Downregulation of the GABAA receptor β2 subunit in a rat model of autism




GABA, GABAA, Autism, Valproic acid, GARB2


Introduction: Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain, and GABA type A receptor (GABAA) activation mediates fast inhibitory actions. Numerous studies have shown that individual with autism spectrum disorder (ASD) exhibit abnormalities in the expression of GABAA receptors in various brain areas. Additionally, animal models of ASD have suggested alterations in GABAergic neurotransmission and a dysregulation in the balance between inhibitory and excitatory systems. Objective: We investigated the immunolabeling of the GABAA receptor β2 subunit (GARB2) in the hippocampus, the amygdala, and thalamus of infant rats prenatally exposed to valproic acid (VPA) as an ASD model. Methods: Pregnant females were injected with VPA (600mg/Kg, i.p.) during the twelfth embryonic day; control rats were injected with saline. On the fourteen-postnatal-day, rats from both experimental groups were anesthetized, transcardially perfused with 0.9% NaCl and 4% paraformaldehyde, and sequential coronal brain sections (40μm thickness) were obtained. Immunohistochemistry was performed to detect GARB2 and the relative optical density (OD) of expression was analyzed. Results: Our data showed a statistically significant downregulation of GARB2 in the lateral amygdaloid nucleus, as well as in the ventral and lateral thalamic nuclei when compared to control rats. No statistically significant differences were detected in the hippocampus. Discussion: Our findings suggest that prenatal exposure to VPA reduces GARB2 expression in limbic brain regions involved in social-emotional behaviors, like previous reports in individuals with ASD. Conclusion These results support for the involvement of the GABAergic system in the pathogenesis of ASD.

Author Biographies

Ángel Alberto Puig-Lagunes, Facultad de Medicina, Universidad Veracruzana

Facultad de Medicina, Universidad Veracruzana, Minatitlán, Veracruz, Mexico.

Atenas y Managua s/n Col. Nueva Mina. C.P. 96760 Minatitlán, Veracruz, Mexico.

Frida Sofía Villada, Instituto de Investigaciones Cerebrales, Universidad Veracruzana

Instituto de Investigaciones Cerebrales, Universidad Veracruzana, Xalapa, Veracruz, Mexico.

Luis Castelazo Ayala s/n, Col. Industrial Ánimas, C.P. 91190, Xalapa, Veracruz, Mexico.

Consuelo Morgado-Valle, Instituto de Investigaciones Cerebrales, Universidad Veracruzana

Instituto de Investigaciones Cerebrales, Universidad Veracruzana, Xalapa, Veracruz, Mexico.

Luis Castelazo Ayala s/n, Col. Industrial Ánimas, C.P. 91190, Xalapa, Veracruz, Mexico.

Luis Beltran-Parrazal, Instituto de Investigaciones Cerebrales, Universidad Veracruzana

Instituto de Investigaciones Cerebrales, Universidad Veracruzana, Xalapa, Veracruz, Mexico.

Luis Castelazo Ayala s/n, Col. Industrial Ánimas, C.P. 91190, Xalapa, Veracruz, Mexico.

Lizbeth Donají Chi-Castañeda, Instituto de Investigaciones Cerebrales, Universidad Veracruzana

Instituto de Investigaciones Cerebrales, Universidad Veracruzana, Xalapa, Veracruz, Mexico.

Luis Castelazo Ayala s/n, Col. Industrial Ánimas, C.P. 91190, Xalapa, Veracruz, Mexico.


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How to Cite

Puig-Lagunes, Ángel A., Villada, F. S., Morgado-Valle, C., Beltran-Parrazal, L., Chi-Castañeda, L. D., & Lopez Meraz, M. L. (2023). Downregulation of the GABAA receptor β2 subunit in a rat model of autism. Archivos De Neurociencias, 1(Inpress).



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