Newly discovered compounds may reverse memory loss associated with depression and aging

  30 Apr 2019

Contrary to popular belief, memory loss isn’t exclusive to old age and neurodegenerative diseases like dementia. It’s also commonly seen in people experiencing emotional distress – especially in those who deal with chronic mental health conditions like depression and anxiety.

For example, a study which appeared last year in an issue of the journal Neurology found that individuals that exhibited perceptible symptoms of depression also were shown to have a substandard episodic memory – the kind of memory the remembers particular events.

Recently, researchers at Toronto’s Centre for Addiction and Mental Health in Canada (CAMH) have developed new therapeutic compounds which have shown promise in reversing memory loss that’s associated with depression and aging. In preclinical models (lab mice), not only did these compounds improve symptoms common in memory loss, but, also appeared to ‘fix’ or regenerate underlying brain mechanism impairments which cause poor memory.

“Currently, there are no medications to treat cognitive symptoms such as memory loss that occur in depression, other mental illnesses, and aging,” noted Dr. Etienne Sibille, the lead scientist on the study, and the Deputy Director of the Campbell Family Mental Health Research Institute at CAMH.

“What’s unique and promising about these findings, in the face of many failures in drug development for mental illness, is that the compounds are highly targeted to activate the impaired brain receptors that are causing memory loss”, Dr. Sibille added.

Dr. Sibille and his team have published the findings of their most recent study in the journal Molecular Neuropsychiatry.

During the initial stage of their research, Dr. Sibille and his team searched for and identified the disruptions occurring in brain cell receptors involved in the GABA neurotransmitter system. A large body scientific research suggests that dysfunctions in the brain’s GABA system are linked to mental health issues like depression and anxiety.

Next, the team showed that these specific disruptions likely caused mood and memory symptoms seen in depression and aging.

In the following phase of research, the scientists developed a series of benzodiazepine-like compounds that would bind to and activate the faulty receptors, and thus exert a therapeutic effect by ‘fixing’ the impairment, and thereby eliminate or improve memory loss symptoms.

Benzodiazepines are a class of anti-anxiety and sedative medications which also activate the brains GABA system. Unlike the compounds used Dr. Sibille’s research, benzodiazepines are not highly targeted.

Only 30 minutes after a single dose of these new compounds was administered to mice with stress-induced memory loss, the memory performance of the mice returned to normal levels. The experiment was reproduced over 15 times with the same results.

In a different experiment involving aged mice with memory defects, the memory defects were quickly reversed. After the compounds were administered, memory performance actually increased to 80 percent and reached levels seen in youth or early stages of adulthood.

Improvements lasted more than two months with daily treatment.

“We’ve shown that our molecules enter the brain, are safe, activate the target cells, and reverse the cognitive deficit of memory loss,” one of the researchers said.

“The aged cells regrew to appear the same as young brain cells, showing that our novel molecules can modify the brain in addition to improving symptoms,” says Dr. Sibille.

If proven successful, the applications for these new compounds are expansive. Currently, there’s an enormous lack of treatments available for cognitive impairments and deficits caused by mental illness and mood disorders. Furthermore, compounds like these could be used to help combat memory loss in Alzheimer’s disease as well.

In two years, Dr. Sibille and his team of scientists hope to begin testing the safety and effectiveness of these new compounds in clinical trials involving human participants.