Cerebellar ataxia induced by 3-AP affects immunological function.

Abstract

OBJECTIVE:

We previously showed that the cerebellum modulates the immune system. Here we determined whether cerebellar ataxia alters immunological function to further demonstrate an involvement of the cerebellum in immune modulation.

METHODS:

Neurotoxin 3-acetylpyridine (3-AP) was intraperitoneally injected in rats to induce cerebellar ataxia. Behavior and motor coordination were tested on day 7 following 3-AP injection. Nissl staining and high-performance liquid chromatography (HPLC) were used to determine neuronal loss and neurotransmitter contents, respectively, in all the three cerebellar nuclei, fastigial nucleus (FN), interposed nucleus (IN) and dentate nucleus (DN). T and B lymphocyte differentiation and function were measured by flow cytometry, Western blot and ELISA.

RESULTS:

3-AP induced motor discoordination and locomotor reduction. In all the three cerebellar nuclei, FN, IN and DN, there was a neuronal loss and a decrease in contents of glutamate and GABA (but not glycine) after 3-AP injection. Importantly, CD4+ T cells, but not CD8+ T cells, were increased by the 3-AP treatment. Moreover, interferon (IFN)-γ-producing cells and interleukin (IL)-17-producing cells were decreased in cerebellar ataxia rats, but IL-4-producing cells and CD25-expressing cells were increased. Expression of the T helper (Th)1- and Th17-related cytokines, IFN-γ, IL-2, IL-17 and IL-22, was downregulated in CD4+ cells in cerebellar ataxia rats, while expression of the Th2 and regulatory T (Treg)-related cytokines, IL-4, IL-5, IL-10 and transforming growth factor (TGF)-β, was upregulated. Furthermore, B lymphocyte number and anti-bovine serum albumin (BSA) IgM and IgG antibody levels were elevated in cerebellar ataxia.

CONCLUSION:

Cerebellar ataxia alters cellular and humoral immunity.

• Authors: Yong-Ying Jiang, Bei-Bei Cao, Xiao-Qin Wang, Yu-Ping Peng, Yi-Hua Qiu
• Journal: Neuro endocrinology letters (Neuro Endocrinol Lett) Vol. 36 Issue 3 Pg. 246-56 ( 2015) ISSN: 0172-780X [Print] Sweden
• PMID: 26313392 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Topics

• Animals
• Cerebellar Ataxia (chemically induced, immunology, metabolism)
• Disease Models, Animal
• Immunity, Cellular (immunology)
• Immunity, Humoral (immunology)
• Male
• Rats
• Rats, Sprague-Dawley