Abstract / Description of output
Introduction: The male and female offspring of rats exposed repeatedly to social stress in late pregnancy display enhanced hypothalamo-pituitary-adrenal (HPA) axis responses to stress in adulthood (Brunton and Russell, 2010; Brunton et al., 2015). We previously showed that deficits in 5α-reduced neurosteroid production in PNS offspring may contribute to HPA axis hyperactivity in a sex-dependent manner (Brunton et al., 2015), however concentrations of these neurosteroids in the brain were never directly measured.
Aims: Here, we aimed to establish whether neuroactive steroid concentrations in the brain were different between control and PNS rats, both basally and in response to an acute stressor (i.e. swim stress), which is known to result in a robust increase in neuroactive steroid concentrations in the brain (Sze et al., 2018).
Methods: Using liquid chromatography-mass spectrometry, we quantified a panel of nine neuroactive steroids: corticosterone; deoxycorticosterone (DOC), dihydrodeoxycorticosterone (DHDOC), THDOC; pregnenolone; progesterone; dihydroprogesterone, DHP; allopregnanolone; testosterone) in the plasma and in five brain regions under basal conditions and 30 minutes after the onset of 2 min period of forced swimming, in both male and female control and PNS rats.
Results and conclusions: Plasma corticosterone concentrations were not different between control and PNS rats. However, in the brain, the production of the GABAA allosteric positive modulator THDOC (but not allopregnanolone) seems to be compromised in both male and female PNS offspring following the acute stressor. We propose that compromises in stress-induced THDOC production may reflect deficits in neurosteroidogenic machinery in the brain and altered stress responses in PNS rats.
Aims: Here, we aimed to establish whether neuroactive steroid concentrations in the brain were different between control and PNS rats, both basally and in response to an acute stressor (i.e. swim stress), which is known to result in a robust increase in neuroactive steroid concentrations in the brain (Sze et al., 2018).
Methods: Using liquid chromatography-mass spectrometry, we quantified a panel of nine neuroactive steroids: corticosterone; deoxycorticosterone (DOC), dihydrodeoxycorticosterone (DHDOC), THDOC; pregnenolone; progesterone; dihydroprogesterone, DHP; allopregnanolone; testosterone) in the plasma and in five brain regions under basal conditions and 30 minutes after the onset of 2 min period of forced swimming, in both male and female control and PNS rats.
Results and conclusions: Plasma corticosterone concentrations were not different between control and PNS rats. However, in the brain, the production of the GABAA allosteric positive modulator THDOC (but not allopregnanolone) seems to be compromised in both male and female PNS offspring following the acute stressor. We propose that compromises in stress-induced THDOC production may reflect deficits in neurosteroidogenic machinery in the brain and altered stress responses in PNS rats.
Original language | English |
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Publication status | Unpublished - Jul 2020 |
Event | FENS 2020 Virtual Forum - Online Duration: 11 Jul 2020 → 15 Jul 2020 |
Conference
Conference | FENS 2020 Virtual Forum |
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Period | 11/07/20 → 15/07/20 |