Epigenetic Regulation of Adult Hippocampal Neurogenesis in a Childhood Stress Model Relevant to Internally Displaced Children in North East Nigeria

Early life adversity, including displacement, food insecurity, and psychosocial trauma, has profound effects on adult hippocampal neurogenesis with lasting consequences for memory, stress regulation, and mood. The millions of internally displaced children in North East Nigeria represent a population at high risk of these neurobiological sequelae. Epigenetic mechanisms, including DNA methylation and histone modification at neurogenesis-related gene loci, are increasingly recognised as mediators of early adversity-neurogenesis interactions. This study aims to characterise the epigenetic regulation of adult hippocampal neurogenesis in a validated early life chronic unpredictable stress model, with a focus on the promoter methylation of brain-derived neurotrophic factor, cyclic AMP response element-binding protein, and doublecortin genes. Sixty Wistar rat pups will be subjected to maternal separation and early stress protocols from postnatal days 2 to 21. At adulthood, hippocampal neurogenesis will be assessed by 5-bromo-2-deoxyuridine labelling combined with doublecortin immunofluorescence and unbiased stereological counting. Methylation patterns at target loci will be assessed by methylation-specific PCR and bisulfite sequencing. Cognitive function will be evaluated by Morris water maze and contextual fear conditioning. This study will generate an original epigenetic neuroanatomical framework for understanding hippocampal plasticity following early life adversity, directly applicable to the neurorehabilitation needs of displaced children in conflict-affected North East Nigeria.

Keywords: hippocampal neurogenesis, epigenetics, early life stress, displacement, North East Nigeria