Deep Phosphoproteome Landscape of Interhemispheric Functionality of Neuroanatomical Regions of the Human Brain.

Post-translational modifications (PTMs) are one of the compulsive and predominant biological processes that regulate the diverse molecular mechanism, modulate the onset of disease, and are the reason behind the functional diversity of proteins. Despite the widespread research findings in neuroproteomics, one of the key drawbacks has been the lack of proteome-level knowledge of hemispheric lateralization. We have investigated the proteome level expression in different neuroanatomical regions under the Human Brain Proteome Project (HBPP) and developed the global interhemispheric brain proteome map (Brainprot) earlier. Furthermore, this study has extended to decipher the phosphoproteome map of human brain interhemispheric regions through high-resolution mass spectrometry. The phosphoproteomics examination of 12 unique interhemispheric neurological brain regions using Orbitrap fusion liquid chromatography with tandem mass spectrometry provided comprehensive coverage of 996 phosphoproteins, 2010 phosphopeptides, and 3567 phosphosites. Moreover, interhemispheric phosphoproteome profiling has been categorized according to synaptic ontologies and interhemispheric expression to understand the functionality. Finally, we have integrated the phosphosites data under the PhosphoMap section in the Inter-Hemispheric Brain Proteome Map Portal (https://www.brainprot.org/) for the advancement and support of the ongoing neuroproteomics research worldwide. Data is available via ProteomeXchange with the identifier PXD031188.

Neuroanatomical regions associated with non-progressive dysarthria post-stroke: a systematic review.

BACKGROUND: Dysarthria is a common and persisting sequela to stroke. It can have a negative influence on psychological wellbeing, and quality of life. This systematic review aimed to describe and identify the neuroanatomical regions associated with non-progressive dysarthria following stroke. METHODS: A systematic search of PubMed, Ovid Medline, CINAHL, Cochrane, Scopus, and ScienceDirect was conducted to identify all relevant articles published in peer-reviewed journals up to December 2021. Following data extraction, the National Institutes of Health (NIH) quality assessment tools were used to evaluate the methodological quality of the included studies. RESULTS: Out of 2186 papers found in the literature related to dysarthria post-stroke, 24 met the inclusion criteria. Eligible articles assessed 1150 post-stroke subjects. Out of them, 420 subjects had dysarthria from isolated lesions. Regarding dysarthric subjects with ischemic strokes, 153 sustained supratentorial infarctions, while 267 had infratentorial infarctions. The majority had pontine infarctions (n = 142), followed by infarctions in the corona radiata (n = 104), and the cerebellum (n = 64). CONCLUSION: This systematic review is the first step toward establishing a neuroanatomical model of dysarthria throughout the whole brain. Our findings have many implications for clinical practice and provide a framework for implementing guidelines for early detection and management of dysarthria post-stroke.

Deciphering the Interregional and Interhemisphere Proteome of the Human Brain in the Context of the Human Proteome Project.

This study, which performs an extensive mass spectrometry-based analysis of 19 brain regions from both left and right hemispheres, presents the first draft of the human brain interhemispheric proteome. This high-resolution proteomics data provides comprehensive coverage of 3300 experimentally measured (nonhypothetical) proteins across multiple regions, allowing the characterization of protein-centric interhemispheric differences and synapse biology, and portrays the regional mapping of specific regions for brain disorder biomarkers. In the context of the Human Proteome Project (HPP), the interhemispheric proteome data reveal specific markers like chimerin 2 (CHN2) in the cerebellar vermis, olfactory marker protein (OMP) in the olfactory bulb, and ankyrin repeat domain 63 (ANKRD63) in basal ganglia, in line with regional brain transcriptomes mapped in the Human Protein Atlas (HPA). In addition, an in silico analysis pipeline was used to predict the structure and function of the uncharacterized uPE1 protein ANKRD63, and parallel reaction monitoring (PRM) was applied to validate its region-specific expression. Finally, we have built the Interhemispheric Brain Proteome Map (IBPM) Portal (www.brainprot.org) to stimulate the scientific community's interest in the brain molecular landscape and accelerate and support research in neuroproteomics. Data are available via ProteomeXchange with identifier PXD019936.

Sexual Differences in Internet Gaming Disorder (IGD): From Psychological Features to Neuroanatomical Networks.

Internet gaming disorder (IGD) has been included in the 2013 Diagnostic and Statistical Manual of Mental Disorders (DSM-5) as a condition in need of further study, and gaming disorder was recognized by the World Health Organization as a mental disorder in the International Classification of Disease (ICD-11) of 2018. IGD has different characteristics in the two sexes and is more prevalent in males than females. However, even if the female gamer population is constantly growing, the majority of available studies analyzed only males, or the data were not analyzed by sex. To better elucidate sex differences in IGD, we selectively reviewed research publications that evaluated IGD separately for males and females collected in approximately one hundred publications over the past 20 years. The available data in this narrative review indicate that IGD is strongly dimorphic by sex for both its psychological features and the involvement of different brain areas. Impulsivity, low self-control, anxiety, emotion dysregulation, and depression are some of the psychological features associated with IGD that show a sex dimorphism. At the same time, IGD and its psychological alterations are strongly correlated to dimorphic functional characteristics in relevant brain areas, as evidenced by fMRI. More research is needed to better understand sex differences in IGD. Animal models could help to elucidate the neurological basis of this disorder.

Regional heterogeneity in mitochondrial function underlies region specific vulnerability in human brain ageing: Implications for neurodegeneration.

Selective neuronal vulnerability (SNV) of specific neuroanatomical regions such as frontal cortex (FC) and hippocampus (HC) is characteristic of age-associated neurodegenerative diseases (NDDs), although its pathogenetic basis remains unresolved. We hypothesized that physiological differences in mitochondrial function in neuroanatomical regions could contribute to SNV. To investigate this, we evaluated mitochondrial function in human brains (age range:1-90 y) in FC, striatum (ST), HC, cerebellum (CB) and medulla oblongata (MD), using enzyme assays and quantitative proteomics. Striking differences were noted in resistant regions- MD and CB compared to the vulnerable regions- FC, HC and ST. At younger age (25 ± 5 y), higher activity of electron transport chain enzymes and upregulation of metabolic and antioxidant proteins were noted in MD compared to FC and HC, that was sustained with increasing age (≥65 y). In contrast, the expression of synaptic proteins was higher in FC, HC and ST (vs. MD). In line with this, quantitative phospho-proteomics revealed activation of upstream regulators (ERS, PPARα) of mitochondrial metabolism and inhibition of synaptic pathways in MD. Microtubule Associated Protein Tau (MAPT) showed overexpression in FC, HC and ST both in young and older age (vs. MD). MAPT hyperphosphorylation and the activation of its kinases were noted in FC and HC with age. Our study demonstrates that regional heterogeneity in mitochondrial and other cellular functions contribute to SNV and protect regions such as MD, while rendering FC and HC vulnerable to NDDs. The findings also support the "last in, first out" hypothesis of ageing, wherein regions such as FC, that are the most recent to develop phylogenetically and ontogenetically, are the first to be affected in ageing and NDDs.