ovalbumin and Nerve-Degeneration

A recent study from our research group showed that repeated exposure to low-level formaldehyde (FA) increases the production of nerve growth factor, involving the survival and maintenance of neurons, in the hippocampus of immunized mice. In the present study, we examined the effects of FA on apoptotic mechanisms regulating survival and death of cells and on N-methyl-D-aspartate (NMDA) receptors related to hippocampal functions in the mouse hippocampus.. Western blot analyses were performed for Bcl-2, Bax and NMDA receptor subtypes 2A and 2B of the hippocampus taken from C3H mice exposed to 0 or 400 ppb of FA with or without ovalbumin (OVA) immunization. Immunohistochemical analysis for active caspase-3 was also carried out for these mice.. The ratio of Bcl-2 to Bax expression levels significantly increased with 400-ppb FA exposure in OVA-immunized mice but not in mice without OVA immunization, although differences in each protein level were not significant among groups. Active caspase- 3-immunoreactive cells were found in the hippocampus. However, the number was only a few and not significantly affected by FA exposure and OVA immunization. NMDA receptor type 2A and 2B expression levels of FA-exposed mice were sustained at comparative levels with those for the control mice with or without OVA immunization.. These results indicate that changes in the Bcl-2/Bax expression ratio, which occurs with low-level FA exposure and immunization and may follow enhancement of nerve growth factor production, exerts a protective effect against cell death by apoptosis.

Topics: Animals; Apoptosis Regulatory Proteins; bcl-2-Associated X Protein; Caspase 3; Cell Survival; Cytoprotection; Female; Formaldehyde; Hippocampus; Immunization; Mice; Mice, Inbred C3H; Nerve Degeneration; Nerve Growth Factor; Neurotoxins; Ovalbumin; Proto-Oncogene Proteins c-bcl-2; Receptors, N-Methyl-D-Aspartate; Up-Regulation

This study was undertaken to clarify the mechanisms by which C-fiber degeneration at neonatal stages exacerbates the inflammatory responses of rat airways. Rats were treated with capsaicin at neonatal stages and immunized with ovalbumin (OVA) at adult ages. Challenge of capsaicin-pretreated rats with OVA promoted a higher influx of neutrophils in bronchoalveolar lavage (BAL) fluid compared with the vehicle group. No significant differences were found for the other cell types. The increased adhesion of N-formyl-methionyl-leucyl-phenylalanine (fMLP; 0.1 microM)- and phorbol myristate acetate (PMA; 1 microM)-treated neutrophils to fibronectin-coated wells did not differ among vehicle- and capsaicin-pretreated rats. Additionally, fMLP (10 microM), platelet-activating factor (0.1 microM), and substance P (50 microM) induced a significant neutrophil chemotaxis, but no differences were found among vehicle and capsaicin groups. Increased levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, and leukotriene B4 in BAL fluid as well as higher expression of cytokine-induced neutrophil chemoattractant (CINC)-3 in lung homogenates were detected in the capsaicin group compared with vehicle group. In the capsaicin group, chronic treatment with compound 48/80 restored the TNF-alpha levels to control values and prevented the neutrophil influx in BAL fluid. The enhanced production of TNF-alpha, superoxide anion, and nitrite by isolated alveolar macrophages in response to lipopolysaccharide (3 microg/ml), PMA (10 nM), and/or zymosan (100 particles/cell) did not differ between vehicle- and capsaicin-pretreated rats. In conclusion, chronic neuropeptide depletion promoted by neonatal capsaicin treatment up-regulates airways mast cells, which upon activation by antigen at adult ages, release large amounts of cytokines such as TNF-alpha and CINC-3 that accounts for the massive airways neutrophil infiltration.

