10779/rcsi.10794257.v1
Lorna Farrelly
Lorna
Farrelly
Melanie Föcking
Melanie
Föcking
Yael Piontkewitz
Yael
Piontkewitz
Patrick Dicker
Patrick
Dicker
Jane A. English
Jane A.
English
Kieran Wynne
Kieran
Wynne
Mary Cannon
Mary
Cannon
Gerard Cagney
Gerard
Cagney
David R. Cotter
David R.
Cotter
Maternal immune activation induces changes in myelin and metabolic proteins, some of which can be prevented with risperidone in adolescence.
Royal College of Surgeons in Ireland
2019
Aging
Animals
Antipsychotic Agents
Disease Models
Animal
Female
Male
Myelin Sheath
Prefrontal Cortex
Pregnancy
Prenatal Exposure Delayed Effects
Rats
Wistar
Risperidone
Schizophrenia
Psychiatry (incl. Psychotherapy)
2019-11-22 17:08:35
Journal contribution
https://repository.rcsi.com/articles/journal_contribution/Maternal_immune_activation_induces_changes_in_myelin_and_metabolic_proteins_some_of_which_can_be_prevented_with_risperidone_in_adolescence_/10794257
<p><strong>BACKGROUND:</strong> Maternal infection is a risk factor for schizophrenia but the molecular and cellular mechanisms are not fully known. Myelin abnormalities are amongst the most robust neuropathological changes observed in schizophrenia, and preliminary evidence suggests that prenatal inflammation may play a role.</p>
<p><strong>METHODS:</strong> Label-free liquid chromatography-mass spectrometry was performed on the prefrontal cortex (PFC) of adult rat offspring born to dams that were exposed on gestational day 15 to the viral mimic polyinosinic:polycytidylic acid [poly(I:C), 4 mg/kg] or saline and treated with the atypical antipsychotic drug risperidone (0.045 mg/kg) or saline in adolescence. Western blotting was employed to validate protein changes.</p>
<p><strong>RESULTS:</strong> Over 1,000 proteins were quantified in the PFC with pathway analyses implicating changes in core metabolic pathways, following prenatal poly(I:C) exposure. Some of these protein changes were absent in the PFC of poly(I:C)-treated offspring that subsequently received risperidone treatment in adolescence. Particularly interesting reductions in the expression of the myelin-related proteins myelin basic protein isoform 3 (MBP1) and rhombex 29 were observed, which were reversed by risperidone treatment. Validation by Western blotting confirmed changes in MBP1 and mitogen-activated kinase 1 (MAPK1). Western blotting was extended to assess the MAPK signalling proteins due to their roles in inflammation, namely phosphorylated MAPK1 and phosphorylated MAPK-activated protein kinase 2. Both were upregulated by poly(I:C) treatment and reversed by risperidone treatment.</p>
<p><strong>CONCLUSIONS:</strong> Overall, our data suggest that maternal inflammation may contribute to an increased risk for schizophrenia through mechanisms involving metabolic function and myelin formation and that risperidone in adolescence may prevent or reverse such changes.</p>