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DERT Papers of the Month

By Jerry Phelps
November 2006

Chronic Treatment with Nicotine Protects Against Parkinsonian Symptoms in Primates

NIEHS-supported researchers at The Parkinson's Institute report that long-term oral administration of nicotine to squirrel monkeys protects against Parkinson-like symptoms induced by exposure to the dopaminergic neurotoxin MPTP. These findings mirror human epidemiologic studies that suggest that smokers are less likely to develop Parkinson's disease than non-smokers.

The primates were administered nicotine in drinking water to produce blood nicotine levels within the range seen in cigarette smokers. Laboratory results suggest that nicotine acts to restore or maintain dopamine production in the substantia nigra region of the brain. These data further support a protective role of nicotine and support future studies to explore nicotine or compounds that act similarly as possible therapeutic agents for Parkinson's disease.

Citation: Quik M, Parameswaran N, McCallum SE, Bordia T, Bao S, McCormack A, Kim A, Tyndale RF, Langston JW, Di Monte DA. 2006. Chronic oral nicotine treatment protects against striatal degeneration in MPTP-treated primates. J Neurochem 98(6):1866-1875.

Functional MRI Demonstrates Impacts of Lead Exposure on Brain Organization

Bruce Lanphear and colleagues at the Cincinnati Children's Environmental Health Center report new findings related to childhood lead exposure. Using functional magnetic resonance imaging, they saw evidence of reorganization of the language centers of the brains of young adults with a history of childhood lead exposure.

Lead exposure is known to cause behavioral problems and learning deficits in children that persist into adulthood. The current study offers new findings that demonstrate a substantial adverse effect of lead on normal language centers and simultaneous recruitment of other brain regions. These results are among the first to suggest that lead exposure affects language ability and offer further confirmation of the deleterious effects of lead exposure on cognitive abilities.

Citation: Yuan W, Holland SK, Cecil KM, Dietrich KN, Wessel SD, Altaye M, Hornung RW, Ris MD, Egelhoff JC, Lanphear BP. 2006. The impact of early childhood lead exposure on brain organization: a functional magnetic resonance imaging study of language function. Pediatrics 118(3):971-977.

CD63: A Tissue Inhibitor of Metalloproteinase

Previously it was thought tissue inhibitors of the enzyme metalloproteinase-1 (TIMP-1) suppressed cancer metastasis. However, subsequent clinical studies linked increased TIMP-1 expression with poor prognosis in certain malignancies, including metastatic breast cancer. This NIEHS-supported research team at Wayne State University addressed the issue by investigating the role of TIMP-1 during breast cancer progression.

Dr. Hyeong-Reh Choi Kim's laboratory was one of the first research teams to report TIMP-1 as an inhibitor of apoptosis. Since this discovery, many investigators have suggested TIMP-1 regulates cell survival through its interaction with an unknown cell surface receptor. Dr. Kim's team identified CD63 as a cell surface-binding partner for TIMP-1, which is critical for human breast epithelial cell survival.

The study team acknowledges that future studies aimed at unveiling the functions of TIMP-1 at the molecular level would greatly enhance the understanding of breast cancer progression. This information may also be useful in designing other interventions.

Citation: Jung KK, Liu XW, Chirco R, Fridman R, Kim HR. 2006. Identification of CD63 as a tissue inhibitor of metalloproteinase-1 interacting cell surface protein. EMBO J 25(17):3934-3942.

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