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Prenatal stress-related alterations in synaptic transmission and 5-HT7 receptor-mediated effects in the rat dorsal raphe nucleus are ameliorated by the 5-HT7 receptor antagonist SB 269970.
European Journal of Neuroscience ( IF 2.7 ) Pub Date : 2020-05-13 , DOI: 10.1111/ejn.14778 Joanna Sowa 1 , Grzegorz Hess 1
European Journal of Neuroscience ( IF 2.7 ) Pub Date : 2020-05-13 , DOI: 10.1111/ejn.14778 Joanna Sowa 1 , Grzegorz Hess 1
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Early life adversity exerts a detrimental influence on developing brain neuronal networks and its consequences may include mental health disorders. In rats, prenatal stress may lead to anxiety and depressive‐like behavior in the offspring. Several lines of evidence implicated an involvement of prenatal stress in alterations of the brain serotonergic system functions, but the effects of prenatal stress on its core, the dorsal raphe nucleus (DRN), still remain incompletely understood. The present study was aimed at finding whether prenatal stress induces modifications in the glutamatergic and GABAergic inputs to DRN projection cells and whether it affects DRN 5‐HT7 receptors, which modulate activity of these synapses. Prenatal stress resulted in an increase in basal frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and in a decrease in basal frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) recorded from putative projection neurons in DRN slices ex vivo. While there were no changes in the excitability of DRN projection neurons, the 5‐HT7 receptor‐mediated reduction in the sEPSC frequency and rise in the sIPSC frequency, seen in control rats, were largely absent in slices obtained from prenatally stressed rats. Repeated administration of SB 269970, a 5‐HT7 receptor antagonist, resulted in a reversal of prenatal stress‐induced alterations in 5‐HT7 receptor‐mediated effects on the sEPSC/sIPSC frequency. Moreover, the treatment reversed prenatal stress‐induced alterations in basal excitatory transmission and partially reversed the effect of stress on basal inhibitory transmission in the DRN.
中文翻译：
5-HT7受体拮抗剂SB 269970改善了大鼠背沟核中与产前应激相关的突触传递变化和5-HT7受体介导的作用。
早期生活逆境对发展中的大脑神经元网络产生不利影响，其后果可能包括心理健康障碍。在大鼠中，产前压力可能导致后代焦虑和抑郁样行为。有几条证据表明，产前压力与脑血清素能系统功能的改变有关，但是，产前压力对其核心，背缝核（DRN）的影响仍不完全清楚。本研究旨在发现产前应激是否诱导DRN投射细胞的谷氨酸能和GABA能输入改变，以及是否影响DRN 5-HT 7。受体，调节这些突触的活性。产前应激导致DRN切片中离体的推定投射神经元记录的自发性兴奋性突触后突触电流（sEPSCs）的基础频率的增加和自发性抑制性突触后突触电流（sIPSCs）的基础频率的降低。虽然DRN投射神经元的兴奋性没有变化，但在对照组大鼠中，从产前应激大鼠获得的切片中却基本上没有5-HT 7受体介导的sEPSC频率降低和sIPSC频率升高。重复施用5‐HT 7受体拮抗剂SB 269970，可逆转产前应激引起的5‐HT 7改变受体介导的对sEPSC / sIPSC频率的影响。此外，该疗法逆转了产前应激诱导的基础兴奋性传递的改变，并部分逆转了压力对DRN中基础抑制传递的影响。
更新日期：2020-05-13
中文翻译：
5-HT7受体拮抗剂SB 269970改善了大鼠背沟核中与产前应激相关的突触传递变化和5-HT7受体介导的作用。
早期生活逆境对发展中的大脑神经元网络产生不利影响，其后果可能包括心理健康障碍。在大鼠中，产前压力可能导致后代焦虑和抑郁样行为。有几条证据表明，产前压力与脑血清素能系统功能的改变有关，但是，产前压力对其核心，背缝核（DRN）的影响仍不完全清楚。本研究旨在发现产前应激是否诱导DRN投射细胞的谷氨酸能和GABA能输入改变，以及是否影响DRN 5-HT 7。受体，调节这些突触的活性。产前应激导致DRN切片中离体的推定投射神经元记录的自发性兴奋性突触后突触电流（sEPSCs）的基础频率的增加和自发性抑制性突触后突触电流（sIPSCs）的基础频率的降低。虽然DRN投射神经元的兴奋性没有变化，但在对照组大鼠中，从产前应激大鼠获得的切片中却基本上没有5-HT 7受体介导的sEPSC频率降低和sIPSC频率升高。重复施用5‐HT 7受体拮抗剂SB 269970，可逆转产前应激引起的5‐HT 7改变受体介导的对sEPSC / sIPSC频率的影响。此外，该疗法逆转了产前应激诱导的基础兴奋性传递的改变，并部分逆转了压力对DRN中基础抑制传递的影响。
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