title: GABAergic neurons in cerebellar interposed nucleus modulate cellular and humoral immunity via hypothalamic and sympathetic pathways.
abstract: Our previous work has shown that cerebellar interposed nucleus (IN) modulates immune function. Herein, we reveal mechanism underlying the immunomodulation. Treatment of bilateral cerebellar IN of rats with 3-mercaptopropionic acid (3-MP), a glutamic acid decarboxylase antagonist that reduces γ-aminobutyric acid (GABA) synthesis, enhanced cellular and humoral immune responses to bovine serum albumin, whereas injection of vigabatrin, a GABA-transaminase inhibitor that inhibits GABA degradation, in bilateral cerebellar IN attenuated the immune responses. The 3-MP or vigabatrin administrations in the cerebellar IN decreased or increased hypothalamic GABA content and lymphoid tissues' norepinephrine content, respectively, but did not alter adrenocortical or thyroid hormone levels in serum. In addition, a direct GABAergic projection from cerebellar IN to hypothalamus was found. These findings suggest that GABAergic neurons in cerebellar IN regulate immune system via hypothalamic and sympathetic pathways.
authors.affiliation: Department of Physiology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong, Jiangsu Province 226001, China.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Lu
authors.affiliation: Department of Physiology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong, Jiangsu Province 226001, China.
authors.forename: Xiao-Qin
authors.initials: XQ
authors.lastname: Wang
authors.affiliation: Department of Physiology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong, Jiangsu Province 226001, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Physiology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong, Jiangsu Province 226001, China. Electronic address: yhqiu@ntu.edu.cn.
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Qiu
authors.affiliation: Department of Physiology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong, Jiangsu Province 226001, China. Electronic address: yppeng@ntu.edu.cn.
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Peng
mesh_terms: D000305:Adrenal Cortex Hormones / Q000097:blood; D000818:Animals; D002417:Cattle; D002529:Cerebellar Nuclei / Q000187:drug effects / Q000276:immunology*; D018755:GABA Agonists / Q000494:pharmacology; D059330:GABAergic Neurons / Q000276:immunology*; D007031:Hypothalamus / Q000276:immunology* / Q000378:metabolism; D007111:Immunity, Cellular / Q000187:drug effects / Q000502:physiology*; D056724:Immunity, Humoral / Q000187:drug effects / Q000502:physiology*; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000235:genetics; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D008222:Lymphokines / Q000096:biosynthesis / Q000235:genetics; D009434:Neural Pathways / Q000502:physiology; D009638:Norepinephrine / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine / Q000276:immunology; D013564:Sympathetic Nervous System / Q000276:immunology*; D013963:Thyroid Hormones / Q000097:blood; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000305:Adrenal Cortex Hormones; D018755:GABA Agonists; D007075:Immunoglobulin M; D008222:Lymphokines; D012333:RNA, Messenger; D013963:Thyroid Hormones; D012710:Serum Albumin, Bovine; D005680:gamma-Aminobutyric Acid; D009638:Norepinephrine
keywords: Cellular immunity; Cerebellar interposed nucleus; Cerebellar-hypothalamic projection; GABA; Humoral immunity