Abstract des Autors

Serotonin (5-HT) regulates the most extensive modulatory behavioral system in the brain of vertebrates. 5-HT projections are influenced by extrinsic and intrinsic impulses from different cortical brain areas, which reach Raphe nuclei over feedback loops, containing external and internal body information about planning, evaluation, motivation, or excitation. Serotonergic neurotransmission adjusts neuromodulation with consecutive adequate stimulation of the neuronal network. This depends on appropriate equilibration of presynaptic 5-HT storage and release but also on 5-HT reuptake from synaptic cleft by 5-HT transporters. The associated pre- and postsynaptic 5-HT receptor cooperation, postsynaptic second messenger response, and phosphoinositide signaling mediated by postsynaptic 5-HT 2 receptor subpopulation alter signal transduction in which myristolated alanine rich C kinase substrate is prominently involved in regulation of further central 5-HT areas in the brain and corresponding functional neuronal changes. Even though the central function of 5-HT neurotransmission is dominating in multifold behavioral regulation, peripheral concentration of tryptophan (TRP) and TRP passage across the blood-brain barrier and TRP hydroxylase activity are also important for appropriate 5-HT neurotransmission, as they affect central 5-HT synthesis. The high adaptability of 5-HT neurotransmission is able to compensate neuromodular dysfunctions in the brain by mechanisms that mediate 5-HT biosynthesis, release, reuptake, pre-and postsynaptic receptor stimulation with the respective second messenger response, and signal transduction to various areas of the brain that are involved in regulation of behavior, mood, memory, learning, and attenuation of obsession. Adequate 5-HT system function supports regulation of intercommunicative neuronal transmission in the brain, which optimizes behavioral neuromodulation during and after transient disturbances of neuromodular behavior caused by stress-induced exertions. Impairment of neuromodulation and neuronal network in the brain with transient dysfunctions or permanent substantial deficits at manifestation of various types of depression results from prevalent impairment of 5-HT neurotransmission and its central interaction with other neurotransmitter systems. It is suggested that in overtrained athletes, central fatigue, mental deficiency, and behavioral alterations with depressive mood are probably caused by a central exhaustive exercise stress that elicits impairment of complex neuromodulation, also afflicting the interaction of central neurotransmitters or hypothalamic neuropeptides and releasing factors. This suggestion is also supported by data on alterations in 5-HT neurotransmission in eating disorders. Verf.-Referat