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Neuronal changes and cognitive deficits in a multi-hit rat model following cumulative impact of early life stressors
Tiyasha Sarkar1, Nisha Patro1, Ishan Kumar Patro2
1School of Studies in Neuroscience, Jiwaji University, Gwalior 474011, India.
Insights
Early life protein malnourishment combined with viral and bacterial stress significantly impairs cognitive function and neuronal development in rats. These findings suggest multiple early-life stressors may contribute to adult neurological disorders.
Area of Science:
- Neuroscience
- Developmental Biology
- Immunology
Background:
- Perinatal protein malnourishment (LP) is a significant risk factor for cognitive and physical deficits.
- Children with LP are susceptible to synergistic effects of additional stressors, potentially leading to adult neurological disorders.
Purpose of the Study:
- To investigate the long-term neurological consequences of combined early-life stressors in a rat model.
- To determine if multiple early-life insults exacerbate impairments compared to single insults.
Main Methods:
- A multi-hit rat model was developed using perinatal protein malnourishment, polyinosinic:polycytidylic acid (Poly I:C), and lipopolysaccharide (LPS).
- Assessments at postnatal day 180 included hippocampal apoptosis, β III tubulin, neuronal profiling, and spatial memory tests (Morris water maze, T maze).
Main Results:
- The multi-hit group exhibited significantly higher cellular apoptosis, dendritic arborization loss, and spatial memory deficits compared to single-hit groups.
- Both single and multi-hit exposures in malnourished pups showed increased impairments relative to controls.
Conclusions:
- Multiple early-life stressors, particularly in the context of perinatal malnourishment, can lead to persistent neurological impairments.
- This study supports the hypothesis that later-life neurological disorders may result from cumulative early-life stress exposures.
Abstract:
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.
