Multiparametric Assays Capture Sex- and Environment-Dependent Modifiers of Behavioral Phenotypes in Autism Mouse Models DOI Creative Commons
Lucas Wahl,

Arun Karim,

Amy R. Hassett

et al.

Biological Psychiatry Global Open Science, Journal Year: 2024, Volume and Issue: 4(6), P. 100366 - 100366

Published: July 20, 2024

Current phenotyping approaches for murine autism models often focus on one selected behavioral feature, making the translation onto a spectrum of autistic characteristics in humans challenging. Furthermore, sex and environmental factors are rarely considered. Here, we aimed to capture full manifestations three mouse develop "behavioral fingerprint" that takes influences under consideration. To this end, employed wide range classical standardized tests; two multi-parametric assays: Live Mouse Tracker Motion Sequencing (MoSeq), male female Shank2, Tsc1 Purkinje cell specific-Tsc1 mutant mice raised standard or enriched environments. Our aim was integrate our high dimensional data into single platform classify differences all experimental groups along dimensions with maximum discriminative power. Multi-parametric assays enabled far more accurate classification compared tests, dimensionality reduction analysis demonstrated significant additional gains accuracy, highlighting presence sex, genotype groups. Together, results provide complete phenotypic description tested groups, suggesting can entire heterogenous phenotype models.

Language: Английский

Cognitive-Affective Functions of the Cerebellum DOI Creative Commons
Stephanie Rudolph, Aleksandra Badura, Stefano Lutzu

et al.

Journal of Neuroscience, Journal Year: 2023, Volume and Issue: 43(45), P. 7554 - 7564

Published: Nov. 8, 2023

The cerebellum, traditionally associated with motor coordination and balance, also plays a crucial role in various aspects of higher-order function dysfunction. Emerging research has shed light on the cerebellum's broader contributions to cognitive, emotional, reward processes. influence autonomic further highlights its significance regulating motivational emotional states. Perturbations cerebellar development have been implicated neurodevelopmental disorders, including autism spectrum disorder attention deficit hyperactivity disorder. An increasing appreciation for neuropsychiatric symptoms that arise from dysfunction underscores importance elucidating circuit mechanisms underlie complex interactions between cerebellum other brain regions comprehensive understanding behavior. By briefly discussing new advances mapping affective, autonomic, social processing reviewing neuropathology beyond domain, this Mini-Symposium review aims provide broad perspective intersections limbic health disease.

Language: Английский

Citations

49
Cerebellum in Alzheimer's disease and other neurodegenerative diseases: an emerging research frontier DOI Creative Commons
Cui Yang, Guangdong Liu, Xi Chen

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(7)

Published: July 1, 2024

Abstract The cerebellum is crucial for both motor and nonmotor functions. Alzheimer's disease (AD), alongside other dementias such as vascular dementia (VaD), Lewy body (DLB), frontotemporal (FTD), well neurodegenerative diseases (NDs) like Parkinson's (PD), amyotrophic lateral sclerosis (ALS), Huntington's (HD), spinocerebellar ataxias (SCA), are characterized by specific non‐specific neurodegenerations in central nervous system. Previously, the cerebellum's significance these conditions was underestimated. However, advancing research has elevated its profile a critical node pathology. We comprehensively review existing evidence to elucidate relationship between aforementioned diseases. Our findings reveal growing of unequivocally establishing link AD, forms dementia, NDs, supported clinical evidence, pathological biochemical profiles, structural functional neuroimaging data, electrophysiological findings. By contrasting cerebellar observations with those from cerebral cortex hippocampus, we highlight distinct role processes. Furthermore, also explore emerging therapeutic potential targeting treatment This underscores importance diseases, offering new insights into mechanisms novel strategies.

Language: Английский

Citations

12
Cerebellar Functions Beyond Movement and Learning DOI
Linda Kim, Detlef Heck, Roy V. Sillitoe

et al.

Annual Review of Neuroscience, Journal Year: 2024, Volume and Issue: 47(1), P. 145 - 166

Published: April 25, 2024

The cerebellum has a well-established role in controlling motor functions, including coordination, posture, and the learning of skilled movements. mechanisms for how it carries out behavior remain under intense investigation. Interestingly though, recent years cerebellar function have faced additional scrutiny since nonmotor behaviors may also be controlled by cerebellum. With such complexity arising, there is now pressing need to better understand structure, function, intersect influence that are dynamically called upon as an animal experiences its environment. Here, we discuss experimental work frames possible neural shapes disparate why dysfunction catastrophic hereditary acquired conditions—both nonmotor. For these reasons, might ideal therapeutic target.

Language: Английский

Citations

10
Isolation disrupts social interactions and destabilizes brain development in bumblebees DOI Creative Commons
Z. Yan Wang, Grace C. McKenzie‐Smith, Weijie Liu

et al.

Current Biology, Journal Year: 2022, Volume and Issue: 32(12), P. 2754 - 2764.e5

Published: May 17, 2022

Language: Английский

Citations

22
Abnormal cerebellar activity and connectivity alterations of the cerebellar-limbic system in post-stroke cognitive impairment: a study based on resting state functional magnetic resonance imaging DOI Creative Commons

Haiyi Zhang,

Juan Lü, Lu Zhang

et al.

