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Neuromolecular Medicine Jun 2024Stroke is a significant public health issue, and research has consistently focused on studying the mechanisms of injury and identifying new targets. As a CDK5 activator,...
Stroke is a significant public health issue, and research has consistently focused on studying the mechanisms of injury and identifying new targets. As a CDK5 activator, p39 plays a crucial role in various diseases. In this article, we will explore the role and mechanism of p39 in cerebral ischemic injury. We measured the level of p39 using western blot and QPCR at various time points following cerebral ischemia-reperfusion (I/R) injury. The results indicated a significant reduction in the level of p39. TTC staining and behavioral results indicate that the knockout of p39 (p39KO) provides neuroprotection in the short-term. Interestingly, the behavioral dysfunction in p39KO mice was exacerbated after the repair phase of I/R. Further study revealed that this deterioration may be due to demyelination induced by elevated p35 levels. In summary, our study offers profound insights into the significance of p39 in both the acute and repair stages of ischemic injury recovery and a theoretical foundation for future therapeutic drug exploration.
Topics: Animals; Mice; Mice, Knockout; Myelin Sheath; Reperfusion Injury; Male; Mice, Inbred C57BL; Infarction, Middle Cerebral Artery; Demyelinating Diseases; Brain Ischemia; Phosphotransferases
PubMed: 38824254
DOI: 10.1007/s12017-024-08792-3 -
FASEB Journal : Official Publication of... Jun 2024Previous studies on germ-free (GF) animals have described altered anxiety-like and social behaviors together with dysregulations in brain serotonin (5-HT) metabolism....
Previous studies on germ-free (GF) animals have described altered anxiety-like and social behaviors together with dysregulations in brain serotonin (5-HT) metabolism. Alterations in circulating 5-HT levels and gut 5-HT metabolism have also been reported in GF mice. In this study, we conducted an integrative analysis of various behaviors as well as markers of 5-HT metabolism in the brain and along the GI tract of GF male mice compared with conventional (CV) ones. We found a strong decrease in locomotor activity, accompanied by some signs of increased anxiety-like behavior in GF mice compared with CV mice. Brain gene expression analysis showed no differences in HTR1A and TPH2 genes. In the gut, we found decreased TPH1 expression in the colon of GF mice, while it was increased in the cecum. HTR1A expression was dramatically decreased in the colon, while HTR4 expression was increased both in the cecum and colon of GF mice compared with CV mice. Finally, SLC6A4 expression was increased in the ileum and colon of GF mice compared with CV mice. Our results add to the evidence that the microbiota is involved in regulation of behavior, although heterogeneity among studies suggests a strong impact of genetic and environmental factors on this microbiota-mediated regulation. While no impact of GF status on brain 5-HT was observed, substantial differences in gut 5-HT metabolism were noted, with tissue-dependent results indicating a varying role of microbiota along the GI tract.
Topics: Animals; Serotonin; Mice; Male; Germ-Free Life; Behavior, Animal; Gastrointestinal Microbiome; Brain; Tryptophan Hydroxylase; Anxiety; Serotonin Plasma Membrane Transport Proteins; Mice, Inbred C57BL; Receptor, Serotonin, 5-HT1A; Colon
PubMed: 38822661
DOI: 10.1096/fj.202400334R -
AIDS and Behavior Jun 2024Evaluating routine HIV testing and treatment and use of services for people who inject drugs (PWID) is critical to curb the ongoing HIV epidemic. We analyzed data from...
Evaluating routine HIV testing and treatment and use of services for people who inject drugs (PWID) is critical to curb the ongoing HIV epidemic. We analyzed data from the 2018 National HIV Behavioral Surveillance of PWID aged 18 years or older, recruited using respondent-driven sampling and offered anonymous HIV testing after survey. We performed bivariate and multivariable analyses with log-linked Poisson regression of the generalized linear models to examine the associations between demographics and PWID service use, past-year HIV testing, and current antiretroviral therapy (ART) use. Among 10,311 HIV-negative PWID, 56% reported past-year HIV testing, and of the 553 HIV-positive PWID, 69% reported current ART use. Of the HIV-negative PWID, 64% (2874/4482) in drug treatment and 62% (3386/5440) who used syringe service programs (SSPs) reported past-year HIV testing. Among HIV-positive PWID, 75% (187/248) in drug treatment and 67% (200/298) SSP participants were on ART. In the adjusted multivariable model, past-year HIV testing was associated with drug use treatment (aPR 1.26, 95% CI 1.23-1.31) and SSP participation (aPR 1.19, 95% CI 1.13-1.26) among HIV-negative PWID. Current ART use was associated with drug use treatment (aPR 1.13, 95% CI 1.00-1.28) but the link was not significant probably due to small sample size. Findings support the expansion and improvement of PWID-targeted services, into comprehensive programs, including drug use treatment, SSP, and HIV testing and treatment.
PubMed: 38822083
DOI: 10.1007/s10461-024-04369-0 -
Nature Communications May 2024Pathologic α-synuclein (α-syn) spreads from cell-to-cell, in part, through binding to the lymphocyte-activation gene 3 (Lag3). Here we report that amyloid β...
