on MMSE, HDRS, BDI-II, DASS-21. CONCLUSIONS: The dual-target high-frequency rTMS over the primary motor cortex (bilateral) and the left dorsolateral prefrontal cortex has positive therapeutic effects on the motor and affective symptoms of Parkinson's disease, which are significantly stronger than that of the placebo stimulation.