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Locus Coeruleus permanent magnet resonance image in cognitively unchanged elderly subjects.
L.P. Li, J.W. Liang and H.J. Fu. An update on the association between traumatic brain injury and Alzheimer's disease Focus on Tau pathology and synaptic dysfunction. NEUROSCI BIOBEHAV REVXXX-XXX,2020.-Traumatic brain injury (TBI) and Alzheimer's disease (AD) are devastating conditions that have long-term consequences on individual's cognitive functions. Although TBI has been considered a risk factor for the development of AD, the link between TBI and AD is still in debate. Aggregation of hyperphosphorylated tau and intercorrelated synaptic dysfunction, two key pathological elements in both TBI and AD, play a pivotal role in mediating neurodegeneration and cognitive deficits, providing a mechanistic link between these two diseases. In the first part of this review, we analyze the experimental literatures on tau pathology in various TBI models and review the distribution, biological features and mechanisms of tau pathology following TBI with implications in AD pathogenesis. In the second part, we review evidences of TBI-mediated structural and functional impairments in synapses, with a focus on the overlapped mechanisms underlying synaptic abnormalities in both TBI and AD. Finally, future perspectives are proposed for uncovering the complex relationship between TBI and neurodegeneration, and developing potential therapeutic avenues for alleviating cognitive deficits after TBI.In the present study, we wanted to review the role of cannabinoids in learning and memory in animal models, with respect to their interaction effects with six principal neurotransmitters involved in learning and memory including dopamine, glutamate, GABA (γ-aminobutyric acid), serotonin, acetylcholine, and noradrenaline. Cannabinoids induce a wide-range of unpredictable effects on cognitive functions, while their mechanisms are not fully understood. Cannabinoids in different brain regions and in interaction with different neurotransmitters, show diverse responses. Previous findings have shown that cannabinoids agonists and antagonists induce various unpredictable effects such as similar effect, paradoxical effect, or dualistic effect. Mepazine It should not be forgotten that brain neurotransmitter systems can also play unpredictable roles in mediating cognitive functions. Thus, we aimed to review and discuss the effect of cannabinoids in interaction with neurotransmitters on learning and memory. In addition, we mentioned to the type of interactions between cannabinoids and neurotransmitter systems. We suggested that investigating the type of interactions is a critical neuropharmacological issue that should be considered in future studies.Recent focus on the consequences of early life adversity (ELA) in neurobiological research led to a variety of findings suggesting alterations in several physiological systems, such as the cardiovascular system. In this systematic review and meta-analysis, we focused on the relationship between early life maltreatment (ELM), one form of ELA, and resting vagal activity indexed by resting-state heart rate variability (HRV). A systematic search of the literature yielded 1'264 hits, of which 32 studies reporting data for group comparisons or correlations were included. By quantitative synthesis of existing studies using random-effect models, we found no evidence for a relationship between ELM exposure and resting vagal activity in principal. Conducting meta-regression analyses, however, we found the relationship between ELM and resting vagal activity to significantly vary as a function of both age and the presence of psychopathology. In light of the current multitude of vastly unclear pathways linking ELM to the onset of disease, we emphasize the need for further research and outline several aspects to consider in future studies.Neuropeptide Y (NPY) is likely the main endogenous anxiolytic neuromodulator involved in alcohol intake. NPY-Y1, a receptor for NPY, is highly expressed in the periaqueductal gray (PAG), a mesencephalic structure involved in integrating nervous activity to the performance of active and passive defensive behaviors related to fear and anxiety. Interestingly, anxiety and fear are some of the prevailing emotional negative states during alcohol abstinence. Moreover, an inverse relationship between NPY activity and alcohol consumption has been frequently reported, mainly in the extended amygdala. Nevertheless, both the roles of NPY and that of the receptor involved in these actions have been scarcely studied. Thus, the aim of this study was to analyze the pharmacological effect of NPY and NPY-Y1 receptor blockade into the dorsal periaqueductal gray (D-PAG) in an alcohol consumption and relapse paradigm in adult male Wistar rats. Ninety-six rats at postnatal day 42 (PND-42) were classified as having low and high anxiety (LA and HA), respectively, through the elevated plus maze test (EPM). Then, those animals were randomly divided into alcohol naïve (AN) and forced alcohol consumption (FAC) groups. A cannula was implanted in D-PAG to microinject vehicle (VEH), NPY, or BIBP-3226 (a selective NPY-Y1 receptor antagonist). A defensive burying behavior test (DBB) was performed to assess the anxiety-like state during withdrawal, followed by a 24-hour free choice voluntary alcohol intake test. Under our experimental conditions, NPY microinjection decreased alcohol consumption in HA rats, whereas NPY-Y1 receptor blockade in D-PAG produced a notably anxiogenic effect and higher alcohol intake and relapse. In conclusion, NPY in the D-PAG, most likely acting on NPY-Y1 receptors, induced a significant anxiolytic effect and prominently inhibited alcohol consumption and relapse in Wistar rats.Myotonic dystrophy type 1 (DM1) is a debilitating multisystemic disorder, caused by expansion of a CTG microsatellite repeat in the 3' untranslated region of the DMPK (dystrophia myotonica protein kinase) gene. To date, novel therapeutic approaches have focused on transient suppression of the mutant, repeat-expanded RNA. However, recent developments in the field of genome editing have raised the exciting possibility of inducing permanent correction of the DM1 genetic defect. Specifically, repurposing of the prokaryotic CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 (CRISPR-associated protein 9) system has enabled programmable, site-specific, and multiplex genome editing. CRISPR-based strategies for the treatment of DM1 can be applied either directly to patients, or indirectly through the ex vivo modification of patient-derived cells, and they include excision of the repeat expansion, insertion of synthetic polyadenylation signals upstream of the repeat, steric interference with RNA polymerase II procession through the repeat leading to transcriptional downregulation of DMPK, and direct RNA targeting of the mutant RNA species.
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