The hypothalamus mediates the effect of cerebellar fastigial nuclear glutamatergic neurons on humoral immunity.

OBJECTIVES: We explored effect of glutamatergic neurons in the fastigial nucleus (FN), one of three cerebellar nuclei, on humoral immunity and revealed that this effect was mediated by the hypothalamus via FN-hypothalamic glutamatergic transmission.

METHODS: Rats were immunized with bovine serum albumin (BSA). On the third day after the immunization, 6-diazo-5-oxo-L-norleucine (DON), an inhibitor of glutaminase for glutamate synthesis, was microinjected in bilateral FN and D,L-threo-β-hydroxyaspartic acid (THA), an inhibitor of glutamate transporters on plasma membrane, was microinjected in both sides of lateral hypothalamic area (LHA). Glutamate content in the hypothalamus was examined by high-performance liquid chromatography (HPLC). Flow cytometry and enzyme-linked immunosorbent assay (ELISA) were used to measure B lymphocyte percentage in mononuclear cells of peripheral blood and levels of anti-BSA IgM and IgG antibodies in the serum, respectively.

RESULTS: DON injection in bilateral FN reduced B lymphocyte percentage and anti-BSA IgM and IgG levels, and simultaneously decreased glutamate content in the hypothalamus. Combined treatment with DON in the FN and with THA in the LHA elevated B cell number and anti-BSA IgM and IgG levels and increased hypothalamic glutamate content compared with DON treatment alone. However, combined treatment with DON in the FN and with THA in the ventrolateral thalamic nuclei (VL) did not significantly alter DON-dependent changes in B cell number and antibody levels, although the co-treatment altered DON-dependent glutamate content in the thalamus.

CONCLUSION: Cerebellar FN glutamatergic neurons participate in modulation of humoral immunity and this effect is mediated by the hypothalamus via FN-hypothalamic glutamatergic transmission.