title: Role of cerebellohypothalamic GABAergic projection in mediating cerebellar immunomodulation.
abstract: Our previous studies have shown that the cerebellar interposed nucleus (IN) modulates lymphocyte functions. As the cerebellum does not have a direct contact with the immune system, it is required to explore the pathway mediating the cerebellar immunomodulation. In this study, both lymphocyte percentage in peripheral leukocytes and lymphocyte proliferation induced by concanavalin A were reduced by the bilateral IN lesions with kainic acid. Anterograde tracing of nerve tracts with biotinylated dextran amine (BDA) from the cerebellum to the hypothalamus revealed that the BDA-labeled fibers from the cerebellar IN neurons traveled through superior cerebellar peduncle (SCP), crossed in SCP decussation, and primarily terminated in lateral hypothalamic area (LHA). Retrograde tracing with wheat germ agglutinin-horseradish peroxidase from the LHA to the cerebellar IN combined with immunohistochemistry for gamma-aminobutyric acid (GABA) or glutamate in the cerebellar sections displayed that the neuronal projections from the cerebellar IN to the LHA mostly were GABAergic. Blockage of GABA(A) receptors in the LHA with hydrastine led to a reduction in the lymphocyte percentage and proliferation, similar to the IN lesions. These results show a direct GABAergic projection from cerebellar IN to LHA and suggest that the projection mediates cerebellar immunomodulation.
authors.affiliation: Department of Physiology, School of Medicine, Nantong University, Nantong, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Bei-Bei
authors.initials: BB
authors.lastname: Cao
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Peng
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Qiu
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002529:Cerebellar Nuclei / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D004525:Efferent Pathways / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D007026:Hypothalamic Area, Lateral / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D015213:Neuroimmunomodulation / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D005680:gamma-Aminobutyric Acid