Therapies that augment neurogenesis, the growth of new neurons in the brain, may eventually lead to treatments for neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. A recent scientific report described the latest findings in neurogenesis research.
We are capable of thinking, storing memories, and carrying out complex behaviours because of an intricate network of billions of neurons in our brains. Unfortunately, aging, brain injury, or harmful genetic mutations can all cause neurons to be lost. This can lead to devastating neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease.
Scientists now know that small numbers of new neurons are continuously produced in the adult brain. This process, called neurogenesis, normally does not occur fast enough to compensate for the loss of neurons in neurodegenerative diseases. However, recent research points to future therapies that may, one day, augment neurogenesis and help to treat these devastating diseases. A recent article in the scientific journal Translational Neurodegeneration described some of the latest findings in neurogenesis research.
The Origin of New Neurons
All new neurons in the adult brain start off as neural stem cells. These special cells are capable of transforming into neurons and other cell types. The rate of neurogenesis is largely determined by how quickly neural stem cells develop into neurons and how rapidly neural stem cells can regenerate their numbers.
The adult brain contains a relatively small number of neural stem cells. Many laboratory studies have tried injecting additional neural stem cells into the brains of mouse or rat models of Alzheimer’s and Parkinson’s disease, with promising increases in neurogenesis and decreases in disease severity. Surprisingly, only part of the effect appears to be due to injected stem cells transforming into new neurons. Instead, the new stem cells seem to stimulate neural stem cells that were already in the brain. In fact, even injecting other types of stem cells increased neurogenesis. Because of this, there are seven ongoing clinical trials in which mesenchymal stem cells, which are much easier to obtain than neural stem cells, are being injected into Alzheimer’s disease patients. Most of these studies chose to inject the stem cells intravenously, which is much safer than injecting directly into the brain.
Biological Factors that Affect Neurogenesis
Hormones are chemical messengers that are produced in glands and then distributed throughout the body via the bloodstream. They regulate many bodily functions, ranging from fertility to hunger. Sex hormones, such as estrogen and testosterone, appear to stimulate the generation of new neurons. Hormones that lessen appetite, such as leptin, also appear to increase neurogenesis. In contrast, stress hormones, such as cortisol, slow down the generation of new neurons.
Neurotransmitters are signaling molecules that are required for communication between adjacent neurons. The neurotransmitters serotonin and dopamine, which regulate mood and behavior, both promote neurogenesis in rodents. A recent clinical trial used gene therapy to increase dopamine levels in Parkinson’s disease patients, successfully decreasing disease severity. Unfortunately, this procedure required injections directly into the brain, with a high risk of dangerous side effects.
Cytokines are a broad collection of signalling proteins released by many types of cells within the body. Infection or brain injury causes the release of types of cytokines that trigger inflammation. These pro-inflammatory cytokines, along with brain inflammation, slow neurogenesis in rodents. In contrast, other cytokines that act to oppose inflammation increase the rate of neurogenesis.
Anti-inflammatory drugs increased neurogenesis and spatial learning in adult mice and were able to restore the normal rate of neurogenesis in rodents with brain inflammation. A clinical study found that the long-term use of anti-inflammatory drugs, like ibuprofen, decreased the risk of the elderly developing Alzheimer’s disease. However, more studies are required to confirm the effect, and to better understand potential side-effects of long-term treatment with anti-inflammatory drugs.
Neurotrophic Growth Factors
Neurotrophic growth factors are another type of signalling molecules that directly stimulate the growth of neurons. Patients with Alzheimer’s and Parkinson’s disease have lower levels of these neurotrophic growth factors in their brain neurons. Unfortunately, growth factors are large molecules that have trouble crossing from the bloodstream into the brain. However, the injection of growth factors directly into the brain has shown promising effects in rodents and monkey models of Parkinson’s disease, increasing neurogenesis and even improving cognitive function. This approach has also been tested in a small number of Alzheimer’s disease patients, with positive effects on disease severity. Unfortunately, some patients suffered side effects such as pain and decreased appetite, and injecting directly into the brain is somewhat risky.
Can Changes in Behaviour Affect Neurogenesis?
Exercise has many well-known health benefits, and it also appears to increase neurogenesis. For example, exercise in mice increased neurogenesis, as well as memory and learning. Furthermore, in a clinical study performed on healthy adolescents, high-intensity exercise increased the levels of neurotrophic growth factors and memory.
Diet also appears to have a substantial effect on neurogenesis. For example, feeding rats and mice a diet high in saturated fat and sugar decreased neurogenesis and impaired memory and learning. In contrast, supplementing rodent diets with poly-unsaturated fatty acids (PUFAs) or polyphenols such as resveratrol and curcumin increased neurogenesis and cognitive function. And diets that dramatically decreased overall caloric intake led to increased neurogenesis and improved learning and memory.
A Healthy Diet and Exercise May Stimulate Neurogenesis Naturally
The rate of neurogenesis is decreased in the early stages of Alzheimer’s and Parkinson’s disease, as well as in other types of aging-associated dementias. This suggests that therapeutic approaches increasing neurogenesis may be effective in treating these diseases. Many animal studies suggest that hormones, neurotransmitters and other substances naturally produced in the body could be used to stimulate neurogenesis, but clinical studies still need to be done to determine if these methods are effective and safe for human patients. In the meantime, researchers suggest that a healthy diet and exercise could potentially stimulate neurogenesis in a wholly natural way.
Written by Bryan Hughes, PhD
Reference: Shohayeb, B., Diab, M., Ahmed, M. & Ng, D. C. H. Factors that influence adult neurogenesis as potential therapy. Translational Neurodegeneration 7, 4 (2018).