Abstract Details

Title Vascular Endothelial Growth Factor Upregulation at the Blood-Brain Barrier after Subacute Methylmercury Intoxication in a Rat Model

Topic Neurotoxicology

Presentation(s) P06 - (-)

Poster/Presentation
Number 199

Objective

Background BACKGROUND: MeHg intoxication causes Hunter-Russell syndrome with clinical manifestations of cerebellar ataxia, vision disturbance, and sensory and auditory disturbances. The pathogenesis of MeHg intoxication, particularly the mechanism underlying selective neuronal degeneration, remains uncertain. The autopsy of human brains exposed to MeHg showed petechial hemorrhage and edema in the cerebellum, the site at which intense neuronal cell death occurs. This suggests that injury to the blood-brain barrier (BBB) is associated with the neuronal degeneration induced by MeHg.

Design/Methods DESIGN/METHODS: Six-week-old male Wistar rats were divided into 5 groups: a sham exposure group and groups that underwent 1, 2, 3, or 4 weeks of MeHg exposure. These rats were exposed to water or water containing 20 ppm MeHg. Brain tissue was harvested after 4 weeks. Cerebellums and 3 portions of the cerebrum (frontal, central, and occipital) were examined for VEGF expression via immunohistochemical staining. To investigate the distribution of induced VEGF expression, anti-RECA1 and GFAP antibodies were used. The MeHg content in each portion of the brain, changes in body weight, and changes in motor function represented by hind-limb crossing were also assessed.

Results RESULTS: Increased VEGF expression was observed, particularly in the cerebellum in rats exposed to MeHg for 4 weeks. VEGF expression was primarily observed in GFAP-positive cells but not in RECA1-positive cells. No differences were observed in MeHg content between the parts of the brain in any of the groups. Longer MeHg exposure was associated with lower motor functional scores and body weight.

Conclusions CONCLUSIONS: We confirmed the increased VEGF expression in the cerebellum of rats exposed to MeHg for 4 weeks. This upregulation was primarily observed in astrocytes, indicating that BBB injury via VEGF upregulation may be one of the mechanisms of the MeHg-induced selective neuronal degeneration.

Authors/Disclosures
Tetsuya Takahashi, PhD (Dept. of Neurology, Niigata University BRI) PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
Masatoyo Nishizawa, MD (Niigata University of Health and Welfare)	No disclosure on file
Bernhard G. Landwehrmeyer, MD (Ulm University Hospital)	Dr. Landwehrmeyer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ACADIA PHARMACEUTICALS INC, San Diego, CA. Dr. Landwehrmeyer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck Valby, Denmark. Dr. Landwehrmeyer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AOP Orphan Pharmaceuticals AG, Vienna, Austria. Dr. Landwehrmeyer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Remix Therapeutics, Inc., Cambridge, MA. Dr. Landwehrmeyer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for HSG Clinical Research, Inc. Dr. Landwehrmeyer has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for F. Hoffmann-La Roche Ltd, Basel, Switzerland. Dr. Landwehrmeyer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche Pharma AG, Grenzach/Whylen, Germany. Dr. Landwehrmeyer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis Pharma AG, Basel, Switzerland. The institution of Dr. Landwehrmeyer has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis Pharma AG, Basel, Switzerland. Dr. Landwehrmeyer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PTC Therapeutics, Inc., South Plainfield, NJ . Dr. Landwehrmeyer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Triplet Therapeutics, Inc. Cambridge, MA. Dr. Landwehrmeyer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Takeda Pharma. Dr. Landwehrmeyer has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche Pharma AG, Grenzach/Whylen, Germany. Dr. Landwehrmeyer has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for F. Hoffmann-La Roche Ltd, Basel, Switzerland. Dr. Landwehrmeyer has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis Pharma AG, Basel, Switzerland. The institution of Dr. Landwehrmeyer has received research support from CHDI Foundation. The institution of Dr. Landwehrmeyer has received research support from European Commission. The institution of Dr. Landwehrmeyer has received research support from German Federal Government BMBF. The institution of Dr. Landwehrmeyer has received research support from German Research Council DFG. Dr. Landwehrmeyer has received publishing royalties from a publication relating to health care. Dr. Landwehrmeyer has received publishing royalties from a publication relating to health care.
Takayoshi Shimohata, MD, FAAN (Department of Neurology, Gifu University)	Dr. Shimohata has nothing to disclose.

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