NEWS: 22/8/07 'Meth abuse may speed brain degeneration'

Meth abuse may speed brain degenerationFrom correspondents in New York
August 29, 2007

YOUNG people who abuse methamphetamines may put themselves at risk of parkinson-like movement disorders later in life, a new animal study suggests.

In experiments with mice, scientists found that animals deficient in a protein called glial cell line-derived neurotrophic factor (GDNF) were especially vulnerable to long-term movement problems after being exposed to the neurotoxic effects of a methamphetamine "binge".

GDNF is needed for the proper functioning of dopamine, a brain chemical involved in regulating movement. Both GDNF and dopamine are depleted in the brains of people with Parkinson's disease.

Because methamphetamines can damage dopamine-producing cells in the brain, researchers have speculated that young meth users may be at elevated risk of parkinson-like movement disorders as they age.

The new findings, reported in The Journal of Neuroscience, support that theory.

"The study in mice tells us that people who make less GDNF protein may be more vulnerable to the motor deficits caused by methamphetamine and that those effects may not be revealed until we get older," explained principal author Dr Jacqueline McGinty, a professor in the department of neurosciences at the Medical University of South Carolina in Charleston.

For their study, Dr McGinty and her colleagues used both normal mice and mice missing one of their genes for GDNF. Two weeks after being exposed to a meth binge, the animals tended to show dopamine depletion and other signs of brain damage, with the GDNF-deficient mice being especially vulnerable.

Similarly, these mice were more likely to have movement impairments when they were 12 months old - old age for rodents.

No one knows what percentage of the population has an abnormal GDNF gene, Dr McGinty said, but individuals certainly vary in how much GDNF protein their genes make.

It's possible, she and her colleagues said, that young people with naturally lower levels of the protein may be susceptible to long-term brain damage and Parkinson-like symptoms at an older age.

"Motor deficits during aging may be accelerated if young adults are exposed to an environmental toxin like methamphetamine," Dr McGinty said.

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Attenuated microglial activation mediates tolerance to the
neurotoxic effects of methamphetamine

Journal of Neurochemistry, 2005, 92, 790–797

David M. Thomas and Donald M. Kuhn

Abstract

Methamphetamine causes persistent damage to dopamine nerve endings of the striatum. Repeated, intermittent treatment of mice with low doses of methamphetamine leads to the development of tolerance to its neurotoxic effects. The mechanisms underlying tolerance are not understood but clearly involve more than alterations in drug bioavailability or reductions in the hyperthermia caused by methamphetamine. Microglia have been implicated recently as mediators of methamphetamine-induced neurotoxicity.

The purpose of the present studies was to determine if a tolerance regimen of methamphetamine would attenuate the microglial response to a neurotoxic challenge. Mice treated with a low-dose methamphetamine tolerance regimen showed minor reductions in striatal dopamine content and low levels of microglial activation.

When the tolerance regimen preceded a neurotoxic challenge of methamphetamine, the depletion of dopamine normally seen was significantly attenuated. The microglial activation that occurs after a toxic methamphetamine challenge was blunted likewise. Despite the induction of tolerance against drug-induced toxicity and microglial activation, a neurotoxic challenge with methamphetamine still caused hyperthermia.

These results suggest that tolerance to methamphetamine neurotoxicity is associated with attenuated microglial activation and they further dissociate its neurotoxicity from drug-induced hyperthermia.

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