Circuit mechanisms underlying sexually dimorphic outcomes of early life stress DOI Creative Commons
Cheng Jiang,

Ignacio Ruiz-Sanchez,

Claudia De Mei

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 28, 2024

ABSTRACT Stress during early life influences brain development and can affect social, motor, emotional processes. We describe a striking sex difference in the effects of stress (ELS), which produces anhedonia anxiety-like behaviors female adolescent mice, as reported previously, but repetitive behavioral pathology social deficits male mice. Notably, this parallels differences seen prevalence psychiatric symptoms: depression anxiety disorders are more common girls women, whereas neurodevelopmental like autism spectrum disorder Tourette syndrome markedly boys men. characterized ELS on medial prefrontal cortex (mPFC) its projections to dorsal striatum (dStr) lateral septum (LS). males, not females, developed hyperactivity cortico-striatal circuit hypoactivity cortico-septal circuit. Chemogenetic manipulation projection neurons modulates stressed females. Activation rescues males. conclude that sexually dimorphic effects, with potential relevance human symptoms, through differential circuits.

Язык: Английский

Striatal insights: a cellular and molecular perspective on repetitive behaviors in pathology DOI Creative Commons

Charlotte Lauren Burton,

A Longaretti,

Andjela Zlatanovic

и другие.

Frontiers in Cellular Neuroscience, Год журнала: 2024, Номер 18

Опубликована: Март 27, 2024

Animals often behave repetitively and predictably. These repetitive behaviors can have a component that is learned ingrained as habits, which be evolutionarily advantageous they reduce cognitive load the expenditure of attentional resources. Repetitive also conscious deliberate, may occur in absence habit formation, typically when are feature normal development children, or neuropsychiatric disorders. They considered pathological interfere with social relationships daily activities. For instance, people affected by obsessive-compulsive disorder, autism spectrum Huntington’s disease Gilles de la Tourette syndrome display wide range symptoms like compulsive, stereotyped ritualistic behaviors. The striatum nucleus basal ganglia proposed to act master regulator these through its circuit connections sensorimotor, associative, limbic areas cortex. However, precise mechanisms within striatum, detailing compartmental organization, cellular specificity, intricacies downstream connections, remain an area active research. In this review, we summarize evidence across multiple scales, including circuit-level, cellular, molecular dimensions, elucidate striatal underpinning offer perspectives on implicated We consider close relationship between behavioral output transcriptional changes, thereby structural alterations, those occurring epigenetic processes.

Язык: Английский

Процитировано

6

Dopamine Dysregulation in Reward and Autism Spectrum Disorder DOI Creative Commons
Kenneth Blum, Abdalla Bowirrat,

Keerthy Sunder

и другие.

Brain Sciences, Год журнала: 2024, Номер 14(7), С. 733 - 733

Опубликована: Июль 22, 2024

Autism spectrum disorder (ASD) is primarily characterized by core deficits in social skills, communication, and cognition repetitive stereotyped behaviors. These manifestations are variable between individuals, ASD pathogenesis complex, with over a thousand implicated genes, many epigenetic factors, multiple environmental influences. The mesolimbic dopamine (DA) mediated brain reward system held to play key role, but the rapidly expanding literature reveals intricate, nuanced signaling involving wide array of loci, neurotransmitters receptor subtypes, neuronal variants. How altered DA may constitute downstream convergence manifold causal origins not well understood. A clear working framework help delineate common stages potential diagnostic interventional opportunities. Hence, we summarize known natural history context emerging data perspectives update signaling. Then, against this backdrop, proffer provisional that organizes into successive levels, including (1) genetic changes, (2) disrupted pathways, (3) dysregulated neurotransmitter/DA signaling, finally, (4) neurocognitive behavior possible antagonist/agonist based interventions. This subdivision logical progression potentially addressable parts facilitate rational formulation diagnostics targeted treatments.

Язык: Английский

Процитировано

6

A network meta-analysis of non-invasive brain stimulation interventions for autism spectrum disorder: Evidence from randomized controlled trials DOI Creative Commons
Yang‐Chieh Brian Chen, Hsiang‐Yuan Lin, Liang‐Jen Wang

и другие.