Pathologic α-synuclein (α-syn) spreads from cell-to-cell, in part, through binding to the lymphocyte-activation gene 3 (Lag3). Here we report that amyloid β precursor-like protein 1 (Aplp1) interacts with Lag3 that facilitates the binding, internalization, transmission, and toxicity of pathologic α-syn. Deletion of both Aplp1 and Lag3 eliminates the loss of dopaminergic neurons and the accompanying behavioral deficits induced by α-syn preformed fibrils (PFF). Anti-Lag3 prevents the internalization of α-syn PFF by disrupting the interaction of Aplp1 and Lag3, and blocks the neurodegeneration induced by α-syn PFF in vivo. The identification of Aplp1 and the interplay with Lag3 for α-syn PFF induced pathology deepens our insight about molecular mechanisms of cell-to-cell transmission of pathologic α-syn and provides additional targets for therapeutic strategies aimed at preventing neurodegeneration in Parkinson's disease and related α-synucleinopathies.
Topics: alpha-Synuclein; Lymphocyte Activation Gene 3 Protein; Humans; Animals; Mice; Antigens, CD; Dopaminergic Neurons; Parkinson Disease; Protein Binding; Amyloid beta-Protein Precursor; Mice, Knockout; Male; Mice, Inbred C57BL; Female
PubMed: 38821932
DOI: 10.1038/s41467-024-49016-3 -
Trends in Molecular Medicine May 2024Neuropsychiatric symptoms (NPSs) in Alzheimer's disease (AD) constitute multifaceted behavioral manifestations that reflect processes of emotional regulation, thinking,... (Review)
Review
Neuropsychiatric symptoms (NPSs) in Alzheimer's disease (AD) constitute multifaceted behavioral manifestations that reflect processes of emotional regulation, thinking, and social behavior. They are as prevalent in AD as cognitive impairment and develop independently during the progression of neurodegeneration. As studying NPSs in AD is clinically challenging, most AD research to date has focused on cognitive decline. In this opinion article we summarize emerging literature on the prevalence, time course, and the underlying genetic, molecular, and pathological mechanisms related to NPSs in AD. Overall, we propose that NPSs constitute a cluster of core symptoms in AD, and understanding their neurobiology can lead to a more holistic approach to AD research, paving the way for more accurate diagnostic tests and personalized treatments embracing the goals of precision medicine.
PubMed: 38821772
DOI: 10.1016/j.molmed.2024.04.016 -
Psychological Reports May 2024Firearm injury is a major yet understudied public health issue in the U.S. This qualitative study explored firearm retailers' perspectives to inform messaging and...
Firearm injury is a major yet understudied public health issue in the U.S. This qualitative study explored firearm retailers' perspectives to inform messaging and communication approaches to promote firearm safety among the gun owning population. Semi-structured interviews were conducted with 17 retailers at a single gun shop in Texas. Thematic analysis identified key themes related to (1) audience segmentation, (2) appropriate use of language, and (3) trusted messengers and modalities for the communication of firearm safety information. This formative work provides practical insights to optimize public health messaging in this arena and ultimately reduce firearm injuries. Overall, this study provides valuable insights to guide the development and implementation of evidence-based, social marketing efforts aiming to promote firearm safety across various gun-owning audiences.
PubMed: 38819964
DOI: 10.1177/00332941241256880 -
Journal of Gastrointestinal Cancer May 2024This study aimed to understand how health-related quality of life (HRQoL) differs by race/ethnicity in colorectal (CRC) survivors. We aimed to 1) examine racial/ethnic...
PURPOSE
This study aimed to understand how health-related quality of life (HRQoL) differs by race/ethnicity in colorectal (CRC) survivors. We aimed to 1) examine racial/ethnic disparities in HRQoL, and 2) explore the roles of social determinants of health (SDOH) risk factors for HRQoL differ by racial/ethnic groups.
METHODS
In 2,492 adult CRC survivors using Behavioral Risk Factor Surveillance System (BRFSS) survey data (from 2014 to 2021, excluding 2015 due to the absence of CRC data), we used the Centers for Disease Control and Prevention (CDC) HRQoL measure, categorized into "better" and "poor." Multivariate logistic regressions with prevalence risk (PR) were employed for our primary analyses.
RESULTS
Compared with non-Hispanic Whites (NHW), non-Hispanic Blacks (NHB) (PR = 0.61, p = .045) and Hispanics (PR = 0.32, p < .001) reported worse HRQoL in adjusted models. In adjusted models, unemployed/retired and low-income levels were common risk factors for worse HRQoL across all comparison groups (NHW, NHB, non-Hispanic other races, and Hispanics). Other SDOH associated with worse HRQoL include divorced/widowed/never married marital status (non-Hispanic other races and Hispanics), living in rural areas (NHW and NHB), and low education levels (NHB and Hispanics). Marital status, education, and employment status significantly interacted with race/ethnicity, with the strongest interaction between Hispanics and education (PR = 2.45, p = .045) in adjusted models.
