Increased Serotonin Levels and Unchanged Glutamate and GABA Levels in Thalamic Microdialysates Despite Reduced Cell Numbers in a Valproic Acid-Induced Autism Model

Autism spectrum disorders (ASDs) are increasingly prevalent neurodevelopmental disorders characterized by deficits in social skills, abnormal sensory responses and a loss of neuronal cells. A key factor in these differences is thought to be an imbalance between excitation and inhibition. The aim of...

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Veröffentlicht in:Neurochemical research 2025-02, Vol.50 (1), p.45, Article 45
Hauptverfasser: Ay, Hakan, Horata, Erdal, Öncü Kaya, Elif Mine, Korkmaz, Orhan Tansel
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description Autism spectrum disorders (ASDs) are increasingly prevalent neurodevelopmental disorders characterized by deficits in social skills, abnormal sensory responses and a loss of neuronal cells. A key factor in these differences is thought to be an imbalance between excitation and inhibition. The aim of this study was to measure the levels of γ-aminobutyric acid (GABA), glutamate (GLU) and serotonin (5-HT) in the thalamus of a rat valproic acid (VPA)-induced ASD model and to correlate these levels with the number of thalamic cells. Ten pregnant Wistar rats were injected with 600 mg/kg VPA on Day 12.5 of gestation, whereas five control rats received saline. After the behavioral tests, the male pups were divided into ASD and control groups with ten animals each. At 55 days of age, pups underwent microdialysis under anesthesia, and thalamic samples were analyzed for GABA, GLU and 5-HT levels by ultrahigh-performance liquid chromatography (UHPLC). After microdialysis, the brain sections were stained, and the volumes of the thalamus and hemispheres were calculated using the Cavalieri method, with the number of neurons and glia determined using the optical fractionator method. Compared with the control group, the ASD group presented increased 5-HT levels, an increased hemispheric volume, a decreased thalamic volume and decreased numbers of thalamic neurons and glia. A negative correlation was observed between the GLU content and glial number in the control group but not in the ASD group. These results indicate a disturbed thalamic neurotransmitter balance. We suggest that the increased thalamic 5-HT levels in ASD rats indicates that 5-HT reuptake is inhibited by the GLU content, which remains unchanged, despite the reduced cell number.
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subjects Anesthesia
Animal models
Animals
Autism
Autism Spectrum Disorder - chemically induced
Autism Spectrum Disorder - metabolism
Autistic Disorder - chemically induced
Autistic Disorder - metabolism
Autistic Disorder - pathology
Biochemistry
Biomedical and Life Sciences
Biomedicine
Cell Biology
Cell Count
Cell number
Cerebral hemispheres
Disease Models, Animal
Disorders
Female
gamma-Aminobutyric Acid - metabolism
Glutamic Acid - metabolism
Hemispheres
Juveniles
Liquid chromatography
Male
Microdialysis
Neurochemistry
Neurodevelopmental disorders
Neurology
Neuronal-glial interactions
Neurons
Neurons - drug effects
Neurons - metabolism
Neurons - pathology
Neurosciences
Pregnancy
Rats
Rats, Wistar
Sensory evaluation
Serotonin
Serotonin - metabolism
Thalamus
Thalamus - drug effects
Thalamus - metabolism
Thalamus - pathology
Valproic Acid
γ-Aminobutyric acid
title Increased Serotonin Levels and Unchanged Glutamate and GABA Levels in Thalamic Microdialysates Despite Reduced Cell Numbers in a Valproic Acid-Induced Autism Model
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