TABLE 2.
Alterations of the GABA system in pharmacological models of ASD.
| Pharmacological models | Method | GABA-related mechanisms | Main findings | Reference |
|---|---|---|---|---|
| VPA models | C57BL/6 mice (E 10.5 500 mg/kg i.p. injection | Number of GABAergic neurons | PV-positive GABAergic neurons were reduced in the neocortex | Gogolla et al. (2009) |
| BALB/c mice (E 12.5 600 mg/kg i.p. injection) | GABA-related proteins | Excitatory synaptic proteins NR2A, NR2B, NR2C, and inhibitory-related proteins GAD65, GAD67, GABRA1, GABRA5, and GABRB2 were downregulated | Chau et al. (2017) | |
| Rats (E12.5 600 mg/kg i.p. injection | GABA-related proteins | GAD65, GAD67, and GAT1 were evaluated in the amygdala; GAD65 and GAD67 mRNA were decreased in the cerebellum | Olexová et al. (2016) | |
| Sprague–Dawley rats (E12.5 600 mg/kg i.p. injection | GABA-related proteins | GAD67 was decreased in HP and cerebellum, and temporal cortex, and was increased in PFC. | Hou et al. (2018) | |
| Sprague–Dawley rats (E12.5 400 mg/kg i.p. injection | GABA-related proteins | GAD65 and GAD67 were decreased in cortical tissue. Increased high-frequency activity during wake and REM sleep | Cusmano and Mong, (2014) | |
| Wistar rats (VPA, 800 mg/kg b.w) | GABA neurotransmitter levels | Ex vivo HPLC studies Glutamate, Gln, and GABA significantly increased in male rat’s hippocampus. NMR studies showed increased levels of Gln and GABA in the VPA group | Zieminska et al. (2018) | |
| CD-1 strain or GFAP-eGFP transgenic mice (E12.5, 500 mg/kg i.p. injection | GABA receptor subunit expression pattern | GABAρ3 in PCs and EGCs from lobule X were reduced. GABAρ3 expression increases linearly throughout normal development of the cerebellum. GABAρ3 expression is disrupted in the VPA models | Varman et al. (2018) | |
| MIA models | C57BL/6 mice (E12.5 20 mg/kg of poly (I:C), i.p. injection | GABAergic neuron phenotype shift | Scn1a mRNA levels were not significantly changed; protein levels of NaV1.1 were decreased in the mPFC | Yang et al. (2021a) |
| C57BL/6 mice (E17 5 mg/kg intravenous (iv) | GABAergic neuron phenotype shift; GABA-related protein expression | Increase in the transcription of NKCC1 and decrease in KCC2. Reduced mRNA expression levels of GAD65, GAD67, and VGAT | Richetto et al. (2014) |
REM, rapid eye movement; EGCs, ependymal glial cells; PCs, Purkinje cells.