Environmental Pollution, Год журнала: 2024, Номер 362, С. 124932 - 124932
Опубликована: Сен. 13, 2024
Язык: Английский
Brain Behavior and Immunity, Год журнала: 2024, Номер 117, С. 493 - 509
Опубликована: Фев. 2, 2024
In the last years, hypothesis that elevated levels of proinflammatory cytokines contribute to pathogenesis neurodevelopmental diseases has gained popularity. IL-1 is one main found be in Autism spectrum disorder (ASD), a complex condition characterized by defects social communication and cognitive impairments. this study, we demonstrate mice lacking signaling display autistic-like associated with an excessive number synapses. We also show microglia at early stages are unable properly perform process synapse engulfment activation mammalian target rapamycin (mTOR) signaling. Notably, even acute inhibition IL-1R1 IL-1Ra sufficient enhance mTOR reduce synaptosome phagocytosis WT microglia. Finally, treatment rescues IL-1R deficient mice. These data unveil exclusive role microglial refinement via indicate novel mechanism possibly involved disorders pathway.
Язык: Английский
Процитировано
14
JAMA Pediatrics, Год журнала: 2024, Номер 178(3), С. 258 - 258
Опубликована: Янв. 22, 2024
Importance Uptake of COVID-19 vaccines among pregnant individuals was hampered by safety concerns around potential risks to unborn children. Data clarifying early neurodevelopmental outcomes offspring exposed vaccination in utero are lacking. Objective To determine whether exposure maternal associated with differences scores on the Ages and Stages Questionnaire, third edition (ASQ-3), at 12 18 months age. Design, Setting, Participants This prospective cohort study, Assessing Safety Pregnancy During Coronavirus Pandemic (ASPIRE), enrolled participants from May 2020 August 2021; follow-up children these pregnancies is ongoing. Participants, which included their all 50 states, self-enrolled online. Study activities were performed remotely. Exposure In fetus during pregnancy compared those unexposed. Main Outcomes Measures Neurodevelopmental validated ASQ-3, completed birth mothers months. A score below established cutoff any 5 subdomains (communication, gross motor, fine problem solving, social skills) constituted an abnormal screen for developmental delay. Results total 2487 (mean [SD] age, 33.3 [4.2] years) less than 10 weeks’ gestation research activities, yielding a 2261 1940 infants aged months, respectively, assessments. crude analyses, 471 1541 (30.6%) screened abnormally delay vs 203 720 unexposed (28.2%; χ 2 = 1.32; P .25); corresponding prevalences 262 1301 (20.1%) 148 639 (23.2%), respectively (χ 2.35; .13). multivariable mixed-effects logistic regression models adjusting race, ethnicity, education, income, depression, anxiety, no difference risk ASQ-3 screens observed either time point (12 months: adjusted ratio [aRR], 1.14; 95% CI, 0.97-1.33; aRR, 0.88; 0.72-1.07). Further adjustment preterm infant sex did not affect results 1.16; 0.98-1.36; 0.87; 0.71-1.07). Conclusions Relevance this study suggest that safe perspective neurodevelopment Additional longer-term should be conducted corroborate findings buttress clinical guidance strong evidence base.
Язык: Английский
Процитировано
9
Brain Behavior and Immunity, Год журнала: 2025, Номер unknown
Опубликована: Март 1, 2025
Язык: Английский
Процитировано
1
Biological Psychiatry, Год журнала: 2023, Номер 95(4), С. 348 - 360
Опубликована: Ноя. 1, 2023
Язык: Английский
Процитировано
17
Neuroscience & Biobehavioral Reviews, Год журнала: 2024, Номер 164, С. 105844 - 105844
Опубликована: Авг. 4, 2024
This systematic review explored the impact of maternal immune activation (MIA) on learning and memory behavior in offspring, with a particular focus sexual dimorphism. We analyzed 20 experimental studies involving rodent models (rats mice) exposed to either lipopolysaccharide (LPS) or POLY I:C during gestation following Preferred Reporting Items for Systematic Reviews Meta-Analyses (PRISMA) guidelines. Our findings reveal that most report detrimental MIA performance highlighting significant role prenatal environmental factors neurodevelopment. Furthermore, this underscores complex effects sex, males often exhibiting more pronounced cognitive impairment compared females. Notably, small subset enhanced function MIA, suggesting complex, context-dependent outcomes challenges. also highlights sex differences caused by terms cytokine responses, alterations gene expression, microglial responses as contribute observed.
