Histamine regulation of microglia: Gene-environment interaction in the regulation of central nervous system inflammation.
Histamine regulation of microglia: Gene-environment interaction in the regulation of central nervous system inflammation.
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DOI：
10.1016/j.bbi.2016.07.002
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发表时间：
2016-10
影响因子：
15.1
通讯作者：
Pittenger, Christopher
中科院分区：
文献类型：
--
作者：
Frick, Luciana;Rapanelli, Maximiliano;Abbasi, Eeman;Ohtsu, Hiroshi;Pittenger, Christopher
小胶质细胞介导神经炎症并调节大脑发育和体内平衡。小胶质细胞异常与一系列神经精神病理学有关，包括抽动秽语综合症（TS）和自闭症。组胺 (HA) 既是一种神经递质，也是一种免疫调节剂。 HA 缺乏被认为是 TS 的罕见原因，并可能导致其他神经精神疾病。体外研究表明HA可以调节小胶质细胞，但这从未在体内进行过探索。我们使用免疫组织化学检查组氨酸脱羧酶 (Hdc) 敲除小鼠中 HA 缺乏的影响以及野生型动物中 HA 受体刺激的影响。我们发现 HA 通过 H4 受体调节体内小胶质细胞。 Hdc 敲除小鼠的慢性 HA 缺乏会减少纹状体和下丘脑（趋势水平）小胶质细胞的影响，但不会减少大脑其他部位的影响。下丘脑中组胺能神经元的耗竭也有类似的效果。表达 IGF-1 的小胶质细胞特别减少，然而，在 Hdc 敲除小鼠中，小胶质细胞对脂多糖 (LPS) 攻击的反应增强。组胺能信号的遗传异常可能会导致炎症挑战的脆弱性，从而为病理性神经免疫反应失调奠定基础。
Microglia mediate neuroinflammation and regulate brain development and homeostasis. Microglial abnormalities are implicated in a range of neuropsychiatric pathology, including Tourette syndrome (TS) and autism. Histamine (HA) is both a neurotransmitter and an immune modulator. HA deficiency has been implicated as a rare cause of TS and may contribute to other neuropsychiatric conditions. In vitro studies suggest that HA can regulate microglia, but this has never been explored in vivo. We used immunohistochemistry to examine the effects of HA deficiency in histidine decarboxylase (Hdc) knockout mice and of HA receptor stimulation in wild-type animals. We find HA to regulate microglia in vivo, via the H4 receptor. Chronic HA deficiency in Hdc knockout mice reduces ramifications of microglia in the striatum and (at trend level) in the hypothalamus, but not elsewhere in the brain. Depletion of histaminergic neurons in the hypothalamus has a similar effect. Microglia expressing IGF-1 are particularly reduced, However, the microglial response to challenge with lipopolysacchariade (LPS) is potentiated in Hdc knockout mice. Genetic abnormalities in histaminergic signaling may produce a vulnerability to inflammatory challenge, setting the state for pathogenically dysregulated neuroimmune responses.
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影响因子：
9.3
作者：
Ferreira R;Santos T;Gonçalves J;Baltazar G;Ferreira L;Agasse F;Bernardino L
通讯作者：
Bernardino L
组胺诱导组胺受体表达上调并增加小胶质细胞炎症介质的释放
影响因子：
5.1
作者：
Dong, Hongquan;Zhang, Wei;Zhang, Shu
通讯作者：
Zhang, Shu
影响因子：
4.8
作者：
Bloch M;State M;Pittenger C
通讯作者：
Pittenger C
影响因子：
4.2
作者：
Crain, Jessica M.;Nikodemova, Maria;Watters, Jyoti J.
通讯作者：
Watters, Jyoti J.
影响因子：
3.1
作者：
Ji K;Miyauchi J;Tsirka SE
通讯作者：
Tsirka SE