Effect of Cerebellohypothalamic Glutamatergic Projections on Immune Function
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- 作者：Jian-Hua Lu (1) (2)
Hai-Nv Mao (2)
Bei-Bei Cao (2)
Yi-Hua Qiu (2)
Yu-Ping Peng (2) - 关键词：Cerebellar interposed nucleus ; Cerebellohypothalamic glutamatergic projection ; Hypothalamus ; Lymphocyte ; Immune function
- 刊名：The Cerebellum
- 出版年：2012
- 出版时间：December 2012
- 年：2012
- 卷：11
- 期：4
- 页码：905-916
- 全文大小：1153KB
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Hai-Nv Mao (2)
Bei-Bei Cao (2)
Yi-Hua Qiu (2)
Yu-Ping Peng (2)
1. School of Biological & Basic Medical Science, Soochow University, Suzhou, China
2. Department of Physiology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong, 226001, China - ISSN：1473-4230
文摘
Our previous work has shown that lesions of the cerebellar interposed nuclei (IN) suppress immune cell functions. Since there is no direct structural connection between the cerebellum and immune system, we explored the pathway mediating the cerebellar immunomodulation at the profile of cerebellohypothalamic projections to understand this modulation. Anterograde tracing of nerve tracts from the cerebellar IN to the hypothalamus was conducted by injection of anterograde tracer dextran-texas red (dextran-TR) in the cerebellar IN. We observed that dextran-TR-labeled nerve fibers, which were sent by cerebellar IN neurons, traveled in the superior cerebellar peduncle (SCP), crossed in SCP decussation, and entered the hypothalamus. In the hypothalamus, the fibers mostly terminated in the lateral hypothalamic area (LHA). Retrograde tracing by injection of retrograde tracer fluoro-ruby (FR) in the LHA found that FR-labeled neurons appeared in contralateral cerebellar IN. Fluorescent immunohistochemistry for glutamate revealed that many of the FR-labeled neurons were glutamatergic. These results demonstrate a direct glutamatergic projection from the cerebellar IN to the LHA. Reduction of the cerebellohypothalamic glutamatergic projections by microinjection of 6-diazo-5-oxo-l-norleucine (DON), an inhibitor of glutaminase for glutamate synthesis, in bilateral cerebellar IN led to suppression of peripheral lymphocyte number, T lymphocyte proliferation, and serum anti-sheep red blood cell IgM level. But the DON injection in the cerebellar cortex that does not send axons to the hypothalamus did not significantly alter all the immune parameters. These findings suggest that cerebellohypothalamic glutamatergic projection modulates immune function, and that via the pathway, the cerebellum implements its immunoregulatory effect.