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  • Arthur posted an update 1 year ago

    Prepulse inhibition (PPI) of acoustic startle reflex is a measure of sensorimotor gating that may reflect the biological processes underlying gaiting impairments in schizophrenia. Although PPI is clinically useful, why PPI is inhibited in schizophrenia is largely unknown. Prepulse inhibition is mediated by M2-like muscarinic acetylcholine receptor on neurons in the caudal pontine reticular nucleus (PnC), activation of this receptor induces Gαi dissociation, and inhibits adenylyl cyclase, resulting in the inhibition of the neurons. On the other hand, the symptoms of schizophrenia are mainly linked to hyperactive dopaminergic activity, mediated by dopamine D2-like receptor. Interestingly, D2-like receptor also uses Gαi. This means that both M2-like acetylcholine receptor and D2-like dopamine receptor use same Gαi-protein, competitively. Thus, chronic over-activation of D2-like receptor observed in schizophrenia may disrupt normal M2-like acetylcholine receptor functions due to their shared coupling to Gαi-proteins, i.e. by reducing the amount of Gαi-protein available for M2-like acetylcholine receptors, resulting in the impairment of PPI.Blood-brain barrier (BBB) impairment clearly accelerates brain disease progression. As ways to prevent injury-induced barrier dysfunction remain elusive, better understanding of how BBB cells interact and modulate barrier integrity is needed. Our metabolomic profiling study showed that cell-specific adaptation to injury correlates well with metabolic reprogramming at the BBB. In particular we noted that primary astrocytes (AC) contain comparatively high levels of glutathione (GSH)-related metabolites compared to primary endothelial cells (EC). Injury significantly disturbed redox balance in EC but not AC motivating us to assess 1) whether an AC-EC GSH shuttle supports barrier stability and 2) the impact of GSH on EC function. Using an isotopic labeling/tracking approach combined with Time-of-Flight Mass Spectrometry (TOF-MS) we prove that AC constantly shuttle GSH to EC even under resting conditions – a flux accelerated by injury conditions in vitro. In correlation, co-culture studies revealed that blocking AC GSH generation and secretion via siRNA-mediated γ-glutamyl cysteine ligase (GCL) knockdown significantly compromises EC barrier integrity. Using different GSH donors, we further show that exogenous GSH supplementation improves barrier function by maintaining organization of tight junction proteins and preventing injury-induced tight junction phosphorylation. Thus the AC GSH shuttle is key for maintaining EC redox homeostasis and BBB stability suggesting GSH supplementation could improve recovery after brain injury.Telomerase consists of the catalytic subunit Telomerase Reverse Transcriptase (TERT) and the Telomerase RNA Component. Its canonical function is the prevention of telomere erosion. Over the last years it became evident that TERT is also present in tissues with low replicative potential. Important non-canonical functions of TERT are protection against apoptosis and maintenance of the cellular redox homeostasis in cancer as well as in somatic tissues. Intriguingly, TERT and reactive oxygen species (ROS) are interdependent on each other, with TERT being regulated by changes in the redox balance and itself controlling ROS levels in the cytosol and in the mitochondria. The latter is achieved because TERT is present in the mitochondria, where it protects mitochondrial DNA and maintains levels of anti-oxidative enzymes. Since numerous diseases are associated with oxidative stress, increasing the mitochondrial TERT level could be of therapeutic value.Background This study examined whether changes in quitting smoking differed according to smokers’ cigarettes consumed per day (CPD) and intention to quit (ITQ) after the introduction of two tobacco control measures in Korea, a tobacco tax increase in 2015 and pictorial cigarette pack warnings (PCW) in 2016. Methods We utilized data from the Korea Welfare Panel Study from 2013 to 2017, an interval that was divided into four periods (2013-2014, 2014-2015, 2015-2016, and 2016-2017). We examined differential changes in quitting smoking by smokers’ CPD and ITQ using a generalized estimating equation model. Results Smokers with 1-14 CPD or an ITQ were more likely to quit smoking in each period. However, when compared to the pre-policy period (2013-2014), smokers with 15 or more CPD and those with an ITQ had a higher risk ratio of quitting smoking in all study periods. In stratified analyses, when the tobacco excise tax was increased, the risk ratios of quitting smoking increased in most subgroups, especially smokers with 15 or more CPD or an ITQ. The increased risk ratio of 15 or more CPD smokers subgroup sustained afterward. However, after the introduction of PCW, there were no significant changes from the previous period in most subgroups. Conclusions The addictive nature of tobacco and the type of tobacco control policies jointly contributed to changes in quitting smoking among Korean smokers. Tobacco control policies, particularly substantial tobacco tax increase, acted as a cue-to-action for quitting smoking among more dependent smokers.Sex differences in cognitive functions are heavily debated. Recent work suggests that sex differences do stem from different processing strategies utilized by men and women. While these processing strategies are likely reflected in different brain networks, so far the link between brain networks and processing strategies remains speculative. In the present study we seek for the first time to link sex differences in brain activation patterns to sex differences in processing strategies utilizing a semantic verbal fluency task in a large sample of 35 men and 35 women, all scanned thrice. Zoligratinib For verbal fluency, strategies of clustering and switching have been described. Our results show that men show higher activation in the brain network supporting clustering, while women show higher activation in the brain network supporting switching. Furthermore, converging evidence from activation results, lateralization indices and connectivity analyses suggests that men recruit the right hemisphere more strongly during clustering, but women during switching.

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