Prozac helps the HD mice

HD Lighthouse Contributing Editor's Comment: The finding that fluoxetine (Prozac) delays onset and cognitive loss in transgenic mice is an important one. The results are similar to the ones obtained in an earlier study with Paroxetine (Paxil). http://hdlighthouse.org/TreatmentNow/updates/0085-SSRItreatment.php Both Prozac and Paxil are SSRI antidepressants (selective serotin reuptake inhibitor) known to upregulate BDNF (brain derived neurotropic factor) which is reduced in HD patients.
--Marsha L. Miller, Ph.D.
Posted to the HDL: 06 Nov 2005

Anthony J. Hannan, Ph.D.

Huntington's disease (HD) is a neurodegenerative disorder caused by an expanded CAG trinucleotide repeat encoding an extended polyglutamine tract in the huntingtin protein. Affected individuals display progressive motor, cognitive and psychiatric symptoms (including depression), leading to terminal decline. Given that transgenic HD mice have decreased hippocampal cell proliferation and that a deficit in neurogenesis has been postulated as an underlying cause of depression, we hypothesized that decreased hippocampal neurogenesis contributes to depressive symptoms and cognitive decline in HD. Fluoxetine, a serotonin-reuptake inhibitor commonly prescribed for the treatment of depression, is known to increase neurogenesis in the dentate gyrus of wild-type mouse hippocampus. Here we show that hippocampal-dependent cognitive and depressive-like behavioural symptoms occur in HD mice, and that the administration of fluoxetine produces a marked improvement in these deficits. Furthermore, fluoxetine was found to rescue deficits of neurogenesis and volume loss in the dentate gyrus of HD mice.

The Press Release

Melbourne, Australia, scientists say they've found Prozac not only helps depression caused by Huntington's disease, but also improves learning and memory.

Howard Florey Institute scientists in Melbourne have found that fluoxetine (commonly marketed as Prozac®) not only improves depression in Huntington’s disease, but also improves learning and memory.

Dr Anthony Hannan and his team also found that fluoxetine restores the brain’s process of neurogenesis – the birth of new neurons – to normal levels, which helps delay the onset of the inherited fatal disease.

People with Huntington’s disease have progressive motor problems, cognitive deficits (dementia) and psychiatric symptoms (the most common is depression) that usually start to appear in mid-life. There is no cure and death usually results within 10 to 20 years of symptom onset, or faster in the childhood-onset form of the disease. The disease can be detected by genetic testing and it is caused by a mutation in a single gene and this defective gene is passed from parent to 50 percent of their children, who will inherit the disorder.

Dr Hannan said this discovery was an important step in developing effective treatments to delay the onset of symptoms and the progression of Huntington’s disease.

“Now that we’ve found fluoxetine improves memory problems, or dementia, as well as depression in mice with Huntington’s disease, further research can be conducted to see if the drug has the same benefits in humans with the disease,” Dr Hannan said.

“We have started discussing arrangements with colleagues to begin human trials to see if fluoxetine, and related drugs, are also effective treatments in people with the disease.”

“Fluoxetine’s ability to promote the birth of new neurons in the normal and Huntington’s brain provides new insight into the biological basis of depression, as well as other brain disorders involving dementia. It also suggests new applications for these antidepressant drugs,” he said.

During the study, mice with the Huntington’s gene and control mice were treated daily with either fluoxetine or saline. The mice were given cognitive tests to perform to determine the behavioural effects of the drug.

The scientists expected fluoxetine to improve the depressive-like symptoms, which they have shown for the first time in mice with Huntington’s disease, but were surprised that it also improved cognitive symptoms.

Dr Hannan’s findings will soon be published in the European Journal of Neuroscience.

Dr Hannan is internationally recognised for his research that proves mental and physical exercise can delay the onset of some degenerative brain disorders, including Huntington’s disease. Brain disorders that were previously thought to be 100 percent genetic can actually be delayed, which brings great hope to sufferers of Huntington’s disease.

Recent studies by Dr Hannan’s group have also shown that mice with Huntington’s disease actually display cognitive problems before the disease’s typical movement problems appear. These results were recently been published in the Journal of Neuroscience. He has also shown that in Huntington’s diseased brains, information processing between neurons is disrupted, but the neurons do not die, which means the brain may respond to new anti-dementia drugs that can restore memory.

Dr Hannan has just returned from Austria where he gave a special lecture on these findings and was presented with the Young Scientist Lecturer Award from the International Society of Neurochemistry. He also recently won two Australian Museum Eureka Prizes; the British Council Eureka Prize for Inspiring Science, as well as the inaugural Eureka People’s Choice Award.

Tracked on the Lighthouse:
antidepressant
SSRI

Source: Eur J Neurosci. 2005 Oct;22(8):2081-8.

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