Prenatal immune activation and adult Poly(I:C) re-challenge promote neuroimmune priming and AD-related behavioural, cellular and molecular alterations in wild-type mice - Summary - MDSpire
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Prenatal immune activation and adult Poly(I:C) re-challenge promote neuroimmune priming and AD-related behavioural, cellular and molecular alterations in wild-type mice
To investigate whether prenatal immune stimulation followed by adult systemic re-challenge with Poly(I:C) induces persistent cognitive, motivational, and social deficits, as well as hippocampal neurodegeneration in wild-type mice.
Approach:
Study Design: Pregnant C57Bl/6J dams received Poly(I:C) at gestational day 17; male offspring received Poly(I:C) at 9 months. Behavioral assessments included recognition memory, working memory, reward-related learning, and social interaction, followed by hippocampal analysis at 12 months.
Key Findings:
Poly(I:C)-exposed mice exhibited impaired recognition and working memory.
Reduced palatable food-induced conditioned place preference and blunted social investigation were observed.
Increased amyloidogenic APP processing and tau dysregulation were noted in the hippocampus.
Microglial activation and synaptic alterations were present, alongside bioenergetic impairment.
Interpretation:
Repeated prenatal and postnatal peripheral activation of innate immunity may contribute to neurodegenerative phenotypes relevant to Alzheimer's disease susceptibility.
Conclusion:
The findings suggest that immune activation could play a role in the development of Alzheimer's disease-related changes.
