TY - JOUR
T1 - Histamine regulation of microglia
T2 - Gene-environment interaction in the regulation of central nervous system inflammation
AU - Frick, Luciana
AU - Rapanelli, Maximiliano
AU - Abbasi, Eeman
AU - Ohtsu, Hiroshi
AU - Pittenger, Christopher
N1 - Funding Information:
We gratefully acknowledge Stacey Wilber and Jessica André for assistance with mouse care and genotyping and Eric Wohleb and Ania Majewska for constructive discussions and comments on the manuscript. This work was supported by the Allison Family Foundation (CP), the Tourette Syndrome Association (LF), the Massachusetts General Hospital Research Fund (CP), and the State of Connecticut through its support of the Ribicoff Research Facilities at the Connecticut Mental Health Center .
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/10/1
Y1 - 2016/10/1
N2 - 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.
AB - 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.
KW - Basal ganglia
KW - H4R receptor
KW - IGF-1
KW - Lipopolysaccharide
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U2 - 10.1016/j.bbi.2016.07.002
DO - 10.1016/j.bbi.2016.07.002
M3 - Article
AN - SCOPUS:84992187650
VL - 57
SP - 326
EP - 337
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
SN - 0889-1591
ER -