Oxidative stress caused by ozone exposure induces loss of brain repair in the hippocampus of adult rats.
Oxidative stress is involved in many neurodegenerative diseases. Chronic ozone exposure causes a secondary increase of reactive oxygen species, which cause an oxidative stress state in the organism. Ozone is one of the main components of photochemical pollution. Our purpose was to test that oxidative stress caused by chronic low doses of ozone, by itself, alters adult neurogenesis and causes progressive neurodegeneration in the hippocampus, which actions lead to the loss of brain plasticity in the mature central nervous system of rats. Animals were exposed to an ozone-free air stream and for 15, 30, 60, and 90 days to low doses of ozone to cause oxidative stress. Each group was then tested by (1) a spectrophotometer test to quantify lipid peroxidation (LPO) levels; (2) immunohistochemistry testing against doublecortin, Neu-N, p53, microglia, and glial fibrillary acidic protein; (3) Western blot tests for doublecortin and Neu-N; and (4) a one-trial passive avoidance test. Our results indicated that ozone causes an increase of LPO levels, morphological changes in the nucleus and the cytoplasm, and cell swelling in neurons. The Western blot shows a decrease for Neu-N and doublecortin. Activated and later phagocytic microglia and an increased number of astrocytes were found. There was a memory deficiency positively related to the amount of ozone exposure. These alterations suggest that oxidative stress caused by low doses of ozone causes dysregulation of inflammatory processes, progressive neurodegeneration, chronic loss of brain repair in the hippocampus, and brain plasticity changes in the rat analogous to those seen in Alzheimer's disease.
Rivas-Arancibia
Selva
S
Departamento de Fisiología, Universidad Nacional Autónoma de México, AP 70-250, CP 04510 México D.F., México. srivas@unam.mx
Guevara-Guzmán
Rosalinda
R
López-Vidal
Yolanda
Y
Rodríguez-Martínez
Erika
E
Zanardo-Gomes
Margarete
M
Angoa-Pérez
Mariana
M
Raisman-Vozari
Rita
R
D000367:Age Factors; D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects*; D009473:Neuronal Plasticity / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009479:Neuropeptides / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010126:Ozone / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013053:Spectrophotometry; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D034961:Antigens, Nuclear; C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C546339:Rbfox3 protein, rat; D016159:Tumor Suppressor Protein p53; D010126:Ozone