Neuronal changes and cognitive deficits in a multi-hit rat model following cumulative impact of early life stressors.

Perinatal protein malnourishment (LP) is a leading cause for mental and physical retardation in children from poor socioeconomic conditions. Such malnourished children are vulnerable to additional stressors that may synergistically act to cause neurological disorders in adulthood. In this study, the above mentioned condition was mimicked via a multi-hit rat model in which pups born to LP mothers were co-injected with polyinosinic:polycytidylic acid (Poly I:C; viral mimetic) at postnatal day (PND) 3 and lipopolysaccharide (LPS; bacterial mimetic) at PND 9. Individual exposure of Poly I:C and LPS was also given to LP pups to correlate chronicity of stress. Similar treatments were also given to control pups. Hippocampal cellular apoptosis, β III tubulin catastrophe, altered neuronal profiling and spatial memory impairments were assessed at PND 180, using specific immunohistochemical markers (active caspase 3, β III tubulin, doublecortin), golgi studies and cognitive mazes (Morris water maze and T maze). Increase in cellular apoptosis, loss of dendritic arborization and spatial memory impairments were higher in the multi-hit group, than the single-hit groups. Such impairments observed due to multi-hit stress mimicked conditions similar to many neurological disorders and hence, it is hypothesized that later life neurological disorders might be an outcome of multiple early life hits.This article has an associated First Person interview with the first author of the paper.