title: Cerebellar fastigial nuclear GABAergic projections to the hypothalamus modulate immune function.
abstract: Our previous work has shown that the cerebellar fastigial nucleus (FN) is involved in modulation of lymphocyte function. Herein, we investigated effect of FN γ-aminobutyric acid (GABA)-ergic projections to the hypothalamus on lymphocytes to understand pathways and mechanisms underlying cerebellar immunomodulation. By injection of Texas red dextran amine (TRDA), an anterograde tracer, into FN, we found that the TRDA-labeled fibers from the FN traveled through the superior cerebellar peduncle (SCP), crossed in decussation of SCP (XSCP), entered the hypothalamus, and primarily terminated in the lateral hypothalamic area (LHA). Further, by injecting Fluoro-Ruby (FR), a retrograde tracer, in LHA, we observed that the FR-stained fibers retrogradely passed through XSCP and reached FN. Among these FR-positive neurons in the FN, there were GABA-immunoreactive cells. We then microinjected vigabatrin, which is an inhibitor of GABA-transaminase (GABA-T) that degrades GABA, bilaterally into FN. The vigabatrin treatment increased both number of GABA-immunoreactive neurons in FN-LHA projections and GABA content in the hypothalamus. Simultaneously, vigabatrin significantly reduced concanavalin A (Con A)-induced lymphocyte proliferation, anti-sheep red blood cell (SRBC) IgM antibody level, and natural killer (NK) cell number and cytotoxicity. In support of these findings, we inhibited GABA synthesis by using 3-mercaptopropionic acid (3-MP), which antagonizes glutamic acid decarboxylase (GAD). We found that the inhibition of GABA synthesis caused changes that were opposite to those when GABA was increased with vigabatrin. These findings show that the cerebellar FN has a direct GABAergic projection to the hypothalamus and that this projection actively participates in modulation of lymphocytes.
authors.affiliation: Department of Physiology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, China.
authors.forename: Bei-Bei
authors.initials: BB
authors.lastname: Cao
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Lu
authors.forename: Fen-Fen
authors.initials: FF
authors.lastname: Xu
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Qiu
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Peng
mesh_terms: D015097:3-Mercaptopropionic Acid / Q000494:pharmacology; D000818:Animals; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D002529:Cerebellar Nuclei / Q000187:drug effects / Q000276:immunology*; D002851:Chromatography, High Pressure Liquid; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D003911:Dextrans; D005456:Fluorescent Dyes; D018682:GABA Agents / Q000494:pharmacology; D059330:GABAergic Neurons / Q000187:drug effects / Q000276:immunology*; D005968:Glutamate Decarboxylase / Q000037:antagonists & inhibitors; D007031:Hypothalamus / Q000187:drug effects / Q000276:immunology*; D007075:Immunoglobulin M / Q000187:drug effects / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D009412:Nerve Fibers / Q000187:drug effects / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012235:Rhodamines; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D020888:Vigabatrin / Q000494:pharmacology; D014966:Xanthenes
chemical_list: D003911:Dextrans; D005456:Fluorescent Dyes; C067661:Fluoro-Ruby; D018682:GABA Agents; D007075:Immunoglobulin M; D012235:Rhodamines; D014966:Xanthenes; C034657:Texas red; D015097:3-Mercaptopropionic Acid; D005968:Glutamate Decarboxylase; D020888:Vigabatrin