Enhancing or maintaining adult neurogenesis has huge potential as a therapeutic target for neuron loss
It’s no great point of contention that the brain is by far the most complicated and intricate organ in the human body. In fact many would argue that it’s the most powerful computational device that our planet has ever seen. It allows us to do some incredible things, but not even the most sophisticated of machines is immune to the ravages of time. Age-related neuron loss and neurodegenerative diseases have become more pertinent as human life expectancy has increased.
But what if we were able to slow this seemingly inexorable trend? To hold the swinging pendulum at bay for a while? Neurogenesis in the adult vertebrate and human brain was first identified 25 years ago, and the dysregulation of adult neurogenesis plays an important role in the progression of disease. Enhancing or maintaining adult neurogenesis has huge potential as a therapeutic target for age- and disease- related neuron loss. Dr. Anthony Windebank and colleagues at the Mayo Clinic in Minnesota have been studying a new and potentially valuable therapeutic agent in the fight against neural degeneration.
Mechano Growth Factor – more than an exercise supplement?
Mechano Growth Factor is a splice variant of Insulin-like Growth Factor 1. IGF-1 is a protein synthesized primarily in the liver, and plays a crucial role in stimulating growth and development of cells across a variety of tissue types. As a close relative, MGF is mainly expressed in skeletal and heart muscle, and is able to stimulate the proliferation of muscle stem cells (satellite cells) to rapidly repair damage and promote muscle growth.
Growth factors of this type are at their highest levels around childhood and adolescence, with a steady decline throughout adulthood and old age. Concurrently, in our later years we experience increased susceptibility to a host of physical and neurological ailments, as our bodies become less effective at repairing themselves.
It has been long since established that MGF is typically expressed in muscle tissue. In fact one of the most common uses for MGF on the market today is as an exercise supplement for athletes and bodybuilders trying to increase muscle mass. However, in a recent study published in Molecular Brain, Dr Windebank et al demonstrated for the first time that MGF plays a role in preventing neuronal attrition and brain dysfunction in aging mice.
MGF in the brains of mice
In this study, transgenic mice were bred so as to constitutively overexpress MGF in the hippocampus and the subventricular zone of the brain – regions associated with neural development and differentiation (neurogenesis). Histological analysis confirmed that these transgenic specimens displayed an abnormally high concentration of BrdU, a synthetic marker for detecting proliferating cells in live tissues. This indicates increased cell proliferation and growth in the specific regions of the brain.
Another group of double transgenic mice was then bred to display conditional MGF expression when triggered by the presence of an activating agent added to their drinking water. Using this new population, researchers were able to study the long-term effects of enhanced neural MGF production when triggered at 1, 3 or 12 months old. Behavioral analysis and further histological assays were then conducted at 24 months.
With significantly higher levels of BrdU+ proliferative cells in the brain, the mice with MGF overexpression also displayed an enhanced resistance to age-related neural degeneration, as evidenced by their improved olfactory behavior. Mice with enhanced levels of neurogenesis displayed greater speed and higher success in cognitive tests.
“As the neural progenitor cell population becomes dysfunctional with age MGF is not able to induce mitogenic effects (Windebank et al 2017).”
An interesting finding was that the efficacy of MGF was highly age-dependent. The earlier that MGF overexpression was induced, the more dramatic the eventual proliferation of BrdU+ cells, and subsequent neurological improvement throughout adulthood. If MGF production was not stimulated by the time the mice were 12 months old, they displayed no significant histological or behavioral differences to the control group.
At present, the cellular site or the mechanisms of MGF are unknown, and further work is needed to explore the cellular and behavioral effects of MGF on neurogenesis. What this study does make clear however, is that Mechano Growth Factor could someday have therapeutic applications far beyond its current role as a simple muscle building steroid.