Early-Life Immune Activation by Lipopolysaccharides and Its Impact on Cognitive and Negative Signs in a Schizophrenia Rat Model
Early-Life Immune Activation by Lipopolysaccharides and Its Impact on Cognitive and Negative Signs in a Schizophrenia Rat Model
Zineb El Marzouki1*, Laila Ibouzine-Dine1, Mouloud Lamtai1, El Hassan Ouanouche1,2, Abdelhalem Mesfioui1, Aboubaker El Hessni1
ABSTRACT
Disruption of central nervous system development during critical periods, particularly due to adverse events like early infections, can profoundly impact brain structure and function. These disturbances may contribute to the onset of adult neuropsychiatric disorders, including schizophrenia. In this study, we focused on the critical phases of postnatal brain development, evaluating the long-term effects of repeated early postnatal exposure to lipopolysaccharides (LPS), a bacterial endotoxin, on cognitive and negative symptoms associated with schizophrenia in male and female Wistar rats. The rats were randomized into two groups: the group that received intraperitoneal injections (IP) of LPS on postnatal days (PND) 0, 4, 9, and 14 and the control group that received IP injections of saline on the same PND. After two months, the rats were subjected to neurobehavioral assessment, biochemical and histological analysis. The behavioral consequences studied following exposure to LPS early in life reflect the cognitive and negative signs of schizophrenia. Rats subjected to repeated LPS administration showed increased anxiety and depression, reduced social interaction, and cognitive decline in comparison with control groups. This difference was significantly greater in females than in males. In addition, groups receiving LPS treatment also showed significantly higher levels of oxidative stress in the prefrontal cortex and a reduction in the number of neurons in the CA3 region of the hippocampus (HPC). Overall, these findings demonstrate that repeated postnatal administration of LPS may result in the cognitive and negative impairments of schizophrenia, highlighting the sex-dependent nature of the effects of LPS.
Keywords | Lipopolysaccharide, Schizophrenia, Hippocampus, Mammalian brain, Oxidative stress, Sexual dimorphism
To share on other social networks, click on any share button. What are these?
June 2025
Adv. Anim. Vet. Sci., Vol. 13, Iss. 6,
