Coplan Jeremy D, Gupta Nishant K, Flynn Sarah K, Reiner Wade J, Gaita David, Fulton Sasha L, Rozenboym Anna V, Tang Jean E, Cooper Thomas B, Mann J John
Department of Psychiatry and Behavioral Sciences, State University of New York Downstate Medical Center, Brooklyn, NY, USA.
College of Medicine, State University of New York Downstate Medical Center, Brooklyn, NY, USA.
Chronic Stress (Thousand Oaks). 2018 Jan-Dec;2. doi: 10.1177/2470547018785625. Epub 2018 Jul 6.
Maternal response to allostatic overload during infant rearing may alter neurobiological measures in grown offspring, potentially increasing susceptibility to mood and anxiety disorders. We examined maternal cerebrospinal fluid (CSF) glutamate response during exposure to variable foraging demand (VFD), a bonnet macaque model of allostatic overload, testing whether activation relative to baseline predicted concomitant CSF elevations of the stress neuropeptide, corticotropin-releasing factor. We investigated whether VFD-induced activation of maternal CSF glutamate affects maternal-infant attachment patterns and offspring CSF 5-hydroxyindoleacetic acid concentrations.
Mother-infant dyads were exposed to the "VFD stressor," a paradigm in which mothers experience 16 weeks of foraging uncertainty while rearing their infant offspring. Through staggering the infant age of VFD onset, both a cross-sectional design and a longitudinal design were used. Maternal CSF glutamate and glutamine concentrations post-VFD exposure were cross-sectionally compared to maternal VFD naive controls. Proportional change in concentrations of maternal glutamate (and glutamine), a longitudinal measure, was evaluated in relation to VFD-induced elevations of CSF corticotropin-releasing factor. The former measure was related to maternal-infant proximity scores obtained during the final phases of VFD exposure. Maternal glutamatergic response to VFD exposure was used as a predictor variable for young adolescent offspring CSF metabolites of serotonin, dopamine, and norepinephrine.
Following VFD exposure, maternal CSF glutamate concentrations correlated positively with maternal CSF CRF concentrations. Activation relative to baseline of maternal CSF glutamate concentrations following VFD exposure correlated directly with a) increased maternal-infant proximity during the final phases of VFD and b) offspring CSF concentrations of monoamine metabolites including 5-hydroxyindoleacetic acid, which was elevated relative to controls.
Activation of maternal CSF glutamate in response to VFD-induced allostasis is directly associated with elevations of maternal CSF corticotropin-releasing factor. Maternal CSF glutamate alterations induced by VFD potentially compromise serotonin neurotransmission in grown offspring, conceivably modeling human vulnerability to treatment-resistant mood and anxiety disorders.
母亲在抚养婴儿期间对稳态负荷过载的反应可能会改变成年后代的神经生物学指标，从而可能增加其患情绪和焦虑障碍的易感性。我们研究了在可变觅食需求（VFD）暴露期间母亲脑脊液（CSF）谷氨酸的反应，VFD是一种稳态负荷过载的帽猴模型，测试相对于基线的激活是否能预测应激神经肽促肾上腺皮质激素释放因子（CRF）在脑脊液中的相应升高。我们调查了VFD诱导的母亲脑脊液谷氨酸激活是否会影响母婴依恋模式以及后代脑脊液5-羟吲哚乙酸的浓度。
母婴二元组暴露于“VFD应激源”，即母亲在抚养婴儿后代时经历16周觅食不确定性的范式。通过错开VFD开始时婴儿的年龄，采用了横断面设计和纵向设计。VFD暴露后母亲脑脊液谷氨酸和谷氨酰胺浓度与未接触VFD的母亲对照组进行横断面比较。纵向测量母亲谷氨酸（和谷氨酰胺）浓度的比例变化，以评估其与VFD诱导的脑脊液促肾上腺皮质激素释放因子升高的关系。前一项测量与VFD暴露最后阶段获得的母婴接近度分数相关。母亲对VFD暴露的谷氨酸能反应被用作年轻青少年后代脑脊液中血清素、多巴胺和去甲肾上腺素代谢物的预测变量。
VFD暴露后，母亲脑脊液谷氨酸浓度与母亲脑脊液CRF浓度呈正相关。VFD暴露后母亲脑脊液谷氨酸浓度相对于基线的激活与以下因素直接相关：a）VFD最后阶段母婴接近度增加；b）后代脑脊液中包括5-羟吲哚乙酸在内的单胺代谢物浓度相对于对照组升高。
母亲脑脊液谷氨酸对VFD诱导的稳态变化的激活与母亲脑脊液促肾上腺皮质激素释放因子的升高直接相关。VFD诱导的母亲脑脊液谷氨酸变化可能会损害成年后代的血清素神经传递，这可能模拟了人类对难治性情绪和焦虑障碍的易感性。
