Comparison of immunoreactivities in 4-HNE and superoxide dismutases in the cervical and the lumbar spinal cord between adult and aged dogs

Aging shows slowly progressive changes and is associated with many functional and morphological changes in the central nervous system. The accumulation of reactive oxygen species causes age-related deterioration in neuronal function and contributes to the increase of disease susceptibility during normal aging. In the present study, we compared the neuronal distribution and immunoreactivities of 4-hydroxy-2E-nonenal (4-HNE, end product of lipid peroxidation), and superoxide dismutase 1 (SOD1) and SOD2 in the cervical and lumbar spinal cord between adult (2-3 years) and aged (10-12 years) dogs. No significant change in neuronal morphology was observed after cresyl violet staining. The number of NeuN (a marker for neurons)-immunoreactive neurons was not significantly changed in the aged group compare to the adult group. In addition, we could not find Fluoro-Jade B (a marker for degenerating neurons) positive cells in both the adult and aged dogs. However, numbers of 4-HNE-, SOD1- and SOD2-immunoreactive cells were significantly increased in both the cervical and lumbar spinal cord of the aged dog: The increase rates of these cells in the aged spinal cord were higher in the lumbar level than the cervical level. In brief, 4-HNE, SOD1 and SOD2 levels are much increased in the aged spinal cord compared to the adult spinal cord.

[1]  Paul G. Ince,et al.  Immunocytochemical study of the distribution of the free radical scavenging enzymes CU/ZN superoxide dismutase (SOD1); MN superoxide dismutase (MN SOD) and catalase in the normal human spinal cord and in motor neuron disease , 1997, Journal of the Neurological Sciences.

[2]  Ws El-Masry,et al.  Aging and spinal cord injury , 2001 .

[3]  M. C. Vega,et al.  Age-related changes of the GABA-B receptor in the lumbar spinal cord of male rats and penile erection. , 2006, Life sciences.

[4]  Eric Klann,et al.  Overexpression of SOD-2 reduces hippocampal superoxide and prevents memory deficits in a mouse model of Alzheimer's disease , 2009, Proceedings of the National Academy of Sciences.

[5]  L. Garcia-Segura,et al.  Decrease in PTEN and increase in Akt expression and neuron size in aged rat spinal cord , 2010, Experimental Gerontology.

[6]  A. Sharan,et al.  Mortality rates in geriatric patients with spinal cord injuries. , 2007, Journal of neurosurgery. Spine.

[7]  Michael G Fehlings,et al.  Effect of age on spinal cord injury. , 2007, Journal of neurosurgery. Spine.

[8]  Ke Cui,et al.  Role of oxidative stress in neurodegeneration: recent developments in assay methods for oxidative stress and nutraceutical antioxidants , 2004, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[9]  M Raes,et al.  Importance of Se-glutathione peroxidase, catalase, and Cu/Zn-SOD for cell survival against oxidative stress. , 1994, Free radical biology & medicine.

[10]  C J Epstein,et al.  Manganese Superoxide Dismutase Mediates the Early Release of Mitochondrial Cytochrome C and Subsequent DNA Fragmentation after Permanent Focal Cerebral Ischemia in Mice , 1999, The Journal of Neuroscience.

[11]  J E Kiwerski,et al.  Factors contributing to the increased threat to life following spinal cord injury , 1993, Paraplegia.

[12]  Robert M. Santer,et al.  Age-associated changes in the monoaminergic innervation of rat lumbosacral spinal cord , 2003, Brain Research.

[13]  A F Junod,et al.  Response of human endothelial cell antioxidant enzymes to hyperoxia. , 1992, American journal of respiratory cell and molecular biology.

[14]  Nelson Merino,et al.  Delayed treatment with nimesulide reduces measures of oxidative stress following global ischemic brain injury in gerbils , 2003, Neuroscience Research.

[15]  Yoshihisa Naito,et al.  The plasma superoxide scavenging activity in canine cancer and hepatic disease. , 2003, The Journal of veterinary medical science.

[16]  In Koo Hwang,et al.  Differences in lipid peroxidation and Cu,Zn-superoxide dismutase in the hippocampal CA1 region between adult and aged dogs. , 2008, The Journal of veterinary medical science.

