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Perinatal exposure to synergistic multiple stressors leads to cellular and behavioral deficits mimicking

Tiyasha Sarkar1, Nisha Patro1, Ishan Kumar Patro1

  • 1School of Studies in Neuroscience, Jiwaji University, Gwalior 474011, India.

Biology Open
|February 2, 2022
PubMed

Insights

Protein malnourishment combined with immune stress during development can lead to neurological issues. This study shows "multi-hit" exposure in early life may predispose individuals to schizophrenia-like conditions later in life.

Area of Science:

  • Neuroscience
  • Immunology
  • Developmental Biology

Background:

  • Perinatal protein malnourishment and immune challenges are significant stressors for infants from disadvantaged backgrounds.
  • These stressors can synergistically impact neurological development, potentially leading to long-term disorders.

Purpose of the Study:

  • To investigate the combined effects of protein malnourishment and immune stressors (Poly I:C and LPS) on hippocampal development and behavior.
  • To determine if these synergistic stressors predispose offspring to schizophrenia-like pathologies.

Main Methods:

  • Wistar rat pups were fed either a normal (high-protein, HP) or low-protein (LP) diet.
  • Pups received single or combined injections of Poly I:C (viral mimetic) and LPS (bacterial endotoxin) at postnatal days 3 and 9.
  • Hippocampal cytoarchitecture and behavioral abilities were assessed at postnatal day 180.

Main Results:

  • Low-protein (LP) animals exhibited increased vulnerability to immune stressors compared to high-protein (HP) animals.
  • The 'multi-hit' group (LP + Poly I:C + LPS) showed maximum neuronal damage, spine loss, protein downregulation (Egr 1, Arc), gliosis, and behavioral deficits.
  • These cellular and behavioral changes suggest a predisposition to schizophrenia-like pathologies.

Conclusions:

  • Combined perinatal protein malnourishment and immune stress create a 'multi-hit' scenario with lasting detrimental effects on brain development.
  • This 'multi-hit' exposure model may serve as a valuable tool for understanding the developmental origins of schizophrenia-like pathologies.

Keywords:
Lipopolysaccharide (LPS)Multi-hitPoly I:CProtein malnourishmentSchizophreniaSynaptic plasticity proteins

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