GABAergic and inflammatory changes in the frontal cortex following neonatal PCP plus isolation rearing, as a dual-hit neurodevelopmental model for schizophrenia.
Molecular neurobiology September 1, 2024 Jennifer A Cale, Ethan J Chauhan, Joshua J Cleaver et al. 8 citations
Rats exposed to both neonatal PCP and post-weaning isolation (dual-hit) showed reduced parvalbumin, a marker of GABAergic interneurons, in multiple frontal cortical regions, while isolation-only rats showed reductions only in prelimbic/infralimbic cortex. The dual-hit rats also had increased microglial activation in medial/ventral orbitofrontal cortex and elevated IL-6 in frontal cortex, changes not seen with isolation alone. These neurochemical deficits—involving GABA and inflammation—parallel those in schizophrenia, supporting the dual-hit model's use for testing therapies targeting excitatory-inhibitory imbalance or neuroinflammation.