AUG 31, 2017

Serotonin Transport and Dementia

WRITTEN BY: Brenda Kelley Kim

Serotonin is an essential neurotransmitter. It's a chemical that regulates some vital functions in the body like mood, appetite and sleep cycles. Lower levels of it have been linked to anxiety, depression and other neurological conditions, and medications that boost levels of serotonin are often used to treat imbalances. A new study from Johns Hopkins on patients with mild cognitive decline and memory loss suggests that some forms of dementia could be the result of a deficit in serotonin transporter neurons. In other words, some patients don't have the transport system needed to keep serotonin at sufficient levels. 

New research is looking ways to stem the loss of serotonin and find a different network of neurons and neurotransmitters to treat some forms of dementia that have their roots in how serotonin levels are managed by the brain. Scientists at Johns Hopkins University have published a study in the journal Neurobiology of Disease that looked at MRI scans to investigate whether the lower serotonin factor is a player in the cause of Alzheimer's or if the disease is the cause of lower levels

Gwenn Smith, professor of psychiatry and behavioral sciences and director of geriatric psychiatry and neuropsychiatry at the School of Medicine at JHU and an author of the study, explained, "Now that we have more evidence that serotonin is a chemical that appears affected early in cognitive decline, we suspect that increasing serotonin function in the brain could prevent memory loss from getting worse and slow disease progression."

It's fairly a fairly standard option to treat some forms of cognitive decline or Alzheimer's with medications in the SSRI class of antidepressants, but there hasn't been much real success according to Smith. SSRIs work by blocking the brain's reuptake of serotonin, and they do that by binding to the transporters. Because patients with AD don't have as many of the serotonin transporter genes, the medications cannot target these proteins and work as they should.

In the study conducted by Smith's team 28 participants with mild cognitive impairment, (often an early sign of AD) with 28 healthy individuals as a control group. Cognitive impairment was determined by testing participants with the California Verbal Learning Test, which requires that subjects recall groups of words accurately after reading them. The average age of the study volunteers was 66, and almost half (45%) were women. 

MRI scans and PET scans were conducted on every participant to measure brain structure and serotonin transporter activity.  This was possible because the PET scans detected a radioactive carbon that binds to serotonin transporters. The carbon was attached to a chemical similar in molecular structure to an SSRI antidepressant, but that was not powerful enough to have any effect. The radioactivity that was detected allowed the researchers to tally up the serotonin transporters. 

Those in the study with mild cognitive impairment had up to 38 percent less of the serotonin transporter detected in their brains compared to the healthy control group. In fact, each participant in the impaired group was age matched to a healthy counterpart, and there wasn't one case where the impaired patient had more serotonin transporters than their neurotypical study partner. 

There were also differences in memory ability, with the cognitively impaired group performing at significantly lower levels on memory tests and tasks that required remembering shapes and letters. The study was built on prior research by co-author Alena Savonenko that showed a correlation between a loss of serotonin transporters and an increase of amyloid protein clumps in lab mice. The video explains more about the work and what it could mean for future research into serotonin transport and dementia.

Sources: Johns Hopkins, UPI, Neurobiology of Disease