Topics: Animals; Animals, Newborn; Bronchoalveolar Lavage Fluid; Capsaicin; Cell Adhesion; Chemotaxis, Leukocyte; Cytokines; Female; Gene Expression Regulation; Leukocyte Count; Nerve Degeneration; Nerve Fibers, Unmyelinated; Neutrophil Infiltration; Nitric Oxide; Ovalbumin; Oxidants; Pulmonary Alveoli; Rats; Rats, Wistar; Respiratory Hypersensitivity; RNA, Messenger; Superoxides

Nigrostriatal degeneration, the pathological hallmark of Parkinson's disease (PD), is mirrored by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication. MPTP-treated animals show the common behavioral, motor, and pathological features of human disease. We demonstrated previously that adoptive transfer of Copaxone (Cop-1) immune cells protected the nigrostriatal dopaminergic pathway in MPTP-intoxicated mice. Herein, we evaluated this protection by quantitative proton magnetic resonance spectroscopic imaging (1H MRSI). 1H MRSI performed in MPTP-treated mice demonstrated that N-acetyl aspartate (NAA) was significantly diminished in the substantia nigra pars compacta (SNpc) and striatum, regions most affected in human disease. When the same regions were coregistered with immunohistochemical stains for tyrosine hydroxylase, numbers of neuronal bodies and termini were similarly diminished. MPTP-intoxicated animals that received Cop-1 immune cells showed NAA levels, in the SNpc and striatum, nearly equivalent to PBS-treated animals. Moreover, adoptive transfer of immune cells from ovalbumin-immunized to MPTP-treated mice failed to alter NAA levels or protect dopaminergic neurons and their projections. These results demonstrate that 1H MRSI can evaluate dopaminergic degeneration and its protection by Cop-1 immunization strategies. Most importantly, the results provide a monitoring system to assess therapeutic outcomes for PD.

Topics: Adoptive Transfer; Animals; Aspartic Acid; Cell Count; Chromatography, High Pressure Liquid; Corpus Striatum; Dopamine; Glatiramer Acetate; Immunization; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Mice; Microglia; MPTP Poisoning; Myelin Basic Protein; Nerve Degeneration; Nerve Tissue Proteins; Ovalbumin; Parkinsonian Disorders; Peptides; Substantia Nigra; T-Lymphocyte Subsets; Tyrosine 3-Monooxygenase

This study analyzes how the antigen specificity, the subtype, and the activation state of T cells modulate their recently discovered neuroprotective potential. We assessed the prevention from neuronal damage in organotypic entorhinal-hippocampal slice cultures after co-culture with Th1 and Th2 cells either specific for myelin basic protein (MBP) or ovalbumin (OVA). We found that MBP-specific Th2 cells were the most effective in preventing central nervous system (CNS) tissue from secondary injury. This neuroprotective T cell effect appears to be mediated by soluble factors. After stimulation with phorbol myristate acetate and ionomycin, all T cells were most effective in preventing neuronal death. Our data show that the T cell subtype and activation state are important features in determining the neuroprotective potential of these cells.

Topics: Animals; Animals, Newborn; Brain; Brain Injuries; Cell Survival; Chemotaxis, Leukocyte; Contact Inhibition; Cytokines; Epitopes; Mice; Mice, Inbred BALB C; Myelin Basic Protein; Nerve Degeneration; Neurons; Ovalbumin; Tetradecanoylphorbol Acetate; Th1 Cells; Th2 Cells

1. The effect of denervation on the anaphylactic contraction of the diaphragm from actively sensitized guinea pig has been studied. 2. The section of the phrenic nerve took place at cervical and thoracic levels. The sensitization of the animal took place several days before sectioning, simultaneously with denervation and after denervation. 3. The anaphylactic contractions were observed from the fourth day after thoracic denervation, and from the sixth day when denervation was in the cervical region. 4. The hypersensitivity to ACh in the denervated diaphragmatic muscle was present 24 hr after sectioning the phrenic nerve and reached its maximum 3-4 days after. 5. These results support the idea that denervation caused some changes in the membrane of the skeletal muscle fibres to allow the fixation of antibodies. These denervation changes are dependent on the length of the peripheral nerve left to degenerate. Anaphylactic contractions appeared earlier in those animals where phrenic nerve sections were closer to the diaphragmatic muscle.

Topics: Acetylcholine; Anaphylaxis; Animals; Diaphragm; Guinea Pigs; Histamine; Male; Muscle Denervation; Nerve Degeneration; Nerve Fibers; Ovalbumin; Phrenic Nerve

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Animals; Brain; Demyelinating Diseases; Encephalomyelitis, Autoimmune, Experimental; Freund's Adjuvant; Guinea Pigs; Myelin Sheath; Nerve Degeneration; Ovalbumin; Spinal Cord