Striatal synaptic changes and behavior in adult mouse upon prenatal exposure to valproic acid

Hernández, Adán; Delgado‐González, Evangelina; Durairaj, Ragu Varman; Reyes‐Haro, Daniel; Martı́nez-Torres, Ataúlfo; Espinosa, Felipe Rafael Reyna

doi:10.1016/j.brainres.2023.148461

Cited by 4 publications

(2 citation statements)

References 72 publications

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“…Mouse models of VPA exposure are typically achieved through injection of VPA into a pregnant dam roughly midway through gestation, resulting in offspring that exhibit both neurodevelopmental and behavioral alterations (Roullet et al, 2013). Rotarod phenotypes across studies of VPA models vary, with some identifying enhanced rotarod performance (Hernandez et al, 2023), and others identifying no difference from WT (Gandal et al, 2010), or a deficit in the task (Wang et al, 2018), owing potentially to variability in VPA exposure protocols.…”

Section: Environmental Risk Factorsmentioning

confidence: 99%

Altered motor learning and coordination in mouse models of autism spectrum disorder

Cording,

Bateup

2023

Front. Cell. Neurosci.

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Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with increasing prevalence. Over 1,000 risk genes have now been implicated in ASD, suggesting diverse etiology. However, the diagnostic criteria for the disorder still comprise two major behavioral domains - deficits in social communication and interaction, and the presence of restricted and repetitive patterns of behavior (RRBs). The RRBs associated with ASD include both stereotyped repetitive movements and other motor manifestations including changes in gait, balance, coordination, and motor skill learning. In recent years, the striatum, the primary input center of the basal ganglia, has been implicated in these ASD-associated motor behaviors, due to the striatum’s role in action selection, motor learning, and habit formation. Numerous mouse models with mutations in ASD risk genes have been developed and shown to have alterations in ASD-relevant behaviors. One commonly used assay, the accelerating rotarod, allows for assessment of both basic motor coordination and motor skill learning. In this corticostriatal-dependent task, mice walk on a rotating rod that gradually increases in speed. In the extended version of this task, mice engage striatal-dependent learning mechanisms to optimize their motor routine and stay on the rod for longer periods. This review summarizes the findings of studies examining rotarod performance across a range of ASD mouse models, and the resulting implications for the involvement of striatal circuits in ASD-related motor behaviors. While performance in this task is not uniform across mouse models, there is a cohort of models that show increased rotarod performance. A growing number of studies suggest that this increased propensity to learn a fixed motor routine may reflect a common enhancement of corticostriatal drive across a subset of mice with mutations in ASD-risk genes.

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Section: Environmental Risk Factorsmentioning

confidence: 99%

Altered motor learning and coordination in mouse models of autism spectrum disorder

Cording,

Bateup

2023

Front. Cell. Neurosci.

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“…It is involved in synaptic recognition, specification, and functional maturation, and maintains E-I homeostasis in specific neural connections ( 79 ). One study found that mice prenatally exposed to valproic acid (VPA) exhibited cognitive and motor deficits in Y-maze learning, which may be due to reduced levels of proteins involved in excitatory synapse formation, such as Nlgn1 and PSD-95 ( 80 ). Among the subtypes of Nlgn, the Nlgn2 gene is often reduced in expression in severe neuropsychiatric disorders ( 81 ), Nlgn3 primarily mediates enteric neuron-neuroglial ( 82 ), and Nlgn4 is primarily involved in functioning in intelligence, social skills, sleep, and arousal ( 83 ) and impairments of all of these subtypes are associated with ASD.…”

Section: Neural Pathwaysmentioning

confidence: 99%

Neuroplasticity of children in autism spectrum disorder

Chen,

Wang,

Zhang

et al. 2024

Front. Psychiatry

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Autism spectrum disorder (ASD) is a neurodevelopmental disorder that encompasses a range of symptoms including difficulties in verbal communication, social interaction, limited interests, and repetitive behaviors. Neuroplasticity refers to the structural and functional changes that occur in the nervous system to adapt and respond to changes in the external environment. In simpler terms, it is the brain’s ability to learn and adapt to new environments. However, individuals with ASD exhibit abnormal neuroplasticity, which impacts information processing, sensory processing, and social cognition, leading to the manifestation of corresponding symptoms. This paper aims to review the current research progress on ASD neuroplasticity, focusing on genetics, environment, neural pathways, neuroinflammation, and immunity. The findings will provide a theoretical foundation and insights for intervention and treatment in pediatric fields related to ASD.

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Spontaneous Calcium Transients Recorded from Striatal Astrocytes in a Preclinical Model of Autism

Saavedra-Bonilla,

Varman,

Reyes-Haro

2024

Neurochem Res

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Autism spectrum disorder (ASD) is known as a group of neurodevelopmental conditions including stereotyped and repetitive behaviors, besides social and sensorimotor deficits. Anatomical and functional evidence indicates atypical maturation of the striatum. Astrocytes regulate the maturation and plasticity of synaptic circuits, and impaired calcium signaling is associated with repetitive behaviors and atypical social interaction. Spontaneous calcium transients (SCT) recorded in the striatal astrocytes of the rat were investigated in the preclinical model of ASD by prenatal exposure to valproic acid (VPA). Our results showed sensorimotor delay, augmented glial fibrillary acidic protein -a typical intermediate filament protein expressed by astrocytes- and diminished expression of GABAA-ρ3 through development, and increased frequency of SCT with a reduced latency that resulted in a diminished amplitude in the VPA model. The convulsant picrotoxin, a GABAA (γ-aminobutyric acid type A) receptor antagonist, reduced the frequency of SCT in both experimental groups but rescued this parameter to control levels in the preclinical ASD model. The amplitude and latency of SCT were decreased by picrotoxin in both experimental groups. Nipecotic acid, a GABA uptake inhibitor, reduced the mean amplitude only for the control group. Nevertheless, nipecotic acid increased the frequency but diminished the latency in both experimental groups. Thus, we conclude that striatal astrocytes exhibit SCT modulated by GABAA-mediated signaling, and prenatal exposure to VPA disturbs this tuning.

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Striatal synaptic changes and behavior in adult mouse upon prenatal exposure to valproic acid

Cited by 4 publications

References 72 publications

Altered motor learning and coordination in mouse models of autism spectrum disorder

Altered motor learning and coordination in mouse models of autism spectrum disorder

Neuroplasticity of children in autism spectrum disorder

Spontaneous Calcium Transients Recorded from Striatal Astrocytes in a Preclinical Model of Autism

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