Stepanichev Mikhail Yu, Goryakina Tatyana, Manolova Anna, Lazareva Natalia, Kvichanskii Alexey, Tretyakova Liya, Volobueva Maria, Gulyaeva Natalia
Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow, Russia.
Laboratory of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Butlerova Street, 5A, Moscow, 117485, Russia.
Brain Struct Funct. 2021 Mar;226(2):563-574. doi: 10.1007/s00429-020-02199-z. Epub 2021 Jan 5.
Neonatal proinflammatory challenge (NPC) may contribute to the development of psychiatric disorders in adults. A double exposure of neonatal rats to lipopolysaccharide, a component of cellular wall of gram-negative bacteria, on postnatal days 3 and 5 provokes the development of depressive- and anxiety-like behaviors. NPC impairs neuroplasticity and cognition in adult animals, significant modifications of neuroplasticity being evident even in adolescence. We studied effects of NPC on microglia and GABAergic neuronal population of the dorsal hippocampus in juvenile male and female rats using immunofluorescent histochemistry. The expression of glutamic acid decarboxylase-67 (GAD67) and calcium-binding proteins calretinin, calbindin, and parvalbumin were used as quantitative markers of GABAergic interneurons and their specific subpopulations, respectively. NPC induced changes of microglial morphology indicating inflammatory activation mostly expressed in CA3 field; the effect was similar in males and females. The number of GAD67 expressing neurons was similar in the dorsal hippocampus of females and males independently on the NPC. The portion of calbindin-immunoreactive GAD67-positive neurons significantly increased while the portion of calretinin-immunoreactive GAD67-positive neurons significantly decreased in the CA1 field of rats exposed to NPC independently on their sex. NPC did not affect the parvalbumin-positive subpopulation of GABAergic neurons in the hippocampus of rats of either sex. These data suggest that NPC-induced modification of GABAergic neuronal population composition under the proinflammatory conditions is involved in the maintenance of excitation/inhibition homeostatic balance in the hippocampus.
新生儿促炎刺激（NPC）可能导致成年人精神疾病的发生。在出生后第3天和第5天，给新生大鼠两次注射脂多糖（革兰氏阴性菌细胞壁的一种成分），会引发抑郁样和焦虑样行为。NPC会损害成年动物的神经可塑性和认知能力，即使在青春期，神经可塑性也会有明显改变。我们使用免疫荧光组织化学方法，研究了NPC对幼年雄性和雌性大鼠背侧海马区小胶质细胞和GABA能神经元群体的影响。分别使用谷氨酸脱羧酶-67（GAD67）的表达以及钙结合蛋白钙视网膜蛋白、钙结合蛋白和小白蛋白作为GABA能中间神经元及其特定亚群的定量标志物。NPC诱导小胶质细胞形态改变，表明炎症激活主要表现在CA3区；雄性和雌性的效果相似。无论是否存在NPC刺激，雌性和雄性大鼠背侧海马区中表达GAD67的神经元数量相似。在暴露于NPC的大鼠CA1区，无论性别如何，钙结合蛋白免疫反应性GAD67阳性神经元的比例显著增加，而钙视网膜蛋白免疫反应性GAD67阳性神经元的比例显著降低。NPC对两性大鼠海马区GABA能神经元的小白蛋白阳性亚群没有影响。这些数据表明，在促炎条件下，NPC诱导的GABA能神经元群体组成改变参与了海马体中兴奋/抑制稳态平衡的维持。