Neuroscience & Biobehavioral Reviews, Год журнала: 2024, Номер 164, С. 105807 - 105807

Опубликована: Июль 7, 2024

The efficacy and acceptability of various non-invasive brain stimulation (NIBS) interventions for autism spectrum disorder remain unclear. We carried out a systematic review randomized controlled trials (RCTs) regarding NIBS reducing autistic symptoms (INPLASY202370003). Sixteen articles (N = 709) met the inclusion criteria network meta-analysis. Effect sizes were reported as standardized mean differences (SMDs) or odds ratios with 95 % confidence intervals (CIs). Fourteen active interventions, including transcranial direct current (tDCS), repetitive magnetic stimulation, pulse analyzed. Only anodal tDCS over left dorsolateral prefrontal cortex paired cathodal an extracephalic location (atDCS_F3 + ctDCS_E) significantly improved compared to sham controls (SMD - 1.40, %CIs 2.67 0.14). None markedly social-communication restricted/repetitive behaviors in participants. Moreover, no exhibited significant dropout rate controls, serious adverse events any intervention.

Язык: Английский

Процитировано

3

Autism spectrum disorder and various mechanisms behind it DOI

Parisa Rajabi,

Ali Sabbah Noori,

Javad Sargolzaei

и другие.

Pharmacology Biochemistry and Behavior, Год журнала: 2024, Номер 245, С. 173887 - 173887

Опубликована: Окт. 6, 2024

Язык: Английский

Процитировано

3

Habenula alterations in resting state functional connectivity among autistic individuals DOI Creative Commons

Chloe L. Hampson,

Julio A. Peraza, Laura Guerrero‐Latorre

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Май 14, 2025

The reward-based theoretical framework of autism suggests that altered reward circuitry contributes to core symptoms. Recent prior research has revealed autism-related structural alterations in the habenula, a small epithalamic structure associated with motivation and emotion; however, potential functional connectivity (FC) remain unexplored. Anatomical resting state magnetic resonance imaging (rs-fMRI) data were accessed for 1,584 participants (N=705 autism; mean age: 16.26 ± 8.15 years) Autism Brain Imaging Data Exchange (ABIDE). To investigate habenula alterations, we conducted whole-brain FC analysis, followed by regression analyses explore age brain-behavior interactions. Across entire sample, extensive was observed within midbrain dopaminergic system. Compared neurotypical (NT) controls, autistic exhibited significantly increased habenular right middle temporal gyrus bilateral superior gyri. From childhood early adulthood, adolescents, inversely decreased NTs, left culmen parahippocampus. Between groups, hyperconnectivity behavioral scores social motivation, executive functioning, daily living skills, but not communication. This study provides novel evidence autism, highlighting atypical auditory cortex. Further findings suggest develops differently among links between adaptive behaviors. Taken together, these results contribute emerging system may play critical role pathophysiology autism.

Язык: Английский

Процитировано

0

Pilot Study of Personalized Transcranial Magnetic Stimulation with Spectral Electroencephalogram Analyses for Assessing and Treating Persons with Autism DOI Open Access

Milan Makale,

Chad Nybo, Kenneth Blum

и другие.

Journal of Personalized Medicine, Год журнала: 2024, Номер 14(8), С. 857 - 857

Опубликована: Авг. 12, 2024

Autism spectrum condition (ASC) is a neurodevelopmental that only partly responsive to prevailing interventions. ASC manifests core challenges in social skills, communication, and sensory function by repetitive stereotyped behaviors, along with imbalances the brain’s excitatory (E) inhibitory (I) signaling. Repetitive transcranial magnetic stimulation (rTMS) has shown promise may be useful addition applied behavioral analysis (ABA), gold-standard psychotherapeutic intervention. We report an open-label clinical pilot (initial) study which ABA-treated persons (n = 123) received our personalized rTMS protocol (PrTMS). PrTMS uses low TMS pulse intensities continuously updates multiple cortical locales frequencies based on spectral EEG psychometrics. No adverse effects developed, 44% of subjects had scale scores reduced below diagnostic cutoffs. Importantly, responders, regression flattened, implying more balanced E/I ratio. Moreover, older participants, alpha peak frequency increased, positive correlate non-verbal cognition. effective intervention, offering improved cognitive overall symptomatology. This warrants further research into mechanisms specific types who benefit, validation present results exploration broader applicability.

