galactocerebroside and Nerve-Degeneration

Meta-analysis studies showed that smokers have increased risk for developing Alzheimer's disease (AD) compared with non-smokers, and neuroimaging studies revealed that smoking damages white matter structural integrity.. The present study characterizes the effects of side-stream (second hand) cigarette smoke (CS) exposures on the expression of genes that regulate oligodendrocyte myelin-synthesis, maturation, and maintenance and neuroglial functions.. Adult male A/J mice were exposed to air (8 weeks; A8), CS (4 or 8 weeks; CS4, CS8), or CS8 followed by 2 weeks recovery (CS8 + R). The frontal lobes were used for histology and qRT-PCR analysis.. Luxol fast blue, Hematoxylin and Eosin stained histological sections revealed CS-associated reductions in myelin staining intensity and narrowing of the corpus callosum. CS exposures broadly decreased mRNA levels of immature and mature oligodendrocyte myelin-associated, neuroglial, and oligodendrocyte-related transcription factors. These effects were more prominent in the CS8 compared with CS4 group, suggesting that molecular abnormalities linked to white matter atrophy and myelin loss worsen with duration of CS exposure. Recovery normalized or upregulated less than 25% of the suppressed genes; in most cases, inhibition of gene expression was either sustained or exacerbated.. CS exposures broadly inhibit expression of genes needed for myelin synthesis and maintenance. These adverse effects often were not reversed by short-term CS withdrawal. The results support the hypothesis that smoking contributes to white matter degeneration, and therefore could be a key risk factor for a number of neurodegenerative diseases, including AD.

Topics: 2',3'-Cyclic-Nucleotide Phosphodiesterases; AC133 Antigen; Animals; Antigens, CD; Brain; Disease Models, Animal; Galactosylceramides; Gene Expression Regulation; Glycoproteins; Leukoencephalopathies; Male; Mice; Nerve Degeneration; Nerve Tissue Proteins; Neuroglia; Neurons; Nicotiana; Oligodendroglia; Peptides; Smoking; Transcription Factors

There is suggestive but inconclusive evidence for a contribution of T cells and antimyelin antibodies to the pathogenesis of the Guillain-Barré polyneuropathy. We have studied the potential synergism of cellular and humoral immunity in the adoptive transfer model of EAN. EAN was induced in Lewis rats by injecting varying doses of P2 peptide (SP26)-sensitized T lymphocytes. Disease severity was dose-dependent. The addition of intravenous GC-AB to a subclinical dose of SP26-sensitized T cells resulted in overt clinical disease and markedly enhanced demyelination. Intravenous injection of antibody alone had no effect. We conclude that activated neuritogenic T cells, while entering into peripheral nerves, alter the blood-nerve barrier, which gives circulating demyelinating antibodies access to the endoneurium. The observations support the concept of a synergistic role of T-cell autoimmunity and humoral responses in the inflammatory demyelination of Lewis rat EAN.

Topics: Animals; Antibodies; Axons; Demyelinating Diseases; Edema; Female; Galactosylceramides; Ganglia, Spinal; Immunization, Passive; Lymphocyte Activation; Macrophages; Male; Motor Neurons; Myelin Basic Protein; Myelin P2 Protein; Nerve Degeneration; Neurilemma; Neuritis, Autoimmune, Experimental; Neurons, Afferent; Rabbits; Rats; Rats, Inbred Lew; Sciatic Nerve; Spinal Cord; Spinal Nerve Roots; T-Lymphocytes