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Laboratory for Neurogenesis and Stem Cell Research

Center for Brain Repair and Rehabilitation
Dept. of Clinical Neuroscience and Rehabilitation
Institute of Neuroscience and Physiology
University of Gothenburg

Team members

Anke Brederlau, MD, PhD, Research Associate
Christiana Cooper-Kuhn, PhD, Research Associate
Nina Hellström, PhD student
Åsa Persson, PhD student
Jenny Zhang, PhD student
Olle Lindberg, Masters student

Alumni

Andrew Naylor, PhD
Cecilia Bull, PhD

Research profile

The brain has classically been thought of as a structure with very limited regenerative capacity. However, substantial evidence has accumulated over the last decades that new neurons are generated from stem cells in the adult mammalian central nervous system.

During nervous system development, neurons and glial cells are generated from multipotent stem cells that have the capacity to proliferate and to reproduce themselves. These neural stem cells have been shown to be active in the central nervous system (CNS) of humans as well. New neurons are generated in discrete areas of the juvenile and adult brain where they are integrated into functional networks. The goal is to learn from this phenomenon in order to achieve optimal brain maturation, healthy brain aging as well as brain repair in neurological diseases and after injury.

Neurogenesis not a single event, but a prolonged development process sensitive to external influences. It is therefore not surprising that a multitude of stimuli has been described over the recent years, which appear to influence neurogenesis in the juvenile and adult brain. Among these are hormone, neurotransmitter, growth factors and other molecular signals that define and regulate the neurogenic niches in the brain. The laboratory is currently interested in several aspect of neurogenesis and stem cell research:

Enriched environment and physical activity as therapeutic stimulators of stem cell activity and brain repair
A remarkable positive effect on the generation of new neurons from stem cells has been described for peripheral and environmental signals. Especially, physical exercise and environmental stimulation are among the best neurogenic signals. These paradigms have become important factors in modern neurorehabilitation, but are still not understood in terms of molecular and cellular processes that lead to enhanced plasticity and functional recovery.

Influence of pathological environments on stem cells and their niche.
Acute brain lesion, such as trauma and stroke, and epilepsy appear to activate the neurogenic mechanisms, whereas chronic neurodegenerative conditions appear to suppress the ability to produce new neurons. It is still unclear, what triggers the different responses but it appears that stem cells and their progeny express receptors for numerous signaling molecules that are released in pathological situations. Moreover, accumulation of proteins Are stem cells especially vulnerable to extra- and intracellular protein aggregations alter stem cell behavior?

Common signals for neuroprotection, neuroplasticity and neurogenesis
Therapeutic progress after acute brain injury and stroke or during the progression of neurodegenerative disorders, such as Alzheimer’s disease, has to involve stimulation of several cellular mechanisms, that (1) minimize the damage to existing neurons, (2) stimulate the formation of new synaptic circuits and (3) help to replace lost neurons. Interestingly, quite a few trophic factors present a profile of protective, plasticity-enhancing, and progenitor-stimulating activity. Such “brain-anabolic” factors need to be further studied in animal models of neurodegeneration, in order to develop new plasticity-promoting drugs that could enhance rehabilitation therapy.

Vulnerability of stem cells in the immature brain
Although we assume that the immature brain is capable of more significant repair mechanisms compared to the adult brain, severe defects can be observed, if the postnatal stem cell pool and neurogenesis are impaired. For example, thyroid hormone deficiency or postnatal irradiation, as part of cancer treatment, can significantly alter the stem cell pool and produce long-lasting cognitive defects. It is important to study the response of the young brain to damaging conditions and its stem cell behavior in order to develop more specific treatment of injuries and diseases of the immature brain

Neural stem cells as precursors to cancer cells
Growth factor over-stimulation of stem cells can lead to the generation of tumor-like brain hyperplasias. Stem cells react remarkably similar to brain tumor cells, including uncontrolled proliferation, invasive migration and neoangiogenesis. In vivo and in vitro analysis can reveal how many properties attributed to cancer cells are actually stem cell properties. This will help to understand the earliest stages of tumorogenesis and may help developing more effective tools for the prevention and treatment of brain cancers.

Stem cells, biomaterials and structural brain repair
In this project, we explore the possibilities of combining stem cells with biomaterials. Engineered biopolymers provide novel surfaces, with which stem cells can interact. The potential application of this research reaches from bioreactor materials for in vitro expansion of stem cells to implantable carbon-nanofibers, which could provide an optimized matrix for stem cell migration and differentiation in the brain. This project is conducted in close collaboration with Chalmers University of Technology and Cellartis AB, Gothenburg.


 

Laboratory Director

Georg Kuhn

H. Georg Kuhn, Dr. rer. nat., Professor
Tel: +46 (0)31 786 3435
Fax: +46 (0)31 786 3401
E-mail: georg.kuhn@neuro.gu.se

Sidansvarig: Katinka Almrén|Sidan uppdaterades: 2011-12-17
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