Brain and plasma amino acid concentration in infant rats prenatally exposed to valproic acid
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Published on: December 14, 2014
Ángel Alberto Puig-Lagunes1, Luisa Rocha2, Consuelo Morgado-Valle1
1Centro de Investigaciones Cerebrales, Universidad Veracruzana, Médicos y Odontólogos, s/n, Col. Unidad del Bosque, 91010 Xalapa, Veracruz, México.
Insights
Prenatal exposure to valproic acid (VPA) altered brain amino acid levels in a rat model of autism. Glutamate and glutamine increased in the hippocampus, while glycine rose in the cortex.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Neurochemistry
Background:
- Autism spectrum disorder (ASD) is linked to imbalances in GABAergic and glutamatergic neurotransmission.
- Valproic acid (VPA) exposure during pregnancy is a known risk factor for ASD.
- VPA-induced animal models are crucial for studying ASD pathophysiology.
Purpose of the Study:
- To investigate the impact of prenatal VPA exposure on amino acid concentrations in specific brain regions and plasma.
- To assess changes in GABA, glutamate, glutamine, aspartate, taurine, and glycine levels.
- To utilize the VPA rat model to understand neurochemical alterations relevant to autism.
Main Methods:
- Pregnant rats received VPA or saline on embryonic day 12.
- Amino acid concentrations (GABA, glutamate, glutamine, aspartate, taurine, glycine) were measured in rat brain tissue (frontal cortex, hippocampus, amygdala, brain stem, cerebellum) and plasma.
- High-performance liquid chromatography (HPLC) coupled with fluorometric detection was employed for quantification.
Main Results:
- VPA-exposed rats showed significantly increased glutamate and glutamine concentrations in the hippocampus.
- Glycine concentration was elevated in the cortex of VPA-exposed rats.
- No significant changes in amino acid levels were observed in other brain regions or plasma.
Conclusions:
- Prenatal VPA exposure may disrupt excitatory and inhibitory neurotransmitter systems in the developing brain.
- Specific regional alterations in amino acid neurotransmitters suggest a potential mechanism underlying VPA-induced neurodevelopmental changes.
- These findings contribute to understanding the neurobiological underpinnings of autism spectrum disorder.
Abstract:
Autism spectrum disorder is associated with alterations in GABAergic and glutamatergic neurotransmission. Here, we aimed to determine the concentration of GABA, glutamate, glutamine, aspartate, taurine, and glycine in brain tissue and plasma of rats prenatally exposed to valproic acid (VPA), a well-characterized experimental model of autism. Pregnant rats were injected with VPA (600mg/Kg) during the twelfth-embryonic-day. Control rats were injected with saline. On the fourteen-postnatal-day, rats from both groups (males and females) were anesthetized, euthanized by decapitation and their brain dissected out. The frontal cortex, hippocampus, amygdala, brain stem and cerebellum were dissected and homogenized. Homogenates were centrifuged and supernatants were used to quantify amino acid concentrations by HPLC coupled with fluorometric detection. Blood samples were obtained by a cardiac puncture; plasma was separated and deproteinized to quantify amino acid concentration by HPLC. We found that, in VPA rats, glutamate and glutamine concentrations were increased in hippocampus and glycine concentration was increased in cortex. We did not find changes in other regions or in plasma amino acid concentration in the VPA group with respect to control group. Our results suggest that VPA exposure in utero may impair inhibitory and excitatory amino acid transmission in the infant brain.
