Type

Journal Article

Authors

David R Cotter
Gerard Cagney
Mary Cannon
Kieran Wynne
Jane English
Patrick Dicker
Yael Piontkewitz
Melanie Föcking
Lorna Farrelly

Subjects

Biochemistry

Topics
myelin proteins mapk signalling prefrontal cortex pfc poly i c maternal infection liquid chromatography mass spectrometry protein kinase risk factor

Maternal immune activation induces changes in myelin and metabolic proteins, some of which can be prevented with risperidone in adolescence. (2014)

Abstract 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. 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. 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. 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.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

David R Cotter, Gerard Cagney, Mary Cannon, Kieran Wynne, Jane English, Patrick Dicker, Yael Piontkewitz, Melanie Föcking, Lorna Farrelly

Experts in our system

1
David R Cotter
Royal College of Surgeons in Ireland
Total Publications: 56
 
2
Gerard Cagney
Royal College of Surgeons in Ireland
Total Publications: 54
 
3
Mary Cannon
Royal College of Surgeons in Ireland
Total Publications: 90
 
4
Kieran Wynne
Royal College of Surgeons in Ireland
Total Publications: 45
 
5
Jane A English
Royal College of Surgeons in Ireland
Total Publications: 24
 
6
Patrick Dicker
Royal College of Surgeons in Ireland
Total Publications: 95
 
7
Melanie Föcking
Royal College of Surgeons in Ireland
Total Publications: 20
 
8
Lorna Farrelly
Royal College of Surgeons in Ireland
Total Publications: 4