Perinatal exposure to synergistic multiple stressors leads to cellular and behavioral deficits mimicking Schizophrenia-like pathology

Protein malnourishment and immune stress are potent perinatal stressors, encountered by children born under poor socioeconomic conditions. Thus, it is necessary to investigate how such stressors synergistically contribute towards developing neurological disorders in affected individuals. Pups from W...

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Bibliographic Details
Published in:Biology open 2022-03, Vol.11 (3)
Main Authors: Sarkar, Tiyasha, Patro, Nisha, Patro, Ishan Kumar
Format: Article
Language:English
Subjects:
Animals
Body Weight
Brain architecture
EGR-1 protein
Endotoxins
Exposure
Female
Gliosis
High protein diet
Hippocampus
Juveniles
lipopolysaccharide (lps)
Lipopolysaccharides
Lipopolysaccharides - adverse effects
Low protein diet
Mental disorders
multi-hit
Neurological diseases
Neurons
Nutrient deficiency
Perinatal exposure
Poly I
poly i:c
Polyinosinic:polycytidylic acid
Pregnancy
protein malnourishment
Proteins
Schizophrenia
Schizophrenia - diagnosis
Schizophrenia - etiology
Signs and symptoms
Socioeconomics
Spine
synaptic plasticity proteins
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Summary:Protein malnourishment and immune stress are potent perinatal stressors, encountered by children born under poor socioeconomic conditions. Thus, it is necessary to investigate how such stressors synergistically contribute towards developing neurological disorders in affected individuals. Pups from Wistar females, maintained on normal (high-protein, HP:20%) and low-protein (LP:8%) diets were used. Single and combined exposures of Poly I:C (viral mimetic: 5 mg/kg body weight) and Lipopolysaccharide (LPS; bacterial endotoxin: 0.3 mg/kg body weight) were injected to both HP and LP pups at postnatal days (PND) 3 and 9 respectively, creating eight groups: HP (control); HP+Poly I:C; HP+LPS; HP+Poly I:C+LPS; LP; LP+Poly I:C; LP+LPS; LP+Poly I:C+LPS (multi-hit). The effects of stressors on hippocampal cytoarchitecture and behavioral abilities were studied at PND 180. LP animals were found to be more vulnerable to immune stressors than HP animals and symptoms like neuronal damage, spine loss, downregulation of Egr 1 and Arc proteins, gliosis and behavioral deficits were maximum in the multi-hit group. Thus, from these findings it is outlined that cellular and behavioral changes that occur following multi-hit exposure may predispose individuals to developing Schizophrenia-like pathologies during adulthood.
ISSN:2046-6390
2046-6390
DOI:10.1242/bio.058870