Effects of Neonatal Lipopolysaccharide Injections at Various Developmental Stages on Long-term Behavioral Outcomes, Oxidative Stress, and Brain Histology in Rats

El Marzouki, Zineb; Mallouk, Hasnaa; Lamtai, Mouloud; Dimaoui, Amal; Ouanouche, El Hassan; Lakhlifi, Jihane; Mesfioui, Abdelhalem; El Hessni, Aboubaker

doi:10.21608/javs.2025.373050.1577

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	Effects of Neonatal Lipopolysaccharide Injections at Various Developmental Stages on Long-term Behavioral Outcomes, Oxidative Stress, and Brain Histology in Rats
Article 6, Volume 10, Issue 3, July 2025, Page 48-61 PDF (542.19 K)
Document Type: Original Article
DOI: 10.21608/javs.2025.373050.1577
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Authors
Zineb El Marzouki ¹; Hasnaa Mallouk ¹; Mouloud Lamtai ²; Amal Dimaoui ¹; El hassan Ouanouche³; Jihane Lakhlifi²; Abdelhalem Mesfioui¹; Aboubaker El Hessni¹
¹Laboratory of Biology and Health, Department of Biology, Faculty of Sciences, Ibn Tofail University, Kenitra, Morocco
²Laboratory of Biology and Health, Department of Biology, Faculty of Sciences, Ibn Tofail University, Kenitra, Morocco.
³Laboratory of Biology and Health, Department of Biology, Faculty of Sciences, Ibn Tofail University, Kenitra, Morocco Higher Institute of Nursing and Health Technology of Tanger. Morocco
Receive Date: 06 April 2025, Revise Date: 12 May 2025, Accept Date: 15 May 2025
Abstract
The developing nervous system is highly susceptible to adverse events, particularly during critical periods. Disruptions, such as neonatal infections, can significantly alter brain structure and function, potentially contributing to the development of affective disorder-like behavior. In this study, we examined the effects of early lipopolysaccharide (LPS) exposure at two distinct postnatal days (PND). On PND 9 and 21, male and female rats were divided into two groups: one received intraperitoneal LPS injections at 0.2 mg/kg body weight, while the control group received intraperitoneal saline injections on the same days. Each group consisted of 5 rats per sex, resulting in 10 animals per group. After two months, both groups underwent a series of behavioral tests, oxidative stress assessments, and histological analyses. Myelination was evaluated using Luxol Fast Blue staining, while neuronal morphology and count were assessed using Cresyl Violet staining. The results revealed a reduction in the number of cells in the prefrontal cortex (PFC) and hippocampus (HPC), along with demyelination in the corpus callosum. These neuroanatomical changes were associated with depressive behaviors and memory impairments in both sexes, with a more pronounced effect in males. Furthermore, elevated oxidative stress levels were observed marked by significant increases in nitric oxide and lipid peroxidation markers in males. Sex differences were evident across the majority of measured outcomes. These findings highlight the critical role of early immune challenges in brain development and their potential contribution to neuropsychiatric disorders later in life.
Keywords
Critical period; Lipopolysaccharide; Neurodevelopmental disorders; Rat; Sexual dimorphism
Main Subjects
Physiology


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