Frontiers in Neuroscience, Journal Year: 2025, Volume and Issue: 19

Published: March 19, 2025

Background Stroke is an important cause of cognitive impairment. Post-stroke impairment (PSCI) a prevalent psychiatric disorder following stroke. However, the effects PSCI on cerebellum remain mostly unknown. Methods A total 31 patients and without after stroke were included in this study. The Mini-Mental State Examination (MMSE) Montreal Cognitive Assessment (MoCA) administered to all participants. Analyses ALFF, fALFF, ReHo employed investigate alterations brain neuronal activity, while limbic connectivity analysis was utilized reflect changes within abnormal connections regions. Results We found that ALFF values increased Cerebelum_7b_R, Cerebelum_Crus1_L. fALFF Vermis_3. Cerebelum_8_R, Cerebelum_Crus2_R, functional connection between Frontal_Mid_Orb_L Cerebelum_Crus2_R regions decreased. Hippocampus_L Vermis_3 Frontal_Med_Orb_L Conclusion severity may influence extent disruption system. Furthermore, atypical activity cerebellar are associated with decline.

Language: Английский

Citations

0
DEAD‐Box Helicase 6 Blockade in Brain‐Derived Aβ Oligomers From Alzheimer's Disease Patients Attenuates Neurotoxicity DOI Creative Commons
Xiaoxu Wang, Lu Dai, Na Wu

et al.

MedComm, Journal Year: 2025, Volume and Issue: 6(5)

Published: April 24, 2025

ABSTRACT There are no effective curative treatments for Alzheimer's disease (AD), the most prevalent form of dementia. Amyloid‐beta (Aβ) oligomers considered key neurotoxic molecules that trigger AD. Recent studies have shown direct antibody targeting Aβ is beneficial early AD patients; however, serious side effects (e.g., brain hemorrhage, edema, and shrinkage) persist. Considering readily bind to other proteins, contributing neurotoxicity onset, those proteins could represent alternative therapeutic targets. However, in brains patients not yet been identified. In this study, we identified four (DDX6, DSP, JUP, HRNR) derived from patients. Intriguingly, among these only blockade DEAD‐box helicase 6 (DDX6) human‐derived attenuated their both vitro vivo. Mechanistic analysis revealed DDX6 promotes formation oligomers, likely due at distinct sites. These findings suggest serve as a potential target reduce prevent progression

Language: Английский

Citations

0
Cerebellar Purkinje Cells Control Posture in Larval Zebrafish (Danio rerio) DOI Open Access
Franziska Auer, Katherine Nardone, Kōji Matsuda

et al.

Published: Jan. 24, 2025

Cerebellar dysfunction leads to postural instability. Recent work in freely moving rodents has transformed investigations of cerebellar contributions posture. However, the combined complexity terrestrial locomotion and rodent cerebellum motivate new approaches perturb function simpler vertebrates. Here, we adapted a validated chemogenetic tool (TRPV1/capsaicin) describe role Purkinje cells — output neurons cortex as larval zebrafish swam depth. We achieved both bidirectional control (activation ablation) while performing quantitative high-throughput assessment posture locomotion. Activation modified pitch (nose-up/nose-down) axis. Similarly, ablations disrupted pitch-axis fin-body coordination responsible for climbs. Postural disruption was more widespread older larvae, offering window into emergent roles developing Finally, found that activity could individually collectively encode tilt direction, key feature neurons. Our findings delineate an expected vestibular sensation zebrafish, establishing validity TRPV1/capsaicin-mediated perturbations simple, genetically-tractable vertebrate. Moreover, by comparing cell time, uncover signatures emerging across early development. This takes major step towards understanding ancestral regulating maturation.

Language: Английский

Citations

0
Cerebellar output neurons can impair non-motor behaviors by altering development of extracerebellar connectivity DOI Creative Commons
Andrew S. Lee, Tanzil Mahmud Arefin,

Alina Gubanova

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 21, 2025

Language: Английский

Citations

0
Maternal immune activation followed by peripubertal stress combinedly produce reactive microglia and confine cerebellar cognition DOI Creative Commons
Momoka Hikosaka, Md Sorwer Alam Parvez,

Yuki Yamawaki

et al.

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: March 3, 2025

The functional alteration of microglia arises in brains exposed to external stress during early development. Pathophysiological findings neurodevelopmental disorders such as schizophrenia and autism spectrum disorder suggest cerebellar deficits. However, the link between stress-induced reactivity dysfunction is missing. Here, we investigate developmental immune environment translational mouse models that combine two risk factors: maternal infection repeated social defeat (2HIT). We find synergy inflammatory insults, leading microglial increase specifically cerebellum both sexes. Microglial turnover correlates with Purkinje neuron loss 2HIT mice. Highly multiplexed imaging-mass-cytometry identifies a cell transition TREM2(+) stress-associated cerebellum. Single-cell-proteomic clustering reveals IL-6- TGFβ-signaling association transitions. Reduced excitability remaining cells, cerebellum-involved brain-wide dysconnectivity, behavioral abnormalities indicate cognitive dysfunctions animals, which are ameliorated by systemic cerebellum-specific replacement. Early alters function, linked autism. In model, increased its turnover, causing dysfunction, was improved

Language: Английский

Citations

0
Continuous theta burst stimulation to the medial posterior cerebellum impairs reversal learning in healthy volunteers DOI Creative Commons
Eline S. Kruithof,

Eva M Drop,

Daan Gerits

et al.

Cognitive Affective & Behavioral Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

Language: Английский

Citations

0