Pioneering mouse research provides breakthrough in the search for adult brain stem cells
Generating new cells in the brain that regulate core body functions has moved one step closer as a result of state-of-the-art research at one of the UK's flagship research centres at the University of Sheffield.
Researchers at the University’s Medical Research Council Centre for Developmental and Biomedical Genetics (CDBG) performed a painstaking analysis of the behaviour of different cells of the adult mouse hypothalamus - a part of the brain that contains a number of small nuclei with a variety of functions such as the control of body energy levels.
Unlike the vast majority of cells in the brain, one type of hypothalamic cell – the so-called alpha-tanycyte - was found to exhibit neural stem cell activity, meaning the cell can self-renew when exposed to a well-known signal, or can differentiate into multiple brain cell types.
This ground-breaking research could pave the way for the generation of new hypothalamic cells, and the challenge now is to find out how different stimuli from the tanycyte’s environoment affect its decision to give rise to new brain cells.
All of us are dependent upon our hypothalamic cells, which regulate core body activities, including feeding, sleep and water balance. Diet and obesity are known to affect the birth of new hypothalamic neurons, and the present study pinpoints a gatekeeper cell: alpha-tanycytes that are in close contact with the blood stream, and so may be able to directly sample levels of circulating metabolites, then decide whether to give rise to a new cell that alters the hard-wiring of the adult brain.
The University of Sheffield researchers’ identification of the alpha tanycyte as a stem cell in the adult hypothalamus means that scientists can potentially generate new cells that control basic body functions, and offers new prospects of finding new treatments for hypothalamic disorders – which can be triggered by eating disorders, genetic disorders, stress and trauma.
Professor Marysia Placzek from the University of Sheffield’s Department of Biomedical Science, who led the project, said: “We combined our knowledge of features of the embryonic brain, and state-of-the-art transgenic mice, to perform a series of rigorous tests that would show the presence of a hypothalamic neural stem cell.
“We found that, of many cells tested, one had the features of a neural stem cell. Fascinatingly, we found that its proliferation is controlled by a local signal that is already known to govern proliferation of other types of embryonic and adult stem cells. The challenge now is to find how everyday factors, such as diet, impact on this signal"
The research, published in the journal Nature Communication, shows that adult hypothalamic stem cells can be cultured indefinitely in vitro (in a test tube), providing a means to generate large numbers of hypothalamic cells, including nerve and glial cells.
Nerve cells in the hypothalamus control core body activities by passing electrical impulses along their lengths, leading to the release of chemical signals known as neurotransmitters and neurohormones at nerve endings, which may then stimulate or inhibit neighbouring cells, including hormone-releasing cells.
Glial cells of the hypothalamus regulate neurohormone release. Imbalances in the neurotransmitters and neurohormones released can lead to abnormal regulation of hormones, and so can affect many body systems, including those that regulate feeding patterns, sleeping patterns and water balance.
Observing these processes at the level of individual nerve cells and molecules is difficult in humans, because the brains of humans are so large, complex and relatively inaccessible.
However, the mouse hypothalamus has the same components as the human hypothalamus: the same cells, the same molecules and the same neurotransmitters and neurohormones.
By studying alpha-tanycytes activity in mice it is possible to understand the same processes in the adult brain.
Professor Placzek added: “The ability to follow adult cells in time and space is proving to be a remarkably powerful in vivo system for adult cell activity. Over the last 10 years these type of research have helped us to understand how the nervous system is built and how alterations in this construction process may cause neurological and psychiatric diseases.
“Our study provides a starting point for how hypothalamic re-construction in the adult may impact on disorders that affect the brain’s ability to control the endocrine system.”
Medical Research Council Centre for Developmental and Biomedical Genetics
The University of Sheffield
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