Molecular Basis


*The following information may require a background in neuroscience for a complete understanding.

LOCAL ENVIRONMENTS

There are many aspects of the control of a process like  neurogenesis that remain to be fully understood by researchers in the field. One such area of obscurity is the mechanism that restricts neurogenesis to very specific brain regions. Like many parts of development, local environments are involved in guiding undifferentiated precursor cells towards their ultimate fate in the brain. Researchers have identified many molecules involved in progenitor differentiation, the most recent being endothelial cells, complement factors, and microglia.  Future research intends to reveal these mechanisms, as well as understand how the diversity of newborn neurons steers adult neurogenesis. (Ninkovic, J. and Gotz, M. 2007)


GENETIC CONTROL

Hippocampal Neurogenesis

In order to study the genetics behind neurogenesis, researchers have turned to mice as an animal model for the process in humans. Mice can be bred to generate many different strains with different genetic makeups. Several researchers have discovered differences in the proliferation and survival of neurons in the dentate gyrus between several mouse strains. Staining techniques enable researchers to observe the differences in all aspects of hippocampal neurogenesis – proliferation, survival, differentiation, overall volume, and total cell numbers. These findings indicate that, despite the significant role of environment on neurogenesis, genetics have an equally important function in the process. It remains to be seen exactly which molecules govern the genetics behind hippocampal neurogenesis, but this is certainly a topic under investigation by today’s scientists. (Pozniak, C. D. and Pleasure, S. J. 2006)


MICROENVIRONMENT MOLECULES

GABA

GABA is a major inhibitory neurotransmitter in the adult brain. It is responsible for activating GABAA receptors, which cause excitation of mature neurons. In the embryo, this neurotransmitter depolarizes neural progenitors. In the adult brain, it depolarizes immature neurons. Recent research indicates that GABA may play a role in the regulation of adult neurogenesis. The brain may reorganize its structure based on the areas that receive the most activity – this characteristic of the brain is known as neuroplasticity.  There is an increasing amount of evidence suggesting that the different steps of neurogenesis are differentially regulated by physiological and pathological stimuli, including an enriched environment, stress, learning, and seizures.

The abundance of research into GABA-controlled neurogenesis mechanisms may lead neuroscience towards promising treatments to repair the mature central nervous system after injury or neurological disease. In order to further these types of investigations, scientists must devise a way to study neurogenesis and its regulation in vivo. (Ge et al. 2006)

VGF

The role of neurogenesis in depression is a hot topic in neuroscience. New neurons themselves do not directly affect depression, but rather, these cells alter the way antidepressant treatments are received by the brain. For example, brain-derived neurotrophic factor (BDNF) is increased in the hippocampus by antidepressant treatments to exert antidepressant-like effects.  Previous studies with BDNF have defined its role in hippocampal neuronal development and plasticity. Further research with this molecule is done to identify the gene that are downstream of its control, including the neuropeptide VGF.

In animal models of depression, researchers have seen that VGF is decreased in the hippocampus after both the learned helplessness and forced swim test (FST). However, when VGF is infused into the hippocampus of mice prior to their turn in FST, their signs of depression were greatly reduced. These behaviors, in response to varying levels of VGF in the hippocampus, are indicative of  an antidepressant-like function for VGF. In fact, further investigation with VGF has revealed that VGF, working downstream from BDNF, may exert its antidepressant-like effects by enhancing neurogenesis in the hippocampus. (Thakker-Varia et al. 2007)

Fibroblast Grown Factor-2 (FGF-2)

Current neuroscientists understand development of the mammalian brain in terms of neuronal generation from multipotent neural stem cells. However, more recent research has shed light on the claim that neurogenesis may also be controlled throughout adult life by exposure to FGF-2.  A comparison of cells from the hippocampus and the neocortex showed a clear program of proliferation. A more thorough analysis of these cells indicated that, although these precursors exist, their differentiation requires the presence of FGF-2. Researchers have also found evidence of these neural precursors in the optic nerve, suggesting a diverse function of these cells. (Palmer et al. 1999)

Photos:

GABA: http://sites.lafayette.edu/neur401-sp10/files/2010/04/GABA.gif

Mice: http://www.dogbreedinfo.com/images19/MiceAdorableSiamese2.JPG

Leave a Reply