Cerebellar Fastigial Nuclear Glutamatergic Neurons Regulate Immune Function via Hypothalamic and Sympathetic Pathways

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• 作者：Bei-Bei Cao ; Yan Huang ; Yong-Ying Jiang ; Yi-Hua Qiu…
• 关键词：Cerebellar fastigial nucleus ; Hypothalamus ; Cerebellar ; hypothalamic projection ; Glutamatergic neurons ; Sympathetic nerves ; Lymphocytes
• 刊名：Journal of Neuroimmune Pharmacology
• 出版年：2015
• 出版时间：March 2015
• 年：2015
• 卷：10
• 期：1
• 页码：162-178
• 全文大小：6,049 KB
• 参考文献：1. Adkins B, Guevara P, Rose S (2006) Thymic and extrathymic contributions to T helper cell function in murine neonates. Haematol Rep 2:9-3
  2. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2002) Molecular biology of the cell, 4th edn. Garland Science, New York
  3. Baciu I, Hriscu M, Saulea G (2003) Hypothalamic mechanisms of immunity. Int J Neurosci 113:259-77 CrossRef
  4. Bao JY, Huang Y, Wang F, Peng YP, Qiu YH (2007) Expression of alpha-AR subtypes in T lymphocytes and role of the alpha-ARs in mediating modulation of T cell function. Neuroimmunomodulation 14:344-53 CrossRef
  5. Behar KL, Rothman DL (2001) In vivo nuclear magnetic resonance studies of glutamate-gamma-aminobutyric acid-glutamine cycling in rodent and human cortex: the central role of glutamine. J Nutr 131:2498S-504S
  6. Bellavance MA, Rivest S (2012) The neuroendocrine control of the innate immune system in health and brain diseases. Immunol Rev 248:36-5 CrossRef
  7. Bellinger DL, Millar BA, Perez S, Carter J, Wood C, ThyagaRajan S, Molinaro C, Lubahn C, Lorton D (2008) Sympathetic modulation of immunity: relevance to disease. Cell Immunol 252:27-6 CrossRef
  8. Bienkowski MS, Rinaman L (2011) Immune challenge activates neural inputs to the ventrolateral bed nucleus of the stria terminalis. Physiol Behav 104:257-65 CrossRef
  9. Cao BB, Han XH, Huang Y, Qiu YH, Peng YP (2012) The hypothalamus mediates the effect of cerebellar fastigial nuclear glutamatergic neurons on humoral immunity. Neuroendocrinol Lett 33:393-00
  10. Cao BB, Huang Y, Lu JH, Xu FF, Qiu YH, Peng YP (2013) Cerebellar fastigial nuclear GABAergic projections to the hypothalamus modulate immune function. Brain Behav Immun 27:80-0 CrossRef
  11. Cavdar S, San T, Aker R, Sehirli U, Onat F (2001) Cerebellar connections to the dorsomedial and posterior nuclei of the hypothalamus in the rat. J Anat 198:37-5 CrossRef
  12. Demirtas-Tatlidede A, Freitas C, Pascual-Leone A, Schmahmann JD (2011) Modulatory effects of theta burst stimulation on cerebellar nonsomatic functions. Cerebellum 10:495-03 CrossRef
  13. Dietrichs E, Haines DE, Roste GK, Roste LS (1994) Hypothalamocerebellar and cerebellohypothalamic projections: circuits for regulating nonsomatic cerebellar activity? Histol Histopathol 9:603-14
  14. Evrard HC, Craig AD (2008) Retrograde analysis of the cerebellar projections to the posteroventral part of the ventral lateral thalamic nucleus in the macaque monkey. J Comp Neurol 508:286-14 CrossRef
  15. Ghoshal D, Sinha S, Sinha A, Bhattacharyya P (1998) Immunosuppressive effect of vestibulo-cerebellar lesion in rats. Neurosci Lett 257:89-2 CrossRef
  16. Green-Johnson JM, Zalcman S, Vriend CY, Nance DM, Greenberg AH (1995) Suppressed T cell and macrophage function in the “reeler-rl/rl) mutant, a murine strain with elevated cerebellar norepinephrine concentration. Brain Behav Immun 9:47-0 CrossRef
  17. Haines DE, May PJ, Dietrichs E (1990) Neuronal connections between the cerebellar nuclei and hypothalamus in Macaca fascicularis: cerebello-visceral circuits. J Comp Neurol 299:106-22 CrossRef
  18. Haines DE, Dietrichs E, Mihailoff GA, McDonald EF (1997) The cerebellar-hypothalamic axis: basic circuits and clinical observations. Int Rev Neurobiol 41:83-07 CrossRef
  19. Haroian AJ, Massopust LC, Young PA (1981) Cerebellothalamic
• 刊物主题：Neurosciences; Immunology; Pharmacology/Toxicology; Virology; Cell Biology;
• 出版者：Springer US
• ISSN：1557-1904

文摘

We previously have shown that cerebellar fastigial nucleus (FN) modulates immune function, but pathways or mechanisms underlying this immunomodulation require clarification. Herein, an anterograde and retrograde tracing of nerve tracts between the cerebellar FN and hypothalamus/thalamus was performed in rats. After demonstrating a direct cerebellar FN-hypothalamic/thalamic glutamatergic projection, 6-diazo-5-oxo-L-norleucine (DON), an inhibitor of glutaminase that catalyzes glutamate synthesis, was injected bilaterally in the cerebellar FN and simultaneously, D,L-threo-β-hydroxyaspartic acid (THA), an inhibitor of glutamate transporters on cell membrane, was bilaterally injected in the lateral hypothalamic area (LHA) or the ventrolateral (VL) thalamic nucleus. DON treatment in the FN alone decreased number of glutamatergic neurons that projected axons to the LHA and also diminished glutamate content in both the hypothalamus and the thalamus. These effects of DON were reduced by combined treatment with THA in the LHA or in the VL. Importantly, DON treatment in the FN alone attenuated percentage and cytotoxicity of natural killer (NK) cells and also lowered percentage and cytokine production of T lymphocytes. These DON-caused immune effects were reduced or abolished by combined treatment with THA in the LHA, but not in the VL. Simultaneously, DON treatment elevated level of norepinephrine (NE) in the spleen and mesenteric lymphoid nodes, and THA treatment in the LHA, rather than in the VL, antagonized the DON-caused NE elevation. These findings suggest that glutamatergic neurons in the cerebellar FN regulate innate and adaptive immune functions and the immunomodulation is conveyed by FN-hypothalamic glutamatergic projections and sympathetic nerves that innervate lymphoid tissues.