Rationale: Prenatal maternal immune activation (MIA) is an etiological risk factor for schizophrenia in offspring. Recently, parvalbumin (PV) positive interneuron deficits has been considered a critical pathology of many psych-cognitive disorders. Nevertheless, whether and how prenatal MIA affected PV interneuron in offspring remains largely unknown.
Objectives: Here, we aimed to assess the relationship between MIA with PV interneuron deficits in offspring, and explored the underling mechanisms.
Methods and results: Mouse model of MIA was induced using lipopolysaccharide (120 µg/kg) on gestational day 15-17. Open field, elevated plus maze, Y-Maze and novel object recognition tests were performed and local field potential was recorded on adult male offspring. PV interneuron, Translocator protein 18 kDa (TSPO), and BDNF/TrkB signaling were then evaluated. Using TPSO agonist and TrkB antagonist, the function of TSPO on PV interneuron deficits was elucidated. Our results showed that MIA induced cognitive symptoms in the adult male offspring, accompanied by down-regulated PV and TSPO expression as well as decreased theta oscillation. Notably, activating TSPO reversed MIA-induced PV interneuron defects and behavioral abnormalities. Furthermore, specific inhibition of BDNF/TrkB signaling intercepted the protective effect of TSPO activation on PV interneuron deficits.
Conclusions: Our results highlight TSPO activation might prevented PV interneuron deficits and behavioral abnormalities after MIA via BDNF/TrkB signaling.
Keywords: BDNF/TrkB signaling; Cognitive impairment; Maternal immune activation; Parvalbumin interneuron; Schizophrenia; Translocator protein (TSPO).
© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.