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

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 GABA(A) receptor (GABA(A)R) subunits involved in neurosteroid signaling. We used a model of prenatal stress (strobe light exposure, 2h 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 (approximate to 40% reduction) and these deficits improved to control levels by PND21. Reactive astrocyte expression was lower (approximate to 40% reduction) following prenatal stress. GABA(A)R subunit ( and 6) expression and circulating allopregnanolone concentrations were not affected by prenatal stress. Prenatal stress increased expression (approximate to 150-250% increase) of 5-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.