Cilia and flagella are ancient, evolutionarily conserved organelles that project from cell surfaces to perform diverse biological roles, including whole-cell locomotion; movement of fluid; chemo-, mechano-, and photosensation; and sexual reproduction. Consistent with their stringent evolutionary conservation, defects in cilia are associated with a range of human diseases, such as primary ciliary dyskinesia, hydrocephalus, polycystic liver and kidney disease, and some forms of retinal degeneration. Recent evidence indicates that ciliary defects can lead to a broader set of developmental and adult phenotypes, with mutations in ciliary proteins now associated with nephronophthisis, Bardet-Biedl syndrome, Alstrom syndrome, and Meckel-Gruber syndrome. The molecular data linking seemingly unrelated clinical entities are beginning to highlight a common theme, where defects in ciliary structure and function can lead to a predictable phenotypic pattern that has potentially predictive and therapeutic value.

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Neural cells do not usually interact with immune cells because of the lack of major histocompatibility complex (MHC) antigen expression. Interferon-gamma (IFN-gamma) enables this interaction via induction of MHC antigen expression in neural cells. Thus, IFN-gamma is a critical cytokine for the development of central nervous system (CNS) pathologies. IFN-gamma, however, is considered to be produced exclusively by lymphoid cells. Here, we show for the first time that murine microglia produce IFN-gamma in response to IL-12 and/or IL-18, using RT-PCR detection of IFN-gamma mRNA and Western blotting and immunohistochemical analysis for cytoplasmic expression of IFN-gamma. Stimulation of microglia with IL-12 and IL-18 resulted in MHC class II mRNA expression in microglia. Since IL-12 and IL-18 are produced in the CNS by glial cells, these cytokines may play a critical role in the initiation of neural-immune cell interaction and the induction of autoimmune processes in the CNS via induction of IFN-gamma and MHC antigens.

Spinocerebellar ataxia type 6 (SCA6) was recently identified as a form of autosomal dominant spinocerebellar ataxia associated with a small CAG repeat expansion of the gene encoding an alpha 1 A-voltage-dependent calcium channel gene subunit on chromosome 19p13. In this study 50-microm-thick sections of cerebellar tissue from one patient with SCA6 were subjected to free-floating immunohistochemical staining with calbindin-D and parvalbumin antibodies. Severe loss of Purkinje cells was found, particularly in the vermis, and various morphological changes in Purkinje cells and their dendritic arborizations were demonstrated. Many of the remaining Purkinje cells were found to have heterotopic, irregularly shaped nuclei, an unclear cytoplasmic membrane outline, and somatic sprouts. Increased numbers of spine-like protrusions from swelling dendritic arborizations were found in the molecular layer. The axonal arrangement was disordered, and many torpedos were found in the granular layer and white matters. These morphological changes are completely different from those observed in paraneoplastic cerebellar degeneration (PCD) and multiple system atrophy (MSA) and are considered to be related to the genetic abnormality that causes abnormal development of Purkinje cells.