Stem cells may be the key to memory, depression

13 December 2016

Modern life can be stressful, and recent research has shown that on-going stress can damage the brain and trigger depression. Depression and anxiety are the country’s leading cause of disability, affecting three million Australian adults each year. Queensland researchers digging deep into the brain to understand why, have identified stem cells that could not only help us to become more resilient to the pressures of modern life, but improve our memory into old age. Researchers at the Queensland Brain Institute and Brisbane’s Mater Research Institute have identified and isolated the stem cells responsible for generating new neurons in the hippocampus, part of the brain that regulates mood and memory. “It’s exciting. We actually have biomarkers to purify stem cells that were not available up until now,” said neurobiologist Dr Dhanisha Jhaveri, “and that has the potential to really improve our understanding of generating new nerve cells. It’s also given our research the impetus to go further, and look at what we can do with these newly discovered stem cells, to treat not only depression, but memory loss in ageing.” The focus of all this research is the hippocampus, an area deep within the brain that plays a role not only in depression, but in memory-associated illnesses such as Alzheimer's and dementia. Dr Jhaveri is a senior research fellow working with neuroscientists and clinicians at the Queensland Brain Institute and the Mater Research Institute, both part of the wider Brisbane Diamantina Health Partners collaboration. Working with the hippocampus in animal models, Dr Jhaveri’s team has identified dormant stem cells in adult brains that can be activated to produce new-born neurons. “We are trying to understand what role these stem cells and new-born neurons play in the etiology of depression.” Prolonged stress has been shown to damage the hippocampus and impede the production of new born neurons. Even if the stem cells are still producing new-born neurons, stress can change their physical shape. The hippocampus can even shrink in some patients with chronic depression who don’t respond to anti-depressants. “There’s actually a correlation between the volume of the hippocampus, and depression that’s not being treated or can’t be treated with antidepressant treatments,” said Dr Jhaveri. If the neurons are damaged or aren’t being made, it can dramatically affect mood and memory. “And that’s important to know because we are what we are because of the neuronal activity in our brains.” While stress is a major risk factor associated with depression, the type of stress that appears to damage the brain and trigger depression isn’t short term stress. “Acute stress in fact could be very beneficial, because that's where the whole system gets into the alert mode and where are able to work much more efficiently,” said Dr Jhaveri. “What we're talking about is here is a maladaptive stress, where there is a stress over a prolonged period of time that can lead to depression and anxiety.” Depression is the leading cause of disability worldwide, affecting around a million Australian adults each year. Another two million Australians experience persistent anxiety. One of the problems psychiatrists face in treating depression, is that a third of patients don’t respond to antidepressants. That could be because chronic stress has already damaged the hippocampus. “If a third of those people aren’t responding to the current medications, you can imagine the burden that brings to society,” said Dr Jhaveri. “What we’re trying to understand here is the etiology of depression. It’s that long-term, chronic stress that we’re concerned with here because it’s one of the major precipitating factors for anxiety and depression that affects so many Australians.” Dr Jhaveri’s team hopes that by pinpointing the biological mechanisms and targets for psychological illnesses such as depression, they can find safer and more effective treatments. For instance, if dormant stem cells in the hippocampus can be activated to produce more neurons, especially in adults, some of that damage caused by long-term stress can theoretically be repaired. “So we are trying to push forward and identify novel targets on the stem cells that could be targeted by pharmacological agents,” she said. Some of those treatments might involve new technologies. “For instance, if we can understand the biology of these stem cells, perhaps we can combine that with some sort of nanotechnology where we deliver compounds in a very selective fashion that will activate the stem cells to increase the production of new neurons. That, potentially, might be one way of coming up with a novel anti-depressant that is not only fast acting, but also safe.” It’s early days. Working with animal models, the team has already identified the stem cells in the hippocampus and found a way to activate them in mice. The next step is to see if that model is similar in the human brain. “It's very exciting, and one can think of actually utilising some of the models and assays we’ve developed and using some of the libraries of drug compounds that are already available, to see if they work by screening those in our assays.” In other words, there’s also potential to repurposing existing drugs to see if they can target dormant stem cells in the brain of adults to treat not just depression, but halt or reverse memory loss. If that’s the case, then new treatments for depression might not be that far away.

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