Язык: Английский

Процитировано

1

Structure of subcortico-cortical tracts in middle-aged and older adults with autism spectrum disorder DOI
Michaela Cordova, Janice Hau,

Adam Schadler

и другие.

Cerebral Cortex, Год журнала: 2024, Номер 34(12)

Опубликована: Дек. 1, 2024

Abstract Middle-aged and older adults with autism spectrum disorder may be susceptible to accelerated neurobiological changes in striato- thalamo-cortical tracts due combined effects of typical aging existing disparities present from early neurodevelopment. Using magnetic resonance imaging, we employed diffusion-weighted imaging automated tract-segmentation explore tract microstructure volume differences between autistic (n = 29) comparison 33) (40 70 years old). Fractional anisotropy, mean diffusivity, volumes were measured for 14 striato-cortical 12 bundles. Data examined using linear regressions group by age plus effects, false discovery rate correction was applied. Following correction, thalamocortical premotor, pericentral, parietal regions significantly reduced compared groups, but no interactions found. Uncorrected results suggested additional main might both diffusivity across multiple subcortico-cortical tracts. Results indicate parallel rather than during adulthood those relative peers though are the most reliable.

Язык: Английский

Процитировано

1

Genetic liability underlying reward-related comorbidity in psychiatric disorders involves the coincident functions of autism–linked ADGRL1 and hevin DOI
Kerlys G. Correoso‐Braña, Augusto Anésio, Sylvie Dumas

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 5, 2024

ABSTRACT Comorbidity between psychiatric traits is thought to involve overlapping pleiotropic effects from sets of genes. Notably, substance abuse a shared comorbid condition among various neurodevelopmental disorders with externalizing symptoms such as autism spectrum disorder and attention-deficit hyperactivity disorder, thus hinting at the nucleus accumbens (NAc) site for predisposition underlying convergence genetic influences in reward-related comorbidity. Here, we identify autism-related gene encoding adhesion G protein-coupled receptor (aGPCR) Latrophilin-1/ADGRL1 an essential transducer reward mechanisms NAc. We found that ADGRL1 mRNA ubiquitously expressed throughout major NAc neuronal populations mice. A mouse model pan-neuronal Adgrl1 deficiency displayed cocaine-seeking impairments adult individuals denoting its role drug-induced reinforcement reward. Connecting molecular pathways cocaine-induced learning, uncover constitutes functional cocaine effector molecule hevin/SPARCL1. Indeed, hevin interacts membrane-expressed induces internalization while stabilizing uncleaved fraction. Moreover, alters formation intercellular contacts mediated by Neurexin-1. Importantly, constitutive coupling protein selectively modulated stimulation bias toward Gi3, Gs, G13 proteins. These findings unveil dual risk factors both define etiology

Язык: Английский

Процитировано

0

Circuit mechanisms underlying sexually dimorphic outcomes of early life stress DOI Creative Commons
Cheng Jiang,

Ignacio Ruiz-Sanchez,

Claudia De Mei

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 28, 2024

ABSTRACT Stress during early life influences brain development and can affect social, motor, emotional processes. We describe a striking sex difference in the effects of stress (ELS), which produces anhedonia anxiety-like behaviors female adolescent mice, as reported previously, but repetitive behavioral pathology social deficits male mice. Notably, this parallels differences seen prevalence psychiatric symptoms: depression anxiety disorders are more common girls women, whereas neurodevelopmental like autism spectrum disorder Tourette syndrome markedly boys men. characterized ELS on medial prefrontal cortex (mPFC) its projections to dorsal striatum (dStr) lateral septum (LS). males, not females, developed hyperactivity cortico-striatal circuit hypoactivity cortico-septal circuit. Chemogenetic manipulation projection neurons modulates stressed females. Activation rescues males. conclude that sexually dimorphic effects, with potential relevance human symptoms, through differential circuits.

Язык: Английский

Процитировано

0