[17]  Ganesan Murali,et al.  Age-related oxidative protein damages in central nervous system of rats: modulatory role of grape seed extract , 2005, International Journal of Developmental Neuroscience.

[18]  M. Molinari,et al.  Effects on age on spinal cord lesion patients' rehabilitation , 2003, Spinal Cord.

[19]  In Koo Hwang,et al.  Comparison of Ionized Calcium-binding Adapter Molecule 1-Immunoreactive Microglia in the Spinal Cord Between Young Adult and Aged Dogs , 2010, Neurochemical Research.

[20]  Jurate Lasiene,et al.  Age‐related myelin dynamics revealed by increased oligodendrogenesis and short internodes , 2009, Aging cell.

[21]  B. Ames,et al.  The free radical theory of aging matures. , 1998, Physiological reviews.

[22]  Carl W. Cotman,et al.  Voluntary running attenuates age-related deficits following SCI , 2008, Experimental Neurology.

[23]  F. Levi-Schaffer,et al.  Role of reactive oxygen species (ROS) in apoptosis induction , 2000, Apoptosis.

[24]  Xi Chen,et al.  Mitochondrial dysfunction and Alzheimer's disease. , 2006, Current Alzheimer research.

[25]  Melissa Miranda,et al.  Inhibitory role for GABA in autoimmune inflammation , 2010, Proceedings of the National Academy of Sciences.

[26]  Lingyun Wu,et al.  Oxidative stress and aging: is methylglyoxal the hidden enemy? , 2010, Canadian journal of physiology and pharmacology.

[27]  H. Sies,et al.  Oxidative stress: oxidants and antioxidants , 1997, Experimental physiology.

[28]  Laia Acarin,et al.  Neuroprotection from NMDA excitotoxic lesion by Cu/Zn superoxide dismutase gene delivery to the postnatal rat brain by a modular protein vector , 2006, BMC Neuroscience.

[29]  Y. Ng,et al.  Distinct roles of oxidative stress and antioxidants in the nucleus dorsalis and red nucleus following spinal cord hemisection , 2005, Brain Research.

[30]  R. Reiter,et al.  Oxidative processes and antioxidative defense mechanisms in the aging brain 1 , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[31]  E. Portiansky,et al.  Changes in carbohydrate expression in the cervical spinal cord of rats during aging , 2009, Neuropathology : official journal of the Japanese Society of Neuropathology.

[32]  E. Joosten,et al.  Local acute application of BDNF in the lesioned spinal cord anti-inflammatory and anti-oxidant effects , 2004, Neuroreport.

[33]  Nobuhiko Hoshi,et al.  Age-related change and its sex differences in histoarchitecture of the hypothalamic suprachiasmatic nucleus of F344/N rats , 2005, Experimental Gerontology.

[34]  Elizabeth Head,et al.  The canine (dog) model of human aging and disease: dietary, environmental and immunotherapy approaches. , 2008, Journal of Alzheimer's disease : JAD.

[35]  Makoto Kawase,et al.  Mitochondrial Susceptibility to Oxidative Stress Exacerbates Cerebral Infarction That Follows Permanent Focal Cerebral Ischemia in Mutant Mice with Manganese Superoxide Dismutase Deficiency , 1998, The Journal of Neuroscience.

[36]  L. Schmued,et al.  Fluoro-Jade B: a high affinity fluorescent marker for the localization of neuronal degeneration , 2000, Brain Research.

[37]  Placido Bramanti,et al.  Increased oxidative-related mechanisms in the spinal cord injury in old rats , 2006, Neuroscience Letters.

[38]  Pedro Pesini,et al.  Natural Non-Trasgenic Animal Models for Research in Alzheimer’s Disease , 2009, Current Alzheimer research.

[39]  E. Stadtman,et al.  Protein Oxidation in Aging, Disease, and Oxidative Stress* , 1997, The Journal of Biological Chemistry.

[40]  Barry Halliwell,et al.  Reactive Oxygen Species and the Central Nervous System , 1992, Journal of neurochemistry.