Язык: Английский
Процитировано
6
JAMA Network Open, Год журнала: 2024, Номер 7(10), С. e2439792 - e2439792
Опубликована: Окт. 16, 2024
Importance In utero exposure to maternal infections has been associated with abnormal neurodevelopment among offspring. The emergence of a new, now endemic infection (SARS-CoV-2) warrants investigating developmental implications for exposed Objective To assess whether in COVID-19 is neurodevelopmental scores children ages 12, 18, and 24 months. Design, Setting, Participants Data were ascertained from the ASPIRE (Assessing Safety Pregnancy Coronavirus Pandemic) trial, prospective cohort pregnant individuals aged 18 years or older who enrolled before 10 weeks’ gestation their children. Individuals recruited online May 14, 2020, August 23, 2021, using Society Assisted Reproductive Technology BabyCenter, an media platform. all 50 states Puerto Rico completed activities remotely. Exposure COVID-19. Main Outcomes Measures Birth mothers Ages & Stages Questionnaires, Third Edition, validated screening tool delays, at months’ post partum. A score below cutoff any domain (communication, gross motor, fine problem-solving, social skills) was considered screen (scores range 0 60 each domain, higher indicating less risk delay). Results included 2003 (mean [SD] age, 33.3 [4.2] years) study activities; 1750 (87.4%) had earned college degree. Neurodevelopmental outcomes available 1757 age 12 months, 1522 1523 prevalence screens vs unexposed offspring months 64 198 (32.3%) 458 1559 (29.4%); 36 161 (22.4%) 279 1361 (20.5%); 29 151 (19.2%) 230 1372 (16.8%). adjusted mixed-effects logistics regression model, no difference observed (adjusted ratio [ARR], 1.07 [95% CI, 0.85-1.34]), (ARR, 1.15 0.84-1.57]), 1.01 0.69-1.48]). Supplemental analyses did not identify differential based on trimester infection, presence absence fever, breakthrough following vaccination primary infection. Conclusions Relevance this offspring, results through Continued diverse groups needed because, other factors, evidence suggests sensitivity developing fetal brain immune activation.
Язык: Английский
Процитировано
6
Brain Behavior and Immunity, Год журнала: 2024, Номер unknown
Опубликована: Ноя. 1, 2024
Язык: Английский
Процитировано
6
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Янв. 8, 2024
ABSTRACT We discovered that apocrine secretion by embryonic choroid plexus (ChP) epithelial cells contributes to the cerebrospinal fluid (CSF) proteome and influences brain development in mice. The response relies on sustained intracellular calcium signaling calpain-mediated cytoskeletal remodeling. It rapidly alters CSF proteome, activating neural progenitors lining brain’s ventricles. Supraphysiological induced during mouse maternal administration of a serotonergic 5HT2C receptor agonist dysregulates offspring cerebral cortical development, fate CSF-contacting progenitors, ultimately changes adult social behaviors. Critically, exposure illness or psychedelic drug LSD pregnancy also overactivates ChP, inducing excessive secretion. Collectively, our findings demonstrate new mechanism which diverse stressors disrupts utero development.
Язык: Английский
Процитировано
4
Current Opinion in Psychiatry, Год журнала: 2024, Номер 37(3), С. 237 - 250
Опубликована: Фев. 19, 2024
Perinatal mental health research provides an important perspective on neurobehavioral development. Here, we aim to review the association of maternal perinatal with offspring neurodevelopment, providing update (self-)regulation problems, hypothesized mechanistic pathways, progress and challenges, implications for health.
Язык: Английский
Процитировано
4
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Май 26, 2024
Prenatal infections and activation of the maternal immune system have been proposed to contribute causing neurodevelopmental disorders (NDDs), chronic conditions often linked brain abnormalities. Microglia are resident cells play a key role in neurodevelopment. Disruption microglial functions can lead abnormalities increase risk developing NDDs. How as well fetal affect human neurodevelopment NDDs remains unclear. An important reason for this knowledge gap is fact that impact exposure prenatal factors has challenging study context. Here, we characterized model cerebral organoids (CO) with integrated microglia (COiMg). These express typical markers respond inflammatory stimuli. The presence influences organoid development, including cell density neural differentiation, regulates expression several ciliated mesenchymal markers. Moreover, COiMg without show similar but also distinct responses Additionally, IFN-γ induced significant transcriptional structural changes organoids, appear be regulated by microglia. Specifically, interferon-gamma (IFN-γ) was found alter genes autism. This provides valuable tool how perturbations processes.
Язык: Английский
Процитировано
3