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Maternal stress in pregnancy affects myelination and neurosteroid regulatory pathways in the guinea pig cerebellum.

  • Bennett, Greer A1, 2
  • Palliser, Hannah K1, 2
  • Shaw, Julia C1, 2
  • Palazzi, Kerrin L3
  • Walker, David W4
  • Hirst, Jonathan J1, 2
  • 1 a Mothers and Babies Research Centre , Hunter Medical Research Institute , Newcastle , New South Wales , Australia. , (Australia)
  • 2 b School of Biomedical Sciences and Pharmacy , University of Newcastle , New South Wales , Australia. , (Australia)
  • 3 c Clinical Research Design , Information Technology and Statistical Support (CReDITSS), Hunter Medical Research Institute (HMRI) , Newcastle , New South Wales , Australia. , (Australia)
  • 4 d School of Health and Biomedical Sciences , RMIT University , Bundoora , Victoria , Australia. , (Australia)
Published Article
Stress (Amsterdam, Netherlands)
Publication Date
Nov 01, 2017
DOI: 10.1080/10253890.2017.1378637
PMID: 28969480


Prenatal stress predisposes offspring to behavioral pathologies. These may be attributed to effects on cerebellar neurosteroids and GABAergic inhibitory signaling, which can be linked to hyperactivity disorders. The aims were to determine the effect of prenatal stress on markers of cerebellar development, a key enzyme in neurosteroid synthesis and the expression of GABAA receptor (GABAAR) subunits involved in neurosteroid signaling. We used a model of prenatal stress (strobe light exposure, 2 h on gestational day 50, 55, 60 and 65) in guinea pigs, in which we have characterized anxiety and neophobic behavioral outcomes. The cerebellum and plasma were collected from control and prenatally stressed offspring at term (control fetus: n = 9 male, n = 7 female; stressed fetus: n = 7 male, n = 8 female) and postnatal day (PND) 21 (control: n = 8 male, n = 8 female; stressed: n = 9 male, n = 6 female). We found that term female offspring exposed to prenatal stress showed decreased expression of mature oligodendrocytes (∼40% reduction) and these deficits improved to control levels by PND21. Reactive astrocyte expression was lower (∼40% reduction) following prenatal stress. GABAAR subunit (δ and α6) expression and circulating allopregnanolone concentrations were not affected by prenatal stress. Prenatal stress increased expression (∼150-250% increase) of 5α-reductase type-1 mRNA in the cerebellum, which may be a neuroprotective response to promote GABAergic inhibition and aid in repair. These observations indicate that prenatal stress exposure has marked effects on the development of the cerebellum. These findings suggest cerebellar changes after prenatal stress may contribute to adverse behavioral outcomes after exposure to these stresses.

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