CONCLUSION
These findings highlight the need for culturally tailored interventions targeting modifiable factors (e.g., social and financial supports, health literacy), specifically for socially vulnerable CRC survivors, to address the disparities in HRQoL among different racial/ethnic groups.
PubMed: 38819610
DOI: 10.1007/s12029-024-01070-2 -
Development (Cambridge, England) Jun 2024The vertebrate Dlx gene family encode homeobox transcription factors that are related to the Drosophila Distal-less (Dll) gene and are crucial for development. Over the... (Review)
Review
The vertebrate Dlx gene family encode homeobox transcription factors that are related to the Drosophila Distal-less (Dll) gene and are crucial for development. Over the last ∼35 years detailed information has accrued about the redundant and unique expression and function of the six mammalian Dlx family genes. DLX proteins interact with general transcriptional regulators, and co-bind with other transcription factors to enhancer elements with highly specific activity in the developing forebrain. Integration of the genetic and biochemical data has yielded a foundation for a gene regulatory network governing the differentiation of forebrain GABAergic neurons. In this Primer, we describe the discovery of vertebrate Dlx genes and their crucial roles in embryonic development. We largely focus on the role of Dlx family genes in mammalian forebrain development revealed through studies in mice. Finally, we highlight questions that remain unanswered regarding vertebrate Dlx genes despite over 30 years of research.
Topics: Animals; Prosencephalon; Homeodomain Proteins; Transcription Factors; Gene Expression Regulation, Developmental; Humans; Mammals; Mice
PubMed: 38819455
DOI: 10.1242/dev.202684 -
Genetics in Medicine : Official Journal... May 2024KBG syndrome (KBGS) is a rare neurodevelopmental syndrome caused by haploinsufficiency of ANKRD11. The childhood phenotype is extensively reported but limited for...
PURPOSE
KBG syndrome (KBGS) is a rare neurodevelopmental syndrome caused by haploinsufficiency of ANKRD11. The childhood phenotype is extensively reported but limited for adults. Thus, we aimed to delineate the clinical features of KBGS.
METHODS
We collected physician-reported data of adults with molecularly confirmed KBGS through an international collaboration. Moreover, we undertook a systematic literature review to determine the scope of previously reported data.
RESULTS
The international collaboration identified 36 adults from 31 unrelated families with KBGS. Symptopms included mild/borderline intellectual disability (n=22); gross and/or fine motor difficulties (n=15); psychiatric and behavioral comorbidities including aggression, anxiety, reduced attention span, and autistic features (n=26); nonverbal (n=3), seizures with various seizure types and treatment responses (n=10); ophthalmological comorbidities (n=20). Cognitive regression during adulthood was reported once. Infrequent features included dilatation of the ascending aorta (n=2) and autoimmune conditions (n=4). Education, work, and residence varied and the diversity of professional and personal roles highlighted the range of abilities seen. The literature review identified 154 adults reported across the literature, and we have summarized the features across both datasets.
CONCLUSION
Our study sheds light on the long-term neurodevelopmental outcomes, seizures, behavioral and psychiatric features, and education, work, and living arrangements for adults with KBGS.
PubMed: 38818797
DOI: 10.1016/j.gim.2024.101170 -
The British Journal of Nutrition May 2024Essential minerals are cofactors for synthesis of neurotransmitters supporting cognition and mood. An 8-week fully-blind RCT of multinutrients for ADHD demonstrated...
Essential minerals are cofactors for synthesis of neurotransmitters supporting cognition and mood. An 8-week fully-blind RCT of multinutrients for ADHD demonstrated three times as many children (age 6-12) had significantly improved behavior ("treatment responders") on multinutrients (54%) compared to placebo (18%). The aim of this secondary study was to evaluate changes in fasted plasma and urinary mineral concentrations following the intervention, and their role as mediators and moderators of treatment response. Fourteen essential or trace minerals were measured in plasma and/or urine at baseline and week 8 from 86 participants (49 multinutrient, 37 placebo). Two-sample t-tests/Mann-Whitney U-tests compared 8-week change between treatment and placebo groups, which were also evaluated as potential mediators. Baseline levels were evaluated as potential moderators, using logistic regression models with clinical treatment response as the outcome. After 8 weeks, plasma boron, chromium (in females only), lithium, molybdenum, selenium, and vanadium, and urinary iodine, lithium, and selenium increased more with multinutrients than placebo, while plasma phosphorus decreased. These changes did not mediate treatment response. However, baseline urinary lithium trended toward moderation: participants with lower baseline urinary lithium were more likely to respond to multinutrients (p=0.058). Additionally, participants with higher baseline iron were more likely to be treatment responders regardless of treatment group (p=0.036.) These results show that multinutrient treatment response among children with ADHD is independent of their baseline plasma mineral levels, while baseline urinary lithium levels show potential as a non-invasive biomarker of treatment response requiring further study.
PubMed: 38818718
DOI: 10.1017/S0007114524001132