Perinatal exposure to aluminum alters neuronal nitric oxide synthase expression in the frontal cortex of rat offspring.
Disturbance of the neuronal nitric oxide signaling pathway by chronic exposure to aluminum (Al) in drinking water may be a causal factor of neurological disorders in offspring. In order to investigate the relationship between Al administration and expression of neuronal nitric oxide synthase (nNOS), the numbers and distribution patterns of nNOS-immunoreactive neurons were examined in the frontal cortex of offspring after exposure to 0, 5, and 10 mM of Al in drinking water during prenatal and neonatal periods. At the bregma 0.20 level, the number of nNOS-positive neurons was significantly increased (10%) and decreased (17%) following exposure to 5 and 10 mM of Al in drinking water, respectively. The change was more severe in the upper layer than in deep layer of the cortex. In contrast, at the bregma -2.80 level, the number and distribution pattern was not significantly changed following exposure to Al. These data suggest that Al toxicity may be mediated through disturbances to the nitric oxide signaling pathway and exhibits a biphasic effect, especially in the frontal area of the cortex. In addition, the results suggest that impaired expression of nNOS plays an important role in the development of neurological syndrome caused by an exposure to Al during the early developmental stage.
Kim
Kisok
K
Division of Neurotoxicology, National Institute of Toxicological Research, 5 Nokbun-dong, Eunpyung-ku, 122-704 Seoul, South Korea. kimkisok@kfda.go.kr
D000535:Aluminum / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D005260:Female; D005625:Frontal Lobe / Q000033:anatomy & histology / Q000187:drug effects* / Q000201:enzymology; D007150:Immunohistochemistry; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011916:Rats, Inbred F344
D000535:Aluminum; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat