Noggin and BDNF Promotes Neurogenesis

Notes...

The BDNF Response to Health and Trauma

BDNF (brain-derived neurotrophic factor) is one of the most potent healing compounds in your brain. Adequate BDNF is needed for brain plasticity, cognitive intelligence, optimal learning, positive mood, etc. In other words BDNF is your brain rejuvenation compound. BDNF can prevent and treat Alzheimer’s disease. BDNF is even active outside your brain wherein it helps your muscles burn fat! A lack of BDNF sets the stage for addictive behavior, including compulsive overeating. Those with the lowest levels of BDNF have the worst depression.

You can activate BDNF with aerobic exercise, even consistent moderate aerobics. Aerobics in older adults has been shown to stop brain shrinkage and boost BDNF while preventing depression. There are many nutrients that facilitate the production and release of BDNF (DHA, pantethine, acetyl-l-carnitine, zinc, blueberries, curcumin, niacin, DHEA, and likely many others). Nutrients work very well to maintain BDNF levels in the face of high levels of stress, as clicking on any of the study links in the previous sentence will explain to you. In order to properly activate BDNF it also requires proper function of thyroid hormone – an issue that is problematic in many people with depression.

BDNF production in your brain occurs within glial cells (astrocytes). It is very important to understand that BDNF production can be activated by multiple signals coming into the glial cells, not just one type of input. In other words, we have glial cell activation in response to healthy behaviors like exercise and good nutrition, part of the ongoing process of keeping your brain rejuvenated and in tip-top working condition. In animal experiments following stroke, voluntary exercise helps produce high levels of BDNF and nerve regeneration whereas forced exercise does not.

BDNF is also activated during times of brain injury, so as to repair the injury. Nerve cells do not split and divide like other cells in your body. Rather, nerve cells must either fix themselves or have a strategy to develop new nerve growth, and both processes require BDNF.
full article here: http://www.newswithviews.com/Richards/byron207.htm

full article here: http://www.jneurosci.org/content/24/9/2133.full

Adenovirally Expressed Noggin and Brain-Derived Neurotrophic Factor Cooperate to Induce New Medium Spiny Neurons from Resident Progenitor Cells in the Adult Striatal Ventricular Zone

Eva Chmielnicki,¹ Abdellatif Benraiss,¹ Aris N. Economides,² and Steven A. Goldman^1,3

¹Department of Neurology and Neuroscience, Cornell University Medical College, New York, New York 10021, ²Regeneron Pharmaceuticals, Inc., Tarrytown, New York 10591, and ³Department of Neurology, University of Rochester, Rochester, New York 14642

Abstract

Neurogenesis from endogenous progenitor cells in the adult forebrain ventricular wall may be induced by the local viral overexpression of cognate neuronal differentiation agents, in particular BDNF. Here, we show that the overexpression of noggin, by acting to inhibit glial differentiation by subependymal progenitor cells, can potentiate adenoviral BDNF-mediated recruitment of new neurons to the adult rat neostriatum. The new neurons survive at least 2 months after their genesis in the subependymal zone and are recruited primarily as GABAergic DARPP-32⁺ medium spiny neurons in the caudate-putamen. The new medium spiny neurons successfully project to the globus pallidus, their usual developmental target, extending processes over several millimeters of the normal adult striatum. Thus, concurrent suppression of subependymal glial differentiation and promotion of neuronal differentiation can mobilize endogenous subependymal progenitor cells to achieve substantial neuronal addition to otherwise non-neurogenic regions of the adult brain.

Administration of Noggin and BDNF to Promote Neurogenesis

Invention:

• Co-administration of two proteins - noggin and BDNF -- directly or via gene therapy, to promote the brain's own ability to produce new neurons
• Potential treatment for: depression, neurogenerative diseases (e.g. Alzheimer's); traumatic injury, stroke.

Level of Development: Efficacy in mouse model of Huntington's Disease.
The investigators found that neuronal production from adult ventricular zone (VZ) progenitor cells may be synergistically promoted by administration of, or concurrent overexpression of, noggin and a neurotrophic factor.
Noggin suppresses glial differentiation -- its administration prevents the brain's neural stem cells from being diverted away from becoming neurons.
Neurotrophins, such as brain-derived nerve growth factor (BDNF) promote the differentiation of new neurons from VZ progenitor cells, as is disclosed in this invention from the same lab.

Additional Information (publications, web sites, and patent links)

• Chmielnicki E et al. (2004) Adenovirally expressed noggin and brain-derived neurotrophic factor cooperate to induce new medium spiny neurons from resident progenitor cells in the adult striatal ventricular zone. J Neurosci. 24(9):2133-42.
• Cho SR, Benraiss A, et al (2007) Induction of neostriatal neurogenesis slows disease progression in a transgenic murine model of Huntington disease. J Clin Invest. 2007 Sep 20; [Epub ahead of print]
• Goldman, SA (2004) Directed mobilization of endogenous neural progenitor cells: the intersection of stem cell biology and gene therapy. Curr Opin Mol Ther. 6(5):466-72. Review.
• Patent: 7,576,065;

Sources
http://www.newswithviews.com/Richards/byron207.htm

Related Posts
Royal Jelly for Neurogenesis