Professor Rita Levi-Montalcini overleden, grondlegster van PEA en inspirator van PeaPure en een PEA-houdend product

Montalcini explored PEA Professor dr. Rita Levi-Montalcini is op 103-jarige leeftijd op zondag 30 december 2012 overleden. Een grootse vrouw die tot op zeer hoge leeftijd actief was, zowel als senator en als medisch wetenschapper.

Zij heeft haar leven op een bijzondere wijze geleefd, en op vele gebieden bijgedragen tot doorbraken in de geneeskunde. Haar briljante werk rond de oorlog met kippen-eieren leidde tot de ontdekking van de zenuwgroeifactoren.

Via haar kennis van de zenuwgroeifactor NGF beschreef ze in 1993 als eerste wetenschapper de bijzondere waarde van palmitoylethanolamide, een lichaamseigen pijnstiler die ontstekingscellen tot rust brengt.

Ze werkte door tijdens de Nazi-periode en ontdekte in haar eigen keuken, die ze omgebouwd had tot researchlaboratorium veel aspecten die uiteindelijk leidden tot de identificatie van de zenuwgroeifactor NGF. Wetenschap en grenzen verleggen binnen die wetenschap was haar passie. Ze broedde zo veel problemen uit tot werkzame hypotheses en bruikbare behandelingen: “You’ve been thinking about something without willing to for a long time, then, all of a sudden, the problem is opened to you in a flash and you suddenly see the answer.”

Het is uitermate zeldzaam dat iemand op de leeftijd van 102 jaar nog als wetenschappelijk auteur van een artikel optreedt, maar dat was Rita ten voeten uit. [1] Haar eerste artikel in pubmed dateerde van 1947; haar laatste dus van 2012. [2] Ze was wars van richtlijnen en een echte wetenschapkunstenares, in haar eigen woorden:

I’ve never been able to keep a log. Everything in me is imagination, intuition. Nothing is scientific. I am not a scientist, I’m an artist of science.

Palmitoylethanolamide; doorbraak in pijnbehandeling

Haar werk met palmitoylethanolamide in 1993 en de jaren daarop is een voorbeeld dat minder mensen goed kennen. [3] Maar ook hier was het duidelijk dat ze licht zag daar waar andere wetenschappers de feiten wel kenden, maar de samenhang niet doorzagen.

Palmitoylethanolamide was al bekend als ontstekingsremmend en pijnstillend lichaamseigen molecuul, maar het duurde van 1957 tot 1993 voordat men precies begreep waarom deze stof een zo belangrijke rol speelde. Zij ontdekte dat palmitoylethanolamide de ontstekingscellen bij chronische ontstekingen en pijnsyndromen tot rust kon brengen, en dat die stof een in ons lichaam ingebouwde geneeskrachtige stof was.

Zij was het ook die de geneeskunde de ogen opende voor de belangrijke rol die de mestcel, een ontstekingscel, speelt bij veel ziektebeelden. [4] [5] Zo beklemtoonde ze dat de mestcel zelf ook NGF produceert, en dat die productie leidt tot extra pathologie, in de vorm van een waterval van ontstekingsreacties. [6] Palmitoylethanolamide is de natuurlijke rem op die waterval. Het belang van die ontdekking is ook zeer recent weer beklemtoond door een van haar medewerkers. [7] Zelfs pijnen en zenuwstoornissen door chemotherapie hangen samen met deze overactieve mestcel en ook daar kan palmitoylethanolamide een belangrijke normaliserende rol spelen. [8]

Zo blijkt haar werk tot op heden actueel en draagt het vruchten.

We hebben het grote voorrecht gekend om deze ontdekking van Rita Levi-Montalcini breed in de kliniek bekend te mogen maken, zowel in Nederland als in de Engels-talige wetenschappelijke wereld. [9] Zo hebben we een stukje van haar gedachtengoed ook verder mogen ontwikkelen. Helaas is het er niet meer van gekomen deze bijzondere vrouw te mogen ontmoeten.

Zeer recent nog ontving Rita Levi-Montalcini regelmatig wetenschappers uit andere landen. Ze bleek tot op hoge leeftijd een bijzonder heldere geest te hebben.[10] [11]

We zullen haar met dankbaarheid gedenken en het door haar geinspireerde werk verder voortzetten. Ze deed het voor de wetenschap en voor de patienten.

Nobelprijs aankondiging Levi-Montalcini

In 1986 ontving zij, samen met Stanley Cohen, de Nobelprijs voor geneeskunde welke als volgt werd aangekondigd:

“The Nobel Prize in Physiology or Medicine is awarded for discoveries which are of fundamental importance for our understanding of the mechanisms which regulate cell and organ growth. The pattern of cellular growth has long been known, but it is the Italian developmental biologist Rita Levi-Montalcini and the American biochemist Stanley Cohen with their discovery of nerve growth factor (NGF) and epidermal growth factor (EGF), respectively, who could show how the growth and differentiation of a cell is regulated.

NGF and EGF were the first of many growth-regulating signal substances to be discovered and characterized. The discovery of NGF and EGF has opened new fields of widespread importance to basic science. As a direct consequence we may increase our understanding of many disease states such as developmental malformations, degenerative changes in senile dementia, delayed wound healing and tumour diseases. The characterization of these growth factors is therefore expected, in the near future, to result in the development of new therapeutic agents and improved treatment in various clinical diseases.”

Het volgende karakteriseert deze bijzondere vrouw, een observatie door een leerling:

Kruising tussen Maria Callas en Marie Curie

When viewed from inside Rita’s lab, there was also a sense of drama, style, and costume. Rita’s attire consisted of tailored dresses, designer jewelry, patterned hose and high-heeled shoes — the Queen of Italy in a lab coat.

While I was preparing to leave Washington University to accept a faculty position elsewhere, Johns Hopkins, then Chair of the Department of Biology, asked me what it was like to “ride the Levi-Montalcini roller-coaster.” I replied, “Overall, it was good ride. But it sometimes felt like working for a combination of Marie Curie and Maria Callas.”

When Johns asked me if he could share my anecdote, I replied “Yes, but you need not cite the source.” Actually, I suspect that Rita, most of all, enjoyed the “Rita Stories” told by colleagues around the world.

These tales often related over-the-top behavior, but were relished anecdotes about an honored colleague, not derisive comments about a scientific prima donna. Her hosts during lecture visits seemed to enjoy rolling out the red carpet, a chance to participate in a bit of scientific theater. It’s not everyday you are visited by the Queen of Italy.

Bron: In the trenches with Viktor Hamburger and Rita Levi-Montalcini (1965-1974) – One student’s perspective Provine, R.R. International journal of developmental neuroscience, Volume: 19, Issue: 2 (April 2001), pp: 143 – 149

Een deel van haar schrifturen

Levi-Montalcini, R. and E. Sacerdote. “Formazione di fibrille reticolari e collagene in colture di epiteli e di elementi miocardici.” Monitore Zoologico Italiano. 47 (1936): 309-18. Visintini, F. and R. Levi-Montalcini. “Relazione tra differenziazione strutturale e funzionale dei centri e delle vie nervosa nell-embrione di pollo.” Archives Suisses de Neurologie et de Psychiatrie. 43 (1939): 1-45. Levi-Montalcini, R. “Origine ed evoluzione del nucleo accessorio del nervo abducente nell’embrione di pollo.” Acta (Pontificia Accademia delle scienze). 6 (1942): 335-45. Levi-Montalcini, R. and G. Levi. “Recherches quantitatives sur la marche du processus de différenciation des neurons dans les ganglions spinaux de l’embryon de Poulet.” Archives de Biologie. 54 (1943): 189-206. Levi-Montalcini, R. and G. Levi. “Correlazioni nello sviluppo tra varie parti del sistema nervosa. I. Consequenze della demolizione dell’abbozzo di un arto sui centri nervosi nell’embrione di pollo.” Commentationes (Pontificia Accademia delle scienze). 8 (1944): 527-68. Levi-Montalcini, R. “Regressione secondaria del ganglio ciliare dopo asportazione della vesicola mesencefalica in embrione di pollo.” Rendiconti (Accademia nazionale dei Lincei). 3 (1947): 144-6. Levi-Montalcini, R. “The development to the acoustico-vestibular centers in the chick embryo in the absence of the afferent root fibers and of descending fiber tracts.” Journal of Comparative Neurology. 91, no. 2 (1949): 209-41. Hamburger, V. and R. Levi-Montalcini. “Proliferation, Differentiation and Degeneration in the Spinal Ganglia of the chick Embryo under Normal and Experimental Conditions.” Journal of Experimental Zoology. 111 (1949): 457-502. Hamburger, V. and R. Levi-Montalcini. “Some aspects of neuro-embryology.” In: Genetic Neurology, edited by Paul Weiss, 128-60. Chicago: University of Chicago Press, 1950. Levi-Montalcini, R. and V. Hamburger V. “Selective growth stimulating effects of mouse sarcoma on the sensory and sympathetic nervous system of the chick embryo.” Journal of Experimental Zoology. 116, no. 2 (1951): 321-61. Levi-Montalcini, R. “Effects of mouse tumor transplantation on the nervous system.” Annals of the New York Academy of Science. 55, no. 2 (1952): 330-44. Cohen, S., R. Levi-Montalcini, and V. Hamburger. “A Nerve Growth-Stimulating Factor Isolated from Sarcomas 37 and 180.” Proceedings of the National Academy of Sciences of the United States of America. 40, no. 10 (1954): 1014-8. Levi-Montalcini, R., H. Meyer, and V. Hamburger. “In vitro experiments on the effects of mouse sarcomas 180 and 37 on the spinal and sympathetic ganglia of the chick embryo.” Cancer Research. 14, no. 1 (1954): 49-57. Cohen, S. and R. Levi-Montalcini. “A Nerve Growth-Stimulating Factor Isolated from Snake Venom.” Proceedings of the National Academy of Sciences of the United States of America. 42, no. 9 (1956): 571-4. Levi-Montalcini, R. and S. Cohen. “In Vitro and In Vivo Effects of a Nerve Growth-Stimulating Agent Isolated from Snake Venom.” Proceedings of the National Academy of Sciences of the United States of America. 42, no. 9 (1956): 695-9. Levi-Montalcini, R. “Some trends in research on cellular differentiation and morphogenesis.” Journal of the National Cancer Institute. 19, no. 4 (1957): 609-25; discussion 626-41. Cohen, S. and R. Levi-Montalcini. “Purification and properties of a nerve growth-promoting factor isolated from mouse sarcoma 180.” Cancer Research. 17, no. 1 (1957): 15-20. Levi-Montalcini, R. and S. Cohen. “Effects of the extract of the mouse submaxillary salivary glands on the sympathetic system of mammals.” Annals of the New York Academy of Sciences. 85 (1960): 324-41. Levi-Montalcini, R. and B. Booker. “Destruction of the Sympathetic Ganglia in Mammals by an Antiserum to a Nerve-Growth Protein.” Proceedings of the National Academy of Sciences of the United States of America. 46, no. 3 (1960): 384-91. Levi-Montalcini, R. and B. Booker. “Excessive Growth of the Sympathetic Ganglia Evoked by a Protein Isolated from Mouse Salivary Glands.” Proceedings of the National Academy of Sciences of the United States of America. 46, no. 3 (1960): 373-84. Levi-Montalcini, R. and P.U. Angeletti. “Growth control of the sympathetic system by a specific protein factor.” Quarterly Review of Biology. 36 (1961): 99-108. Caramia, F., P.U. Angeletti, and R. Levi-Montalcini. “Experimental analysis of the mouse submaxillary salivary gland in relationship to its nerve-growth factor content.” Endocrinology. 70 (1962): 915-22. Levi-Montalcini, R. and P.U. Angeletti. “Growth and differentiation.” Annual Review of Physiology. 24 (1962): 11-56. Levi-Montalcini, R., P.U. Angeleti, and R.H. Lee. “Glycogen content in the heart of immunosympathectomized animals.” Archives Italiennes de Biologie. 100 (1962): 275-86. Levi-Montalcini, R. and P.U. Angeletti. “Essential role of the nerve growth factor in the survival and maintenance of dissociated sensory and sympathetic embryonic nerve cells in vitro.” Developmental Biology. 7 (1963): 653-9. Angeletti, P.U., A. Liuzzi, and R. Levi-Montalcini. “Stimulation of Lipid Biosynthesis in Sympathetic and Sensory Ganglia by a Specific Nerve Growth Factor.” Biochimica et Biophysica Acta. 84 (1964): 778-81. Levi-Montalcini, R. “The Nerve Growth Factor.” Annals of the New York Academy of Sciences. 118 (1964): 149-70. Angeletti, P.U., A. Liuzzi, R. Levi-Montalcini, and D. Gandiniattardi. “Effect of a Nerve Growth Factor on Glucose Metabolism by Sympathetic and Sensory Nerve Cells.” Biochimica et Biophysica Acta. 90 (1964): 445-50. Levi-Montalcini, R. “Growth Control of Nerve Cells by a Protein Factor and its Antiserum: Discovery of this Factor May Provide New Leads to Understanding of Some Neurogenetic Processes.” Science. 143 (1964): 105-10. Levi-Montalcini, R. and P.U. Angeletti. “Hormonal Control of the NGF Content in the Submaxillary Glands of Mice.” International Series of Monographs on Oral Biology. 3 (1964): 129-41. Levi-Montalcini, R. “Growth regulation of sympathetic nerve cells.” Archives Italiennes de Biologie. 103, no. 4 (1965): 832-46. Levi-Montalcini, R. “Morphological and metabolic effects of the nerve growth factor.” Archives de Biologie. 76, no. 2 (1965): 387-417. Liuzzi, A., P.U. Angeletti, and R. Levi-Montalcini. “Metabolic effects of a specific nerve growth factor (NGF) on sensory and sympathetic ganglia: Enhancement of lipid biosynthesis.” Journal of Neurochemistry. 12, no. 8 (1965): 705-8. Levi-Montalcini, R. “Ferdinando Morin (1912-1964).” Archives Italiennes de Biologie. 103 (1965): 335-7. Levi-Montalcini, R. “Tissue and Nerve Growth Promoting Factors. Biological Aspects of Specific Growth Promoting Factors.” Proceedings of the Royal Society of Medicine. 58 (1965): 357-60. Hamberger, B., R. Levi-Montalcini, K.A. Norberg, and F. Sjoeqvist. “Monoamines in Immunosympathectomized Rats.” International Journal of Neuropharmacology. 4 (1965): 91-5. Angeletti, P.U., D. Gandini-Attardi, G. Toschi, M.L. Salvi, and R. Levi-Montalcini. “Metabolic Aspects of the Effect of Nerve Growth Factor on Sympathetic and Sensory Ganglia: Protein and Ribonucleic Acid Synthesis.” Biochimica et Biophysica Acta. 95 (1965): 111-20. Sabatini, M.T., R. Levi-Montalcini, and P.U. Angeletti. “Early effects of anti-nerve growth factor serum on the nerve cell.” Annali dell’Istituto Superiore di Sanita. 2, no. 2 (1966): 349-55. Levi-Montalcini, R. “The nerve growth factor: Its mode of action on sensory and sympathetic nerve cells.” Harvey Lectures. 60 (1966): 217-59. Angeletti, P.U., A. Liuzzi, and R. Levi-Montalcini. “Effects of insulin on RNA and lipid synthesis in embryonal sensitive ganglia.” Annali dell’Istituto Superiore di Sanita. 2, no. 2 (1966): 420-2. Toschi, G., E. Dore, P.U. Angeletti, R. Levi-Montalcini, and C. de Haën. “Characteristics of labelled RNA from spinal ganglia of chick embryo and the action of a specific growth factor (NGF).” Journal of Neurochemistry. 13, no. 7 (1966): 539-44. Levi-Montalcini, R. and P.U. Angeletti. “Second symposium on catecholamines. Modification of sympathetic function. Immunosympathectomy.” Pharmacological Reviews. 18, no. 1 (1966): 619-28. Liuzzi, A., P.U. Angeletti, R. Levi-Montalcini, and G. Tacchini. “Glucose oxidation in the heart and diaphragm of immunosympathectomized animals.” Il Farmaco; Edizione Scientifica. 21, no. 3 (1966): 191-5. Angeletti, P., P. Calissano, J.S. Chen, and R. Levi-Montalcini. “Multiple molecular forms of the nerve growth factor.” Biochimica et Biophysica Acta. 147, no. 1 (1967): 180-2. Angeletti, P.U., R. Levi-Montalcini, and P. Calissano. “The nerve growth factor (NGF): Chemical properties and metabolic effects.” Advances in Enzymology and Related Areas of Molecular Biology. 31 (1968): 51-75. Zanini, A., P. Angeletti, and R. Levi-Montalcini. “Immunochemical properties of the nerve growth factor.” Proceedings of the National Academy of Sciences of the United States of America. 61, no. 3 (1968): 835-42. Levi-Montalcini, R. and P.U. Angeletti. “Nerve growth factor.” Physiological Reviews. 48, no. 3 (1968): 534-69. Levi-Montalcini, R., F. Caramia, S.A. Luse, and P.U. Angeletti. “In vitro effects of the nerve growth factor on the fine structure of the sensory nerve cells.” Brain Research. 8, no. 2 (1968): 347-62. Chen, J.S. and R. Levi-Montalcini. “Axonal outgrowth and cell migration in vitro from nervous system of cockroach embryos.” Science. 166, no. 905 (1969): 631-2. Levi-Montalcini, R., F. Caramia, and P.U. Angeletti. “Alterations in the fine structure of nucleoli in sympathetic neurons following NGF-antiserum treatment.” Brain Research. 12, no. 1 (1969): 54-73. Chen, J.S. and R. Levi-Montalcini. “Long term cultures of dissociated nerve cells from the embryonic nervous system of the cockroach Periplaneta americana.” Archives Italiennes de Biologie. 108, no. 4 (1970): 503-37. Angeletti, P.U. and R. Levi-Montalcini. “Cytolytic effect of 6-hydroxydopamine on neuroblastoma cells.” Cancer Research. 30, no. 12 (1970): 2863-9. Angeletti, P.U. and R. Levi-Montalcini. “Specific cytotoxic effect of 6-hydroxydopamine on sympathetic neuroblasts.” Archives Italiennes de Biologie. 108, no. 2 (1970): 213-21. Angeletti, P.U. and R. Levi-Montalcini. “Sympathetic nerve cell destruction in newborn mammals by 6-hydroxydopamine.” Proceedings of the National Academy of Sciences of the United States of America. 65, no. 1 (1970): 114-21. Chen, J.S. and R. Levi-Montalcini. “Axonal Growth from Insect Neurons in Glia-Free Cultures.” Proceedings of the National Academy of Sciences of the United States of America. 66, no. 1 (1970): 32-39. Levi-Montalcini, R. and P.U. Angeletti. “Two control mechanisms of growth and differentiation of the sympathetic nervous system.” UCLA Forum in Medical Sciences. 14 (1971): 253-68. Levi-Montalcini, R. and J.S. Chen. “Selective outgrowth of nerve fibers in vitro from embryonic ganglia of Periplaneta americana.” Archives Italiennes de Biologie. 109, no. 4 (1971): 307-37. Angeletti, P.U. and R. Levi-Montalcini. “Growth regulation of the sympathetic nervous system: Immunosympathectomy and chemical sympathectomy.” Revue Europeenne d’etudes cliniques et biologiques. European Journal of Clinical and Biological Research. 16, no. 9 (1971): 866-74. Thoenen, H, P.U. Angeletti, R. Levi-Montalcini, and R. Kettler. “Selective Induction by Nerve Growth Factor of Tyrosine Hydroxylase and Dopamine-β-Hydroxylase in the Rat Superior Cervical Ganglia.” Proceedings of the National Academy of Sciences of the United States of America. 68, no. 7 (1971): 1598-602. Angeletti, P.U., R. Levi-Montalcini, and F. Caramia. “Ultrastructural changes in sympathetic neurons of newborn and adult mice treated with nerve growth factor.” Journal of Ultrastructure Research. 36, no. 1 (1971): 24-36. Seshan, K.R. and R. Levi-Montalcini. “In vitro analysis of corpora cardiaca and corpora allata from nymphal and adult specimens of Periplaneta americana.” Archives Italiennes de Biologie. 109, no. 2 (1971): 81-109. Angeletti, P.U., R. Levi-Montalcini, and F. Caramia. “Analysis of the effects of the antiserum to the nerve growth factor in adult mice.” Brain Research. 27, no. 2 (1971): 343-55. Angeletti, R.H., P.U. Angeletti, and R. Levi-Montalcini. “Selective accumulation of (125 I) labelled nerve growth factor in sympathetic ganglia.” Brain Research. 46 (1972): 421-5. Levi-Montalcini, R. and L. Aloe. “Neuronal nets and nerve cell interactions in vitro in insect systems.” In Vitro. 8, no. 3 (1972): 178-93. Aloe, L. and R. Levi-Montalcini. “In vitro analysis of the frontal and ingluvial ganglia from nymphal specimens of the cockroach Periplaneta americana.” Brain Research. 44, no. 1 (1972): 147-63. Angeletti, P.U., R. Levi-Montalcini, R. Kettler, and H. Thoenen. “Comparative studies on the effect of the nerve growth factor on sympathetic ganglia and adrenal medulla in newborn rats.” Brain Research. 44, no. 1 (1972): 197-206. Angeletti, P.U., R. Levi-Montalcini, and F. Caramia. “Structural and ultrastructural changes in developing sympathetic ganglia induced by guanethidine.” Brain Research. 43, no. 2 (1972): 515-25. Aloe, L. and R. Levi-Montalcini. “Interrelation and dynamic activity of visceral muscle and nerve cells from insect embryos in long-term cultures.” Journal of Neurobiology. 3, no. 1 (1972): 3-23. Caramia, F., P.U. Angeletti, R. Levi-Montalcini, and L. Carratelli. “Mitochondrial lesions of developing sympathetic neurons induced by bretylium tosylate.” Brain Research. 40, no. 2 (1972): 237-46. Thoenen, H., A. Saner, P.U. Angeletti, and R. Levi-Montalcini. “Increased activity of choline acetyltransferase in sympathetic ganglia after prolonged administration of nerve growth factor.” Nature: New Biology. 236, no. 62 (1972): 26-8. Angeletti, P.U. and R. Levi-Montalcini. “Growth inhibition of sympathetic cells by some adrenergic blocking agents (6-hydroxydopamine-mice and rats-immunosympathectomy-chemical sympathectomy-superior cervical ganglion).” Proceedings of the National Academy of Sciences of the United States of America. 69, no. 1 (1972): 86-8. Seshan, K.R. and R. Levi-Montalcini. “Neuronal properties of nymphal and adult insect neurosecretory cells in vitro.” Science. 182, no. 4109 (1973): 291-3. Levi-Montalcini, R., L. Aloe, and E.M. Johnson, Jr. “Interaction between nerve growth factor (NGF) and adrenergic blocking agents in sympathetic neurons.” Life Sciences. 13, no. 6 (1973): cii-ciii. Levi-Montalcini, R., L. Aloe, and E.M. Johnson, Jr. “Interaction between the nerve growth factor (NGF) and adrenergic blocking agents in sympathetic neurons.” Biochemical Pharmacology. 23, Suppl. 1 (1974): 199-208. Levi-Montalcini, R., R. Revoltella, and P. Calissano. “Microtubule proteins in the nerve growth factor mediated response. Interaction between the nerve growth factor and its target cells.” Recent Progress in Hormone Research. 30 (1974): 635-69. Seshan, K.R., R.R. Provine, and R. Levi-Montalcini. “Structural and electrophysiological properties of nymphal and adult insect medial neurosecretory cells: An in vitro analysis.” Brain Research. 78, no. 3 (1974): 359-76. Aloe, L., E. Mugnaini, and R. Levi-Montalcini. “Light and electron microscopic studies on the excessive growth of sympathetic ganglia in rats injected daily from birth with 6 OHDA and NGF.” Archives Italiennes de Biologie. 113, no. 4 (1975): 326-53. Levi-Montalcini, R., L. Aloe, and E. Mugnaini. “Nerve growth factor induces volume increase and enhances tyrosine hydroxylase synthesis in chemically axotomized sympathetic ganglia of newborn rats.” Proceedings of the National Academy of Sciences of the United States of America. 72, no. 2 (1975): 595-9. Calissano, P., A. Levi, S. Alemà, J. Chen, and R. Levi-Montalcini. “Proceedings: Studies on the interaction of nerve growth factor with tubulin and actin.” Hoppe-Seyler’s Zeitschrift fur Physiologische Chemie. 356, no. 4 (1975): 382-3. Levi-Montalcini, R. “Nerve growth factor.” Science. 187, no. 4172 (1975): 113. Levi-Montalcini, R. “The nerve growth factor: Its widening role and place in neurobiology.” Advances in Biochemical Psychopharmacology. 15 (1976): 237-50. Levi-Montalcini, R. “Nerve growth factor in familial dysautonomia.” New England Journal of Medicine. 295, no. 12 (1976): 671-3. Levi-Montalcini, R. “The nerve growth factor: Its role in growth, differentiation and function of the sympathetic adrenergic neuron.” Progress in Brain Research. 45 (1976): 235-58. Levi-Montalcini, R. “Toxicity of psychotropic drugs on aminergic neurons.” Psychopharmacology Bulletin. 12, no. 2 (1976): 57-8. Chen, M.G., J.S. Chen, P. Calissano, and R. Levi-Montalcini. “Nerve growth factor prevents vinblastine destructive effects on sympathetic ganglia in newborn mice.” Proceedings of the National Academy of Sciences of the United States of America. 74, no. 12 (1977): 5559-63. Aloe, L. and R. Levi-Montalcini. “Mast cells increase in tissues of neonatal rats injected with the nerve growth factor”. Brain Research. 133, no. 2 (1977): 358-66. Liuzzi, A., F.H. Foppen, J.M. Saavedra, R. Levi-Montalcini, and I.J. Kopin. “Gas chromatographic-mass spectrometric assay of serotonin in rat superior cervical ganglia. Effects of nerve growth factor and 6-hydroxydopamine.” Brain Research. 133, no. 2 (1977): 354-7. Menesini, Chen M.G., J.S. Chen, and R. Levi-Montalcini. “Sympathetic nerve fibers ingrowth in the central nervous system of neonatal rodent upon intracerebral NGF injections.” Archives Italiennes de Biologie. 116, no. 1 (1978): 53-84. Levi-Montalcini, R. “The sympathetic nerve cell as a model system of nerve cell growth and differentiation.” Gaslini. 11, no. 2 (1979): 109-22. Aloe, L. and R. Levi-Montalcini. “Nerve growth factor induced overgrowth of axotomized superior cervical ganglia in neonatal rats. Similarities and differences with NGF effects in chemically axotomized sympathetic ganglia.” Archives Italiennes de Biologie. 117, no. 4 (1979): 287-307. Levi-Montalcini, R. “Trophic, tropic and transforming effects of the nerve growth factor on its target cells.” Bulletin et Memoires de l’Academie Royale de Medecine de Belgique. 134, no. 4 (1979): 217-28. Calissano, P. and R. Levi-Montalcini. “Is NGF an enzyme?” Nature. 280, no. 5721 (1979): 359. Levi-Montalcini, R. and P. Calissano. “The nerve-growth factor.” Scientific American. 240, no. 6 (1979): 68-77. Levi-Montalcini, R. “Recent studies on the NGF-target cells interaction.” Differentiation. 13, no. 1 (1979): 51-3. Aloe, L. and R. Levi-Montalcini. “Nerve growth factor-induced transformation of immature chromaffin cells in vivo into sympathetic neurons: Effect of antiserum to nerve growth factor.” Proceedings of the National Academy of Sciences of the United States of America. 76, no. 3 (1979): 1246-50. Levi-Montalcini, R. and L. Aloe. “Tropic, trophic, and transforming effects of nerve growth factor.” Advances in Biochemical Psychopharmacology. 25 (1980): 3-15. Aloe, L. and R. Levi-Montalcini. “Comparative studies on the effects elicited by pre- and postnatal injections of anti-NGF, guanethidine, and 6-hydroxydopamine in chromaffin and ganglion cells of the adrenal medulla and carotid body in infant rats.” Advances in Biochemical Psychopharmacology. 25 (1980): 221-6. Levi-Montalcini, R. “Polydipsia after intracranial injections – a property of NGF or a contaminant?” Nature. 284, no. 5756 (1980): 577. Aloe, L. and R. Levi-Montalcini. “Enhanced differentiation of sexually dimorphic organs in L-thyroxine treated Tfm mice.” Cell and Tissue Research. 205, no. 1 (1980): 19-29. Aloe, L. and R. Levi-Montalcini. “Comparative studies on testosterone and L-thyroxine effects on the synthesis of nerve growth factor in mouse submaxillary salivary glands.” Experimental Cell Research. 125, no. 1 (1980): 15-22. Aloe, L., C. Cozzari, P. Calissano, and R. Levi-Montalcini. “Somatic and behavioural postnatal effects of fetal injections of nerve growth factor antibodies in the rat.” Nature. 291, no. 5814 (1981): 413-5. Aloe, L., C. Cozzari, and R. Levi-Montalcini. “The submaxillary salivary glands of the African rodent Praomys (mastomys) natalensis as the richest available source of the growth factor.” Experimental Cell Research. 133, no. 2 (1981): 475-80. Levi-Montalcini, R. “Nerve growth factor – target cells. A model of choice in the study of neuron differentiation.” Bollettino dell’Istituto Sieroterapico Milanese. 61, no. 2 (1982): 164-9. Aloe, L., P. Calissano, and R. Levi-Montalcini. “Effects of oral administration of nerve growth factor and of its antiserum on sympathetic ganglia of neonatal mice.” Brain Research. 256, no. 1 (1982): 31-4. Levi-Montalcini, R. “Developmental neurobiology and the natural history of nerve growth factor.” Annual Review of Neuroscience. 5 (1982): 341-62. Aloe, L., P. Calissano, and R. Levi-Montalcini. “Effects of oral administration of nerve growth factor and of its antiserum on sympathetic ganglia of neonatal mice.” Developmental Brain Research. 4, no. 1 (1982): 31-4. Levi-Montalcini, R. “The nerve growth factor-target cells interaction: A model system for the study of directed axonal growth and regeneration.” Birth Defects: Original Article Series. 19, no. 4 (1983): 3-22. Calissano, P., A. Cattaneo, S. Biocca, L. Aloe, D. Mercanti, and R. Levi-Montalcini. “The nerve growth factor. Established findings and controversial aspects.” Experimental Cell Research. 154, no. 1 (1984): 1-9. Levi-Montalcini, R. and L. Aloe. “Differentiating effects of murine nerve growth factor in the peripheral and central nervous systems of Xenopus laevis tadpoles.” Proceedings of the National Academy of Sciences of the United States of America. 82, no. 20 (1985): 7111-5. Aloe, L., C. Cozzari, and R. Levi-Montalcini. “Cyclocytidine-induced release of nerve growth factor from mouse submandibular glands enhances regeneration of sympathetic fibers in adults mice.” Brain Research. 332, no. 2 (1985): 259-65. Levi-Montalcini, R. and P. Calissano. “Nerve growth factor as a paradigm for other polypeptide growth factors.” Trends in Neurosciences. 9, no. 10 (1986): 473-7. Aloe, L., E. Alleva, A. Bohm, and R. Levi-Montalcini. “Aggressive behavior induces release of nerve growth factor from mouse salivary gland into the bloodstream.” Proceedings of the National Academy of Sciences of the United States of America. 83, no. 16 (1986): 6184-7. Levi-Montalcini, R. “The nerve growth factor: Thirty-five years later.” Bioscience Reports. 7, no. 9 (1987): 681-99. Levi-Montalcini, R. “The nerve growth factor: Thirty-five years later.” EMBO Journal. 6, no. 5 (1987): 1145-54. Levi-Montalcini, R. “The nerve growth factor thirty-five years later.” In Vitro Cellular & Developmental Biology: Journal of the Tissue Culture Association. 23, no. 4 (1987): 227-38. Levi-Montalcini, R. “The nerve growth factor 35 years later.” Science. 237, no. 4819 (1987): 1154-62. Levi-Montalcini, R. “The nerve growth factor: 35 years later (Nobel lecture).” Angewandte Chemie – International Edition in English. 26, no 8 (1987): 707-16. Spillantini, M.G., L. Aloe, E. Alleva, R. De Simone, M. Goedert, and R. Levi-Montalcini. “Nerve growth factor mRNA and protein increase in hypothalamus in a mouse model of aggression.” Proceedings of the National Academy of Sciences of the United States of America. 86, no. 21 (1989): 8555-9. Aloe, L., M.A. Tuveri, and R. Levi-Montalcini. “Nerve growth factor and distribution of mast cells in the synovium of adult rats.” Clinical and Experimental Rheumatology. 10, no. 2 (1992): 203-4. Aloe, L., M.A. Tuveri, U. Carcassi, and R. Levi-Montalcini. “Nerve growth factor in the synovial fluid of patients with chronic arthritis.” Arthritis and Rheumatism. 35, no. 3 (1992): 351-5. Aloe, L., M.A. Tuveri, and R. Levi-Montalcini. “Studies on carrageenan-induced arthritis in adult rats: Presence of nerve growth factor and role of sympathetic innervation.” Rheumatology International. 12, no. 5 (1992): 213-6. Laudiero, L.B., L. Aloe, R. Levi-Montalcini, C. Buttinelli, D. Schilter, S. Gillessen, and U. Otten. “Multiple sclerosis patients express increased levels of β-nerve growth factor in cerebrospinal fluid.” Neuroscience Letters. 147, no. 1 (1992): 9-12. Aloe, L., E. Vigneti, R. Cavalieri, B. Didona, L. Bracci-Laudiero, C. Mazzanti, G. Papa, R. Stasi, and R. Levi-Montalcini. “Presence of nerve growth factor and NGF-receptors in human schwannoma cells.” Clinical Chemistry and Enzymology Communications. 5, no. 4-6 (1993): 309-13. Aloe, L., L. Probert, G. Kollias, L. Bracci-Laudiero, A. Micera, C. Mollinari, and R. Levi-Montalcini. “Level of nerve growth factor and distribution of mast cells in the synovium of tumour necrosis factor transgenic arthritic mice.” International Journal of Tissue Reactions. 15, no. 4 (1993): 139-43. Aloe, L., A. Leon, and R. Levi-Montalcini. “A proposed autacoid mechanism controlling mastocyte behaviour.” Agents and Actions. 39, Special Issue (1993): C145-7. Luppi, P., R. Levi-Montalcini, L. Bracci-Laudiero, A. Bertolini, R. Arletti, D. Tavernari, E. Vigneti, and L. Aloe. “NGF is released into plasma during human pregnancy: An oxytocin-mediated response?” NeuroReport. 4, no. 8 (1993): 1063-5. Aloe, L., L. Probert, G. Kollias, L. Bracci-Laudiero, M.G. Spillantini, and R. Levi-Montalcini. “The synovium of transgenic arthritic mice expressing human tumor necrosis factor contains a high level of nerve growth factor.” Growth Factors. 9, no. 2 (1993): 149-55. Bracci-Laudiero, L., L. Aloe, R. Levi-Montalcini, M. Galeazzi, D. Schilter, J.L. Scully, and U. Otten. “Increased levels of NGF in sera of systemic lupus erythematosus patients.” NeuroReport. 4, no. 5 (1993): 563-5. Aloe, L., S.D. Skaper, A. Leon, and R. Levi-Montalcini. “Nerve growth factor and autoimmune diseases.” Autoimmunity. 19, no. 2 (1994): 141-50. Leon, A., A. Buriani, R. Dal Toso, M. Fabris, S. Romanello, L. Aloe, and R. Levi-Montalcini. “Mast cells synthesize, store, and release nerve growth factor.” Proceedings of the National Academy of Sciences of the United States of America. 91, no. 9 (1994): 3739-43. Changeux, J.P., P. Andersen, M. J. Berridge, C. Blakemore, T. Bliss, Alberto Ferrus Gamero, T. Freund, R. Grantyn, S. Grillner, K. Hepp, T. Hökfelt, J. Hounsgaard, H. Korn, R. Levi-Montalcini, R. Miles, J.-C. Schwartz, W. Singer, P. Strata, E. S. Vizi, W. Wadman and S. Zeki. “European brain research [1].” Nature. 369, no. 6482 (1994): 601. Levi-Montalcini, R. “‘Polypeptide growth factors’ with special emphasis on wound healing. introduction.” Cell Biology International. 19, no. 5 (1995): 355. Levi-Montalcini, R., R. Dal Toso, F. della Valle, S.D. Skaper, and A. Leon. “Update of the NGF saga.” Journal of the Neurological Sciences. 130, no. 2 (1995): 119-27. Levi-Montalcini, R., S.D. Skaper, R. Dal Toso, L. Petrelli, and A. Leon. “Nerve growth factor: From neurotrophin to neurokine.” Trends in Neurosciences. 19, no. 11 (1996): 514-20. Levi-Montalcini, R. “The saga of the nerve growth factor.” NeuroReport. 9, no. 16 (1998): R71-83. Garaci, E., M.C. Caroleo, L. Aloe, S. Aquaro, M. Piacentini, N. Costa, A. Amendola, A. Micera, R. Caliò, C.-F. Perno, and R. Levi-Montalcini. “Nerve growth factor is an autocrine factor essential for the survival of macrophages infected with HIV.” Proceedings of the National Academy of Sciences of the United States of America. 96, no. 24 (1999): 14013-8. Levi-Montalcini, R. “Preface to Structural and Functional Studies on Nerve Growth Factor.” Microscopy Research and Technique. 45, no. 4-5 (1999): 205. Levi-Montalcini, R. “From Turin to Stockholm via St. Louis and Rio de Janeiro.” Science. 287, no. 5454 (2000): 809. Levi-Montalcini, R. “From a home-made laboratory to the Nobel Prize: an interview with Rita Levi-Montalcini.” International Journal of Developmental Biology. 44, no. 6 (2000): 563-6. Calzà, L., L. Giardino, A. Giuliani, L. Aloe, and R. Levi-Montalcini. “Nerve growth factor control of neuronal expression of angiogenetic and vasoactive factors.” Proceedings of the National Academy of Sciences of the United States of America. 98, no. 7 (2001): 4160-5. Levi-Montalcini, R. “The nerve growth factor and the neuroscience chess board.” Archives Italiennes de Biologie. 141, no. 2-3 (2003): 85-8. Fernandez, M., A. Giuliani, S. Pirondi, G. D’Intino, L. Giardino, L. Aloe, R. Levi-Montalcini, and L. Calzà. “Thyroid hormone administration enhances remyelination in chronic demyelinating inflammatory disease.” Proceedings of the National Academy of Sciences of the United States of America. 101, no. 46 (2004): 16363-8. Levi-Montalcini, R. “The nerve growth factor and the neuroscience chess board.” Progress in Brain Research. 146 (2004): 525-7. Levi-Montalcini, R. “Ten years in cell death: A double celebration.” Cell Death and Differentiation. 11, no. 1 (2004): 1. Colangelo, A.M., N. Finotti, M. Ceriani, L. Alberghina, E. Martegani, L. Aloe, L. Lenzi, and R. Levi-Montalcini. “Recombinant human nerve growth factor with a marked activity in vitro and in vivo.” Proceedings of the National Academy of Sciences of the United States of America. 102, no. 51 (2005): 18658-63. Levi-Montalcini, R. and P. Calissano. “The scientific challenge of the 21st century: from a reductionist to a holistic approach via systems biology.” BMC Neuroscience. 7, Suppl. 1 (2006): S1.

Referenties

[1]: Manca A, Capsoni S, Di Luzio A, Vignone D, Malerba F, Paoletti F, Brandi R, Arisi I, Cattaneo A, Levi-Montalcini R. | Nerve growth factor regulates axial rotation during early stages of chick embryo development. | Proc Natl Acad Sci U S A. | 2012 Feb 7;109(6):2009-14. doi: 10.1073/pnas.1121138109. Epub 2012 Jan 25.
[2]: Hack A, Selenka F. | Mobilization of PAH and PCB from contaminated soil using a digestive tract model. | Toxicol Lett. | 1996 Nov;88(1-3):199-210.
[3]: Aloe L, Leon A, Levi-Montalcini R. | A proposed autacoid mechanism controlling mastocyte behaviour. | Agents Actions. | 1993;39 Spec No:C145-7.
[4]: Leon A, Buriani A, Dal Toso R, Fabris M, Romanello S, Aloe L, Levi-Montalcini R. | Mast cells synthesize, store, and release nerve growth factor. | Proc Natl Acad Sci U S A. | 1994 Apr 26;91(9):3739-43.
[5]: Aloe L, Probert L, Kollias G, Bracci-Laudiero L, Micera A, Mollinari C, Levi-Montalcini R. | Level of nerve growth factor and distribution of mast cells in the synovium of tumour necrosis factor transgenic arthritic mice. | Int J Tissue React. | 1993;15(4):139-43.
[6]: Levi-Montalcini R, Skaper SD, Dal Toso R, Petrelli L, Leon A. | Nerve growth factor: from neurotrophin to neurokine. | Trends Neurosci. | 1996 Nov;19(11):514-20.
[7]: Skaper SD, Facci L. | Mast cell-glia axis in neuroinflammation and therapeutic potential of the anandamide congener palmitoylethanolamide. | Philos Trans R Soc Lond B Biol Sci. | 2012 Dec 5;367(1607):3312-25. doi: 10.1098/rstb.2011.0391.
[8]: Truini A, Biasiotta A, Di Stefano G, La Cesa S, Leone C, Cartoni C, Federico V, Petrucci MT, Cruccu G. | Palmitoylethanolamide restores myelinated-fibre function in patients with chemotherapy-induced painful neuropathy. | CNS Neurol Disord Drug Targets. | 2011 Dec;10(8):916-20.
[9]: Hesselink JM, Hekker TA. | Therapeutic utility of palmitoylethanolamide in the treatment of neuropathic pain associated with various pathological conditions: a case series. | J Pain Res. | 2012;5:437-42. doi: 10.2147/JPR.S32143. Epub 2012 Oct 26.
[10]: Kalra S, Baruah MP, Unnikrishnan AG. | Celebrating life with Rita Levi-Montalcini: A hundred years and more. | Indian J Endocrinol Metab. | 2012 May;16(3):327-8. doi: 10.4103/2230-8210.95657.
[11]: [No authors listed] | Festschrift in celebration of Rita Levi-Montalcini’s 102nd birthday. | Mol Neurobiol. | 2011 Apr;43(2):77-146.

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