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001-es BibID:BIBFORM064480
Első szerző:Zsuga Judit (neurológus, pszichoterapeuta, egészségügyi szakmanager)
Cím:FNDC5/irisin, a molecular target for boosting reward-related learning and motivation / Judit Zsuga, Gabor Tajti, Csaba Papp, Bela Juhasz, Rudolf Gesztelyi
Megjegyzések:Interventions focusing on the prevention and treatment of chronic non-communicable diseases are onrise. In the current article, we propose that dysfunction of the mesocortico-limbic reward system contributesto the emergence of the WHO-identified risk behaviors (tobacco use, unhealthy diet, physicalinactivity and harmful use of alcohol), behaviors that underlie the evolution of major noncommunicablediseases (e.g. cardiovascular diseases, cancer, diabetes and chronic respiratory diseases).Given that dopaminergic neurons of the mesocortico-limbic system are tightly associated with rewardrelatedprocesses and motivation, their dysfunction may fundamentally influence behavior. While nicotineand alcohol alter dopamine neuron function by influencing some receptors, mesocortico-limbic systemdysfunction was associated with elevation of metabolic set-point leading to hedonic over-eating.Although there is some empirical evidence, precise molecular mechanism for linking physical inactivityand mesocortico-limbic dysfunction per se seems to be missing; identification of which may contribute tohigher success rates for interventions targeting lifestyle changes pertaining to physical activity.In the current article, we compile evidence in support of a link between exercise and the mesocorticolimbicsystem by elucidating interactions on the axis of muscle ? irisin ? brain derived neurotrophic factor(BDNF) ? and dopaminergic function of the midbrain. Irisin is a contraction-regulated myokineformed primarily in skeletal muscle but also in the brain. Irisin stirred considerable interest, when itsability to induce browning of white adipose tissue parallel to increasing thermogenesis was discovered.Furthermore, it may also play a role in the regulation of behavior given it readily enters the central nervoussystem, where it induces BDNF expression in several brain areas linked to reward processing, e.g.the ventral tegmental area and the hippocampus. BDNF is a neurotropic factor that increases neuronaldopamine content, modulates dopamine release relevant for neuronal plasticity and increased neuronalsurvival as well as learning and memory. Further linking BDNF to dopaminergic function is BDNF's abilityto activate tropomyosin-related kinase B receptor that shares signalization with presynaptic dopamine-3receptors in the ventral tegmental area.Summarizing, we propose that the skeletal muscle derived irisin may be the link between physicalactivity and reward-related processes and motivation. Moreover alteration of this axis may contributeto sedentary lifestyle and subsequent non-communicable diseases. Preclinical and clinical experimentalmodels to test this hypothesis are also proposed.
Tárgyszavak:Orvostudományok Egészségtudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Medical Hypotheses 90 (2016), p. 23-28. -
További szerzők:Tajti Gábor (1988-) (gyógyszerész, biofizikus, sejtbiológus) Papp Csaba (1966-) (aneszteziológus és intenzív terápiás szakorvos) Juhász Béla (1978-) (kísérletes farmakológus) Gesztelyi Rudolf (1969-) (kísérletes farmakológus)
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