Quetiapine Ameliorates MIA-Induced Impairment of Sensorimotor Gating: Focus on Neuron-Microglia Communication and the Inflammatory Response in the Frontal Cortex of Adult Offspring of Wistar Rats

• Published in: Cells (Basel, Switzerland) Vol. 11; no. 18; p. 2788
• Main Authors: Chamera, Katarzyna, Curzytek, Katarzyna, Kamińska, Kinga, Trojan, Ewa, Basta-Kaim, Agnieszka
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.09.2022; MDPI
• Subjects: Animal cognition; Animal models; Antipsychotics; Aripiprazole; CD200 antigen; Cell interaction; Channel gating; Chlorpromazine; Cortex (frontal); CX3CR1 protein; Dosage and administration; Health aspects; Hippocampus; Histamine; Immune response; Inflammation; Laboratory animals; Lipopolysaccharides; maternal immune activation; Mental disorders; Microglia; Neuronal-glial interactions; Neurons; neuron–microglia axes; Offspring; Perceptual-motor processes; Prefrontal cortex; Psychotropic drugs; Quetiapine; Schizophrenia; Sensorimotor gating; Vagina; Poland; St Louis Missouri; United States > US
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells11182788

The maternal immune activation produced by the systemic administration of lipopolysaccharide (LPS) in rats provides valuable insights into the basis of behavioural schizophrenia-like disturbances and biochemical changes in the brains of the offspring, such as microglial activation. Regarding therapy, antipsychotics continually constitute the cornerstone of schizophrenia treatment. To their various efficacy and side effects, as well as not fully recognised mechanisms of action, further characteristics have been suggested, including an anti-inflammatory action via the impact on neuron–microglia axes responsible for inhibition of microglial activation. Therefore, in the present study, we sought to determine whether chronic treatment with chlorpromazine, quetiapine or aripiprazole could influence schizophrenia-like behavioural disturbances at the level of sensorimotor gating in male offspring prenatally exposed to LPS. Simultaneously, we wanted to explore if the chosen antipsychotics display a positive impact on the neuroimmunological parameters in the brains of these adult animals with a special focus on the ligand-receptor axes controlling neuron–microglia communication as well as pro- and anti-inflammatory factors related to the microglial activity. The results of our research revealed the beneficial effect of quetiapine on deficits in sensorimotor gating observed in prenatally LPS-exposed offspring. In terms of axes controlling neuron–microglia communication and markers of microglial reactivity, we observed a subtle impact of quetiapine on hippocampal Cx3cl1 and Cx3cr1 levels, as well as cortical Cd68 expression. Hence, further research is required to fully define and explain the involvement of quetiapine and other antipsychotics in Cx3cl1-Cx3cr1 and/or Cd200-Cd200r axes modulation and inflammatory processes in the LPS-based model of schizophrenia-like disturbances.