Both Basal and Acute Restraint Stress-Induced c-Fos Expression Is Influenced by Age in the Extended Amygdala and Brainstem Stress Centers in Male Rats

The hypothalamus-pituitary-adrenal axis (HPA) is the main regulator of the stress response. The key of the HPA is the parvocellular paraventricular nucleus of the hypothalamus (pPVN) controlled by higher-order limbic stress centers. The reactivity of the HPA axis is considered to be a function of age, but to date, little is known about the background of this age-dependency. Sporadic literature data suggest that the stress sensitivity as assessed by semi-quantitation of the neuronal activity marker c-Fos may also be influenced by age. Here, we aimed at investigating the HPA activity and c-Fos immunoreactivity 2 h after the beginning of a single 60 min acute restraint stress in eight age groups of male Wistar rats. We hypothesized that the function of the HPA axis (i.e., pPVN c-Fos and blood corticosterone (CORT) level), the neuronal activity of nine stress-related limbic areas (i.e., magnocellular PVN (mPVN), medial (MeA), central (CeA), basolateral nuclei of the amygdala, the oval (ovBNST), dorsolateral (dlBNST), dorsomedial (dmBNST), ventral and fusiform (fuBNST) divisions of the bed nucleus of the stria terminalis (BNST)), and two brainstem stress centers such as the centrally projecting Edinger-Westphal nucleus (cpEW) and dorsal raphe nucleus (DR) show age dependency in their c-Fos response. The somatosensory barrel cortex area (S1) was evaluated to test whether the age dependency is specific for stress-centers. Our results indicate that the stress-induced rise in blood CORT titer was lower in young age reflecting relatively low HPA activity. All 12 stress-related brain areas showed c-Fos response that peaked at 2 months of age. The magnitude of c-Fos immunoreactivity correlated negatively with age in seven regions (MeA, CeA, ovBNST, dlBNST, dmBNST, fuBNST and pPVN). Unexpectedly, the CeA, ovBNST and cpEW showed a considerable basal c-Fos expression in 1-month-old rats which decreased with age. The S1 showed a U-shaped age-related dynamics in contrast to the decline observed in stress centers. We conclude that the age- and brain area dependent dynamics in stress-induced neuronal activity pattern may contribute to the age dependance of the stress reactivity. Further studies are in progress to determine the neurochemical identity of neurons showing age-dependent basal and/or stress-induced c-Fos expression

Az iszkémiás és posztiszkémiás vaszkuláris és kardiorespiratorikus károsodások tanulmányozása = Investigation of apparent injury in the vascular and cardiorespiratory system due to ischemia and reperfusion

((1) A szívhipertrófiát irányító GATA-4 transzkripciós faktort a mitogén-aktiválta protein kinázok (p38, ERK) aktiválják mechanikai feszítés során. (2) Kamrai falfeszülés az endogén endothelin-1 és az angiotenzin II révén váltja ki a BNP expressziójának fokozódását. (3) Az endogén ouabain-szerű anyag szerepet játszik az ANP bal kamrai génexpressziójának szabályozásában. (4) A nukleáris faktor-kappaB transzkripciós faktor gátlása kivédi a bal kamrai remodellinget annak előrehaladott fázisában. (5) A szívizom-kontraktilitás szabályozásában döntő szerepet játszanak a mitogén aktiválta protein kinázok. (6) Viabilitás, coronária occlusios idő okozta bal kamra funkció változás vizsgálata MRI-vel. Az occlusios idő 45 és 90 perc között változtatvan proporcionálisan rontotta a bal kamra funkciót, mely mögött okként az arányos infarctus méret áll. (7) Humán mitrokondriumok nem termelnek relevans mennyiségű nitrogén oxidot iszkémiás szívbetegekben. (8) A flavonoid szupplementáció előnyös hatású krónikus obstruktív tüdőbetegségben. (9) Invazív módon validáltuk az artériás stifness meghatározására szolgáló non-invazív Arteriográf készüléket. (10) Jellemeztük a szérum asszimmetrikus dimetil-arginin változását katéteres revascularizatios eljáráson átesett betegeknél. (11) A poli-ADP-ribóz polimeráz enzim gátlása javítja a bal kamrai funkciót akut és krónikus experimentális szívelégtelenségben. (12) A szívritmus variabilitás vizsgálatára hatékony elemző rendszert fejlesztettünk ki. | (1) Our results suggest that the prohypertrophic transcription factor GATA-4 is activated by mitogen-activated protein kinases (p38, ERK) in response to mechanical stretch. (2) Stretch-induced activation of B-type natriuretic peptid gene expression is regulated by endogenous endothelin-1 and angiotensin II. (3) Adrenal-derived endogenous ouabain-like compound is involved in the activation of atrial natriuretic peptide in the left ventricle. (4) Inhibition of nuclear factor kappa-B attenuates severe left ventricular remodeling. (5) Mitogen-activated protein kinases play pivotal role in the regulation of myocardial contractility. (6) MRI study of LV function: dependence on coronary occlusion time and viability. Occlusion time between 45 and 60 minutes induced larger infarct and consequent heart failure proportionally. (7) Human heart mitochondria do not produce physiologically relevant quantities of nitric oxide. (8) Dietary flavonoids are beneficial in chronic obstructive pulmonary disease. (9) A new, oscillometric, portable device for measuring augmentation index and aortic pulse wave velocity (Areteriograph) has been validated invasively. (10) The response of asymetric dimethylarginine levels to stent placement has been characterized in patients with coronary heart disease. (11) Inhibition of poly(ADP-ribose) polymerase improves cardiac function in acute and chronic heart failure. (12) A data analysis system has been developed for analysis of heart rate variability

VEZF1 elements mediate protection from DNA methylation

There is growing consensus that genome organization and long-range gene regulation involves partitioning of the genome into domains of distinct epigenetic chromatin states. Chromatin insulator or barrier elements are key components of these processes as they can establish boundaries between chromatin states. The ability of elements such as the paradigm β-globin HS4 insulator to block the range of enhancers or the spread of repressive histone modifications is well established. Here we have addressed the hypothesis that a barrier element in vertebrates should be capable of defending a gene from silencing by DNA methylation. Using an established stable reporter gene system, we find that HS4 acts specifically to protect a gene promoter from de novo DNA methylation. Notably, protection from methylation can occur in the absence of histone acetylation or transcription. There is a division of labor at HS4; the sequences that mediate protection from methylation are separable from those that mediate CTCF-dependent enhancer blocking and USF-dependent histone modification recruitment. The zinc finger protein VEZF1 was purified as the factor that specifically interacts with the methylation protection elements. VEZF1 is a candidate CpG island protection factor as the G-rich sequences bound by VEZF1 are frequently found at CpG island promoters. Indeed, we show that VEZF1 elements are sufficient to mediate demethylation and protection of the APRT CpG island promoter from DNA methylation. We propose that many barrier elements in vertebrates will prevent DNA methylation in addition to blocking the propagation of repressive histone modifications, as either process is sufficient to direct the establishment of an epigenetically stable silent chromatin stat