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

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

Publication date: Nov 01, 2024

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 GABA-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 GABA (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 GABA-mediated signaling, and prenatal exposure to VPA disturbs this tuning.

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Concepts Keywords
Astrocytes Animals
Autism Astrocytes
Calcium Autism
Diminished Autism Spectrum Disorder
Prenatal Autistic Disorder
Calcium
Calcium
Calcium Signaling
Calcium signaling
Corpus Striatum
Disease Models, Animal
Female
GABA
Glial cells
Male
Picrotoxin
Picrotoxin
Pregnancy
Rats
Rats, Wistar
Striatum
Valproic Acid
Valproic Acid
Valproic acid

Semantics

Type Source Name
drug DRUGBANK Calcium
disease MESH Autism
disease MESH Autism spectrum disorder
drug DRUGBANK Valproic Acid
drug DRUGBANK gamma-Aminobutyric acid
drug DRUGBANK Picrotoxin
pathway REACTOME Dopamine receptors
disease MESH obsessive compulsive disorder
drug DRUGBANK Inositol
drug DRUGBANK Water
drug DRUGBANK Glycine
drug DRUGBANK Sucrose
drug DRUGBANK Edetic Acid
drug DRUGBANK Tromethamine
drug DRUGBANK ATP
drug DRUGBANK Sodium bicarbonate
drug DRUGBANK Dextrose unspecified form
drug DRUGBANK Potassium Chloride
drug DRUGBANK Proline
disease MESH compulsive behaviors
drug DRUGBANK Ilex paraguariensis leaf
drug DRUGBANK Trestolone
disease MESH Rett syndrome
drug DRUGBANK Esomeprazole
pathway REACTOME Reproduction
drug DRUGBANK Nandrolone phenpropionate
disease MESH syndrome
drug DRUGBANK Isoxaflutole
drug DRUGBANK Indoleacetic acid
disease MESH hypertrophy
disease MESH Neurodevelopmental disorders
drug DRUGBANK Guanosine
drug DRUGBANK L-Valine
disease MESH neuroinflammation
disease MESH astrogliosis
disease MESH Disease Models Animal

Original Article

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