Obesity is a major risk factor associated with a variety of diseases including cardiovascular disorders, diabetes and certain cancers. Little information exists, however, as to whether obesity modifies the response of the central nervous system (CNS) to neural injury. The purpose of the present study was to determine if obesity serves as a predisposing factor in modifying/mediating a neurot.oxic response. Leptin deficient (ob/ob) mice were used as a model of obesity and the dopaminergic neurotoxicants, 1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) and methamphetamine (METH) were used as neurotoxic insults. Tyrosine hydroxlase (TH) was used as an index of dopaminergic nerve terminal integrity and was assessed by a novel fluorescence-based ELISA and by immunoblot. Glialfibrillary acidic protein (GFAP) was used as an index of the glial reaction to terminal damage and was assessed by sandwich ELISA. Both MPTP and METH significantly decreased striatal TH levels in a time-dependent fashion in the striatum of wild and ob/ob mice. Basal levels of TH were 25% lower in ob/ob mice compared to wild type mice. By 48 hours post-dosing, MPTP reduced TH by approximately 70-75% in both wild type and ob/ob mice. METH resulted in nearly a 90 % decrease in ob/ob mice in comparison to 75% decrements in wild type controls. These data were in agreement with immunoblot results on the same samples. While both MPTP and METH induced a large (>600%) Increase in striatal GFAP of wild-type mice, this effect was attenuated (not exacerbated) in ob/ob mice. Basal levels of GF AP also were lower (25%) in ob/ob mice. The data indicate that METH-induced dopaminergic neurotoxicity (based on TH decreases) is enhanced in the obese (ob/ob) and that the leptin-deficient condition decreases the levels of TH and GF AP. The ob/ob mouse may not serve as an appropriate model for assessing the effects of obesity on toxic responses of the CNS.
Keywords
Risk factors; Risk analysis; Neurotoxicity; Central nervous system disorders; Nervous system disorders; Neurotoxic effects; Laboratory animals; Animals; Animal studies; Toxic effects
Publication Date
20000301
Document Type
Abstract
Fiscal Year
2000
Issue of Publication
1
ISSN
1096-6080
NIOSH Division
HELD
Source Name
The Toxicologist. Society of Toxicology 39th Annual Meeting, March 19-23, 2000, Philadelphia, Pennsylvania
Links with this icon indicate that you are leaving the CDC website.
The Centers for Disease Control and Prevention (CDC) cannot attest to the accuracy of a non-federal website.
Linking to a non-federal website does not constitute an endorsement by CDC or any of its employees of the sponsors or the information and products presented on the website.
You will be subject to the destination website's privacy policy when you follow the link.
CDC is not responsible for Section 508 compliance (accessibility) on other federal or private website.
For more information on CDC's web notification policies, see Website Disclaimers.
CDC.gov Privacy Settings
We take your privacy seriously. You can review and change the way we collect information below.
These cookies allow us to count visits and traffic sources so we can measure and improve the performance of our site. They help us to know which pages are the most and least popular and see how visitors move around the site. All information these cookies collect is aggregated and therefore anonymous. If you do not allow these cookies we will not know when you have visited our site, and will not be able to monitor its performance.
Cookies used to make website functionality more relevant to you. These cookies perform functions like remembering presentation options or choices and, in some cases, delivery of web content that based on self-identified area of interests.
Cookies used to track the effectiveness of CDC public health campaigns through clickthrough data.
Cookies used to enable you to share pages and content that you find interesting on CDC.gov through third party social networking and other websites. These cookies may also be used for advertising purposes by these third parties.
Thank you for taking the time to confirm your preferences. If you need to go back and make any changes, you can always do so by going to our Privacy Policy page.