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The Korean Journal of Pathology 2000;34(6): 419-430.
Histopathologic Change and Apoptotic Profile in Basal Ganglia of Rat Induced by Manganese Administration.
Chang Won Ha, Jong Im Lee, Jung Ran Kim, Tae Jung Jang, Ki Kwon Kim, Dong Hoon Kim
Department of Pathology, College of Medicine, Dong Guk University, and Section of Cancer Research, Medical Institute of Dong Guk University, Kyung-Ju 780-714, Korea.
ABSTRACT
Mn (manganese) is known to induce Parkinsonian neurological disorder. Several lines of evidence suggest that apoptosis is involved not only in physiological cell death during normal development but also in neurodegenerative disease. The mechanism of Mn induced cell death remains poorly understood. In the present study, we evaluated the morphologic changes and apoptotic profile in basal ganglia using rat model of Mn toxicity. The rats were divided into three groups: the first group was a control; the second group was subdivided by administration dosage of Mn into group A (5, 10 mg MnC12/ kg) and group B (20, 40 mg MnC12/kg). The rats of each subgroup received a injection of Mn via tail vein every week for 4 weeks. The second group received 4 repeated injection of 10 mg MnC12/kg in the same manner and the rats were sacrificed at day 1, 3 & 7 in group I and at day 10, 21, 42, and 90 in group II after the last injection. A significant loss of neuron and gliosis were observed in the basal ganglia in the experimental groups (p<0.05), which were more pronounced in group II than in the control or group I. No significant difference in number of nerve cells or degree of gliosis was identified in the substantia nigra. Apoptotic cells were also increased in basal ganglia of experimental groups and appeared among neurons (10%), glial cells (10%), and endothelial cells (60%). Apoptotic figures were consistently noted through the entire experimental period after Mn injection in basal ganglia. In conclusion, these results demonstrate that Mn-induced cytopathic insult affects various cell types in basal ganglia and shows variable sensitivity in the different regions of brain, especially in the apoptotic cell death of the neuron. The overaccumulation of Mn in the brain might be attributed from the breakdown of blood-brain barrier due to the injury through the apoptosis.
Key Words: Rat; Brain; Mn (manganese); Apoptosis; Blood-brain barrier
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