Notes

Contemporary Surgical, Oncological, and Tactical Link between Pancreaticoduodenectomy regarding Periampullary Tumours: a 5-Year Experience through Tertiary Cancers Middle.
ELS had no effect on basal respiration in either sex at either age. In contrast, ELS increased OXPHOS capacity in juvenile males and females, and reduced OXPHOS capacity in adult females but not adult males. A similar pattern of ELS-induced changes was observed for complex I activity. check details These data suggest that initial adaptations in juvenile hippocampus due to ELS were not sustained in adults. Mitochondrial adaptations to ELS were also exhibited peripherally by liver. Overall, the temporal distinctions in mitochondrial responses to ELS show that ELS-generated adaptations and outcomes are complex over the lifespan. This may contribute to differences in the timing of appearance of mental and physical disturbances, as well as potential sex differences that influence only select outcomes.Childhood maltreatment, which can take the form of physical or psychological abuse, is experienced by more than a quarter of all children. Early life stress has substantial and long-term consequences, including an increased risk of drug abuse and psychiatric disorders in adolescence and adulthood, and this risk is higher in women than in men. The neuronal mechanisms underlying the influence of early life adversities on brain functioning remain poorly understood; therefore, in the current study, we used maternal separation (MS), a rodent model of early-life neglect, to verify its influence on the properties of neurons in the ventral tegmental area (VTA), a brain area critically involved in reward and motivation processing. Using whole-cell patch-clamp recordings in brain slices from adolescent female Sprague-Dawley rats, we found an MS-induced increase in the excitability of putative dopaminergic (DAergic) neurons selectively in the medial part of the VTA. We also showed an enhancement of excitatory synaptic transmission in VTA putative DAergic neurons. MS-induced alterations in electrophysiology were accompanied by an increase in the diameter of dendritic spine heads on lateral VTA DAergic neurons, although the overall dendritic spine density remained unchanged. Finally, we reported MS-related increases in basal plasma ACTH and corticosterone levels. These results show the long-term consequences of early life stress and indicate the possible neuronal mechanisms of behavioral disturbances in individuals who experience early life neglect.The existence of a proportional relationship between the number of early-life stress (ELS) events experienced and the impoverishment of child mental health has been hypothesized. However, different types of ELS experiences may be associated with different neuro-psycho-biological impacts, due to differences in the intrinsic nature of the stress. DNA methylation is one of the molecular mechanisms that have been implicated in the "translation" of ELS exposure into neurobiological and behavioral abnormalities during adulthood. Here, we investigated whether different ELS experiences resulted in differential impacts on global DNA methylation levels in the brain and blood samples from mice and humans. ELS exposure in mice resulted in observable changes in adulthood, with exposure to social isolation inducing more dramatic alterations in global DNA methylation levels in several brain structures compared with exposure to a social threatening environment. Moreover, these two types of stress resulted in differential impacts on the epigenetic programming of different brain regions and cellular populations, namely microglia. In a pilot clinical study, blood global DNA methylation levels and exposure to childhood neglect or abuse were investigated in patients presenting with major depressive disorder or substance use disorder. A significant effect of the mental health diagnosis on global methylation levels was observed, but no effect of either childhood abuse or neglect was detected. These findings demonstrate that different types of ELS have differential impacts on epigenetic programming, through DNA methylation in specific brain regions, and that these differential impacts are associated with the different behavioral outcomes observed after ELS experiences.Taking hormonal contraceptives (HCs) affects the magnitude of the hormonal stress response and cognition. HCs are usually administered in a monthly cycle with both synthetic-hormone-containing and synthetic-hormone-absent phases. The synthetic hormones contained in HCs affect a wide range of neurophysiological systems, suggesting that effects of the medication might only be observed during the synthetic-hormone-containing phase of the HC cycle. To test this, women were seen twice, once during the hormone-present phase and once during the hormone-absent phase of the HC cycle. In each session, women performed an n-back working memory task to assess pre-stress performance outside of the magnetic resonance imaging scanner, were then exposed to cold pressor stress, and again completed the n-back task during functional magnetic resonance imaging. link2 The free cortisol response to stress remained the same across the HC cycle. Women also performed comparably on the n-back task after stress exposure across the two phases. However, despite these similarities, women displayed greater disengagement of default mode network as task demands increased during the hormone-present phase only, a pattern more in line with working memory-related brain activation under non-stressful conditions reported in other studies. The results suggest that the synthetic hormones contained in HCs may mitigate stress-related disruptions of typical brain activation patterns during the hormone-present phase of the HC cycle, despite exhibiting comparable cortisol responses across the HC cycle. Additional research is required to determine the mechanisms contributing to, and the extent of, such mitigating effects.Studies demonstrate a role for the bed nucleus of the stria terminalis (BNST) in modulating affective behavior and stress-reward integration. To explore the dynamic nature of in vivo BNST activity associated with anxiety-like behavior in a stress-inducing context, we utilized fiber photometry and detected BNST calcium transients in mice during the novelty-suppressed feeding task (NSFT). Phasic BNST activity emerged time-locked to novel object or food pellet approach during NSFT. The parabrachial nucleus (PBN) has a large input to the BNST and is thought to function as a danger signal, in arousal responses and in feeding behavior. To explore a potential role for the PBN as a contributor to BNST activity in NSFT, we investigated whether chemogenetic regulation of PBN activity altered the dynamic BNST response synchronized to NSFT approach behavior. We found that activation of the hM3D(Gq) DREADD in the PBN enhanced the observed transient signal in the BNST synchronized to the consummatory food approach, and was together these data demonstrate phasic BNST activity at a global and cell-specific level that is driven in part by PBN activity at the time of NSFT consummatory approach behavior.Previously, a sub-population of defeated anesthetized rats (Dlow) was characterized by persistent low blood levels of brain-derived neurotrophic factor (BDNF) at day 29 and autonomic alteration at day 30 after social challenge, while the other population (Dhigh) was similar to non-defeated (ND) animals. The aims of this study were to determine the time-course of autonomic dysfunction in awake animals, and whether Dhigh and/or Dlow were vulnerable to cardiac events. link3 Defeated animals were exposed to four daily episodes of social defeats from day 1 to day 4. At day 30, anesthetized Dlow displayed decreased experimental and spontaneous reflex responses reflecting lower parasympathetic efficiency. In addition, Dlow but not Dhigh were characterized by left ventricular hypertrophy at day 30. Telemetric recordings revealed that Dlow had increased low frequency-to-high frequency ratio (LF/HF) and diastolic (DBP) and systolic (SBP) blood pressure, associated with decreased HF and spontaneous baroreflex responses (BRS) from day 3 to day 29. LF/HF, DBP and SBP recovered at day 5, and HF and BRS recovered at day 15 in Dhigh. Ventricular premature beats (VPBs) occurred in Dlow and Dhigh animals from day 5. Time course of VBP fluctuations in Dhigh mirrored that of HF and BRS, but not that of LF/HF, DBP and SBP. These results suggest that a psychosocial stress associated to low serum BDNF levels can lead to vulnerability to persistent autonomic dysfunction, cardiac hypertrophy and ventricular ectopic beats. The parasympathetic recovery seen in Dhigh may provide protection against cardiac events in this population.
Multiple sclerosis (MS) is characterized by two neuropathological key aspects inflammation and neurodegeneration. Clinical studies support a prospective link between psychological stress and subsequent inflammatory disease activity. However, it is unknown if a similar link exists for grey matter (GM) degeneration as the key driver of irreversible disability.

We tested whether neural network activity triggered in a psychological fMRI stress paradigm (a mental arithmetic task including social evaluation) conducted at a baseline time point predicts future GM atrophy in 25 persons with MS (14 females). Atrophy was determined between the baseline and a follow-up time point with a median delay of 1012 (Rg 717-1439) days. Additionally, atrophy was assessed in 22 healthy subjects (13 females; median delay 771 [Rg 740-908] days between baseline and follow-up) for comparison.

An analysis of longitudinal atrophy in patients revealed GM loss in frontal, parietal, and cerebellar areas. Cerebellar atrophy was more prsease factor.MicroRNAs (miRNAs) are noncoding RNAs that participate in the pathophysiology of depression by targeting many functional genes. As shown in our previous study, chronic stress up-regulates miR-34a in the hippocampus. However, little is known about the mechanism by which miR-34a regulates the process of depression or its functions as an antidepressant by regulating its targets. In the present study, the dynamic alterations in miR-34a expression and the mechanism underlying miR-34a regulation were assessed after the administration of the antidepressant fluoxetine to mice exposed to chronic stress. In addition, the effects of miR-34a inhibition on mice were directly evaluated. Both lipopolysaccharide (LPS) and corticosterone treatment caused depression-like symptoms and increased miR-34a expression. Additionally, the expression of miR-34a, which was regulated by tropomyosin receptor kinase B (TrkB)/MEK1/ERK signaling, was consistent with the onset of action of fluoxetine. A luciferase reporter assay identified synaptotagmin-1 and Bcl-2 as the targets of miR-34a. Moreover, a miR-34a antagomir exerted antidepressant-like effects, activated TrkB/MEK1/ERK signaling and improved spine morphology in the hippocampus. In conclusion, hippocampal miR-34a overexpression was a typical feature in depression-like animals, and miR-34a downregulation exerts antidepressant-like effects by restoring the spine morphology through its target synaptotagmin-1.Early life stress paradigms have become prominent in the animal literature to model atypical development. Currently, two models have prevailed within the literature (1) limited bedding or nesting and (2) maternal separation or deprivation. Both models have produced aberrations spanning behavior and neural circuitry. Surprisingly, these two models have yet to be directly compared. The current study utilized delay eyeblink conditioning, an associative learning task with a well-defined cerebellar circuit, to compare the behavioral effects of standard limited bedding (postnatal day 2-9, n = 15) and maternal separation (60 min per day during postnatal day 2-14, n = 13) early life stress paradigms. Animals in all groups exhibited robust learning curves. Surprisingly, facilitated conditioning was observed in the maternal separation group. Rats that underwent limited bedding did not differ from the control or maternal separation groups on any conditioning measures. This study contributes to a clearer understanding of early life stress paradigms and the claims made about their mechanisms, which if better clarified can be properly leveraged to increase translational value.
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