A hypothalamus és az autonóm idegrendszer szabályozó mechanizmusaiban részt vevő agypályák topográfiája és neurokémiai karakterizálásuk = Topography and neurochemical characterization of hypothalamic and central autonomic pathways

1. Feltérképezték a hypothalamus orexin-termelő neuronjainak agytörzsi projekcióit, pályáit, valamint elsőként mutatták ki kapcsolatait az agytörzs valamennyi noradrenalint és adrenalint termelő sejtcsoportjának neuronjaival. A vizsgálat eredménye alapvető fontosságú neuromorfológiai adat a táplálékfelvétel, valamint az agyi catecholamine rendszer kapcsolatának tisztázására a szervezet energia-háztartásának szempontjából. 2. Különböző neuroanatómiai és immunhisztokémiai vizsgálatokkal először írták le a korábban ismeretlen mediális paralemniscális magot patkány, majom és az emberi alsó agytörzsben. Igazolták egy speciális peptiderg (TIP39-PTH2 receptor) rendszer jelenlétét e mag területén. Tisztázták a magcsoport afferens és efferens neuronális kapcsolatait és adatot szolgáltattak ezen mag neuronjainak az akusztikus stresszben vitt szerepéről. 3. Igazolták egy limbikus agykéregből leszálló, a gyomor működésében szerepet vivő pálya multiszinaptikus jelenlétét és topográfiáját: infralimbic anterior cingulate cortex - centralis amygdala - paraszimpatikus dorsalis vagus mag - n. vagus pálya. 4. Elsőként írták le a ""jóllakottság"" érzés (satiety) agypályáját a gyomor - n. vagus - nucleus tractus solitariii - hypothalamus nucleus dorsomedialis. Igazolták az ezen pályán belüli szignál transzdukcióban a glucagon-like peptide-1 és a prolactin-releasing hormon neuropeptidek meghatározó szerepét. | In order to attain major objectives of the project, a number of various neuromorphological techniques have been successfully applied to identify, localize and characterize neuronal pathway that interconnect the hypothalamus and lower brainstem nuclei. The major new findings and observations are the follows: 1) Pathways and lower brainstem projections of hypothalamic orexin-expressing neurons have been verified a mapped topographically. Termination and synaptic contacts of orexin-containing fibers have been demonstrated on adrenaline- and noradrenaline-expressing neurons in each lower brainstem catecholamine cell group indicating the existence of a descending hypothalamic pathway that influence the body energy metabolism by controlling the peripheral catecholamine outflow. 2) The afferent and efferent neuronal connections of the pontine medial paralemniscal nucleus have been first described in the rat, monkey and human brains providing evidence for the hypothalamic connections of this cell group that may participate in acoustic stress response. 3) The description of a multisynaptic pathway between the limbic system and the lower brainstem autonomic centers via hypothalamus and the amygdala has been completed in the present study demonstrating the functional importance of limbic cortical areas on the functional activity of the stomach. 4) The complete neuronal pathway of the “satiety signal” from the stomach to the hypothalamic regulatory center has been first verified by demonstrating of the ascending glucagon-like peptide-1 projections from the nucleus of the solitary tract to dorsomedial hypothalamic neurons. This may represent one of the most important link in the mechanism that control the central regulation of food intake

A conserved MTMR lipid phosphatase increasingly suppresses autophagy in brain neurons during aging

Ageing is driven by the progressive, lifelong accumulation of cellular damage. Autophagy (cellular self-eating) functions as a major cell clearance mechanism to degrade such damages, and its capacity declines with age. Despite its physiological and medical significance, it remains largely unknown why autophagy becomes incapable of effectively eliminating harmful cellular materials in many cells at advanced ages. Here we show that age-associated defects in autophagic degradation occur at both the early and late stages of the process. Furthermore, in the fruit fly Drosophila melanogaster , the myotubularin-related (MTMR) lipid phosphatase egg-derived tyrosine phosphatase (EDTP) known as an autophagy repressor gradually accumulates in brain neurons during the adult lifespan. The age-related increase in EDTP activity is associated with a growing DNA N 6 -adenine methylation at EDTP locus. MTMR14, the human counterpart of EDTP, also tends to accumulate with age in brain neurons. Thus, EDTP, and presumably MTMR14, promotes brain ageing by increasingly suppressing autophagy throughout adulthood. We propose that EDTP and MTMR14 phosphatases operate as endogenous pro-ageing factors setting the rate at which neurons age largely independently of environmental factors, and that autophagy is influenced by DNA N 6 -methyladenine levels in insects