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

Abstract

Perinatal protein malnourishment is a leading cause for mental and physical retardation in children with poor socioeconomic conditions. Such malnourished children are vulnerable to additional stressors that may synergistically act to cause neurological disorders at adulthood. In this study, the above mentioned condition was mimicked via a multi-hit rat model in which pups born to protein malnourished mothers (LP) 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 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.

Multiple Early Life Stressors as Risk Factors for Neurodevelopmental Abnormalities in the F1 Wistar Rats

“…Clinical investigations have revealed how exposure to environmental stressors early in life and throughout the developmental years of childhood and adolescence results in resilient or maladaptive behavior with a significant impact on cognition later in life [5]. Multiple types of stressors (multi-hit), such as exposure to prenatal and postnatal malnutrition [6,7], viral and bacterial infections, trauma, and social maltreatment and neurotoxins [8,9] act in variable combinations and profoundly disrupt brain development, thus may considerably increase the pathophysiology of neuropsychiatric disorders in affected individuals. Moreover, maternal inflammatory reactions during pregnancy [10], antenatal infection in preterm newborns [11] and neonatal infection [12] have also been linked to a lower intelligence quotient in offspring and increased chances of developing neuropsychiatric disorders such as schizophrenia and depression [13].…”

First person – Tiyasha Sarkar

“… ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Biology Open, helping early-career researchers promote themselves alongside their papers. Tiyasha Sarkar is first author on ‘ Neuronal changes and cognitive deficits in a multi-hit rat model following cumulative impact of early life stressors ’, published in BiO. Tiyasha is a PhD scholar in the lab of Professor Ishan Kumar Patro at the School of Studies in Neuroscience, Jiwaji University Gwalior, Madhya Pradesh, India, investigating the correlation between multiple early life stressors and later life neurological disorders.…”