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1 Running head: Levi-Montalcini and NGF 1 Rita Levi-Montalcini and Nerve Growth Factor Dani Harrison George Mason University

2 Levi-Montalcini and NGF 2 The Discovery of Neurotrophic Growth Factors Rita Levi-Montalcini was born in 1909 in Turin, Italy. Her father was an accomplished engineer and her mother was an artist. Levi-Montalcini had three siblings that influenced her early life: her twin sister Paolo, her older brother Gino, and older sister Anna. Levi-Montalcini found a passion for literature, influenced by Anna, and intended to become a writer. Although her parents instilled in us their high appreciation of intellectual pursuit ( Rita Levi-Montalcini, n.d., para. 2), she was discouraged from a professional career by her father. He held that women should put the duties of the wife and mother before all else. Levi-Montalcini said her family was highly supportive, and this atmosphere gave her confidence to enter into the, at the time, male dominated medical field. She asked her father for permission to enroll in a university when she realized that the homemaker lifestyle was not for her. She decided to pursue medicine after a close family friend passed away to stomach cancer. She graduated from the University of Turin Medical School in 1936 with a degree in medicine and surgery. She then was trying to decide on a specialty program between neurology and psychiatry, but precluding events of World War II interrupted her further education. Benito Mussolini signed a number of laws that prevented non-aryan Italian citizens. This forced Levi-Montalcini, of Jewish-Italian heritage, to abandon her position as a guest at Brussel s Institute of Neuology. She returned to her family in Turin, and built a research unit in her bedroom, where she began developing her nerve theory based on research by Viktor Hamburger. Her theory was based on the hypothesis that immature nerve cells are programmed to die by apoptosis. Her family had to leave Turin a year after she returned because of bombing by the American forces. She relocated to Piemonte

Levi-Montalcini found a passion for literature, influenced by Anna, and intended to become a writer.

3 Levi-Montalcini and NGF 3 and continued her research, until the German occupation of Italy two years later caused her to flee to Florence. She worked as a physician to wounded war refugees until the end of the war, after which she returned to Turin. She was then invited by Hamburger to work with him at the Washington University in St. Louis, Missouri. She planned to stay a year, but stayed for over thirty ( Rita Levi-Montalcini, n.d.). A paper Hamburger published in 1934 inspired the research Levi-Montalcini was conducting during the war. He had found that removing wing buds on chick embryos influenced the development of the CNS (Jiang, 2010). This led to the hypothesis that target tissues chemically signal relevant neurons. Additionally, the chemical signal produced played a role in the competitive nature of nerve growth, survival, and death. A former student of Hamburger had removed a wing bud from a chick embryo and replaced it with a tumor from a mouse. Levi-Montalcini and Hamburger were then surprised that the mouse tumor had been innervated more fully than the original limb would be otherwise. Specifically, sensory and sympathetic ganglia were stimulated. Levi- Montalcini and Hamburger found that the tumor secreted a soluble factor, at a higher amount than the limb naturally, that stimulated the nerve growth and survival. Levi- Montalcini was able to separate this soluble factor and identify it as a protein. She called it nerve growth factor due to its abilities (Purves et al., 2001). The role and production of NGF was further researched. Mice that received injections of NGF had larger sympathetic ganglia, and inversely, mice injected with an NGF antiserum were found to be missing most NGF dependent neurons (Levi-Montalcini & Angeletti, 1968, p. 536). Early on, NGF was looked into as a chemotropic molecule, but it was found that NGF was only secreted after the NGF-sensitive nerve cell s axon

Louis, Missouri. She planned to stay a year, but stayed for over thirty ( Rita Levi-Montalcini, n.d.).

4 Levi-Montalcini and NGF 4 had reached it s target location, not supporting the notion that it guided neuronal growth paths. What it does is supports the growth of neurites after the nerve reaches the target tissue, and sustains the axonal branches and dendrites after they form. Additionally, the amount of NGF secreted by the target tissue is quantitatively and positively linked to the density of the innervated neurites (Purves et al., 2001). NGF was the first neurotrophic factor identified. Because it only affected the growth of sensory and sympathetic nerves, Levi-Montalcini and her fellow researchers concluded that other neurotrophic chemicals accomplished similar development in other nerve types. Another interesting neurotrophic factor is Brain-Derived Neurotrophic Factor (BDNF). This chemical is most abundant in adult human s cerebral cortex (Kalat, 2007, p. 129). BDNF also promotes nerve growth and sustenance, and assists in neural plasticity. There has been investigation into BDNF production in late age memory recall (p. 393). Additionally, difficulty in producing BDNF has been a newer area of research in depression and individuals at-risk for suicide (Dwivedi, 2013). Levi-Montalcini s contributions to the discovery of NGF earned her the Nobel Prize in Physiology or Medicine in 1986, alongside her longtime research partner, Stanley Cohen. There has been some debate as to why Viktor Hamburger was not awarded the prize as well, considering his involvement. Nonetheless, the discovery of neurotrophic factors has yielded a large field of research in nerve physiology and development that can help developmental nerve defects as the technology and knowledge continues to improve.

Additionally, the amount of NGF secreted by the target tissue is quantitatively and positively linked to the density of the innervated neurites (Purves et al., 2001).

5 Levi-Montalcini and NGF 5 References Dwivedi, Y. (2013). Involvement of brain-derived neurotrophic factor in late-life depression. The American Journal of Geriatric Medicine, 21(5), doi: Jiang, L. (2010). The effects of wing bud extirpation on the development of the central nervous system in chick embryos by Viktor Hamburger. Embryo Project Encyclopedia, n.p. Retrieved from Kalat, J. W. (2007). Biological Psychology (9th ed.). K. Bomont (Ed.). Belmont, CA: Thomson Wadsworth. Levi-Montalcini, R., & Angeletti, P. U. (1968). Nerve growth factor. Physiological Reviews, 48(3), Purves, D., Augustine, G. J., Fitzpatrick, D., Katz, L. C., LaMantia, S. A., McNamara, J. O., & Williams, S. M. (Eds.). (2001). Molecular basis of trophic interactions. In Neuroscience (2nd ed.). Retrieved from: "Rita Levi-Montalcini - Biographical" (n.d.). Retrieved from

Embryo Project Encyclopedia, n.p. Retrieved from http://embryo.asu.edu/pages/effects-wing-budextirpation-development-central-nervous-system-chick-embryos-viktorhamburger Kalat, J. W. (2007).

Neurotrophic factors and Their receptors

Neurotrophic factors and Their receptors Huang Shu-Hong Institute of neurobiology 1 For decades, scientists believed that brain cells of the central nervous system could not regrow following damage due