Lab-Neuroendocrinology

Research activity
Our major fields of interest are focused on the effects of neuroactive steroids, like for instance progesterone (P), testosterone (T) and its derivatives, at the level of nervous system in order to understand whether these molecules may be effective as new therapeutic approaches to counteract neurodegeneration. In particular, during the last few years, we have concentrated our efforts on assessing the possible effects of neuroactive steroids on myelin and axonal compartment of peripheral nerves. We have demonstrated that neuroactive steroids are able to influence the expression of glycoprotein P0 and peripheral myelin protein 22, both in vitro (e.g., utilizing cultures of rat Schwann cells) and in vivo (sciatic nerve of adult and aged rats). Moreover, we have also demonstrated that P and its derivatives (i.e., dihydroprogesterone, DHP and tetrahydroprogesterone, THP) are able to positively affect the morphology of sciatic nerve of aged male rats. Indeed, treatment with these neuroactive steroids, counteract aging-associated morphological alterations of peripheral nerves.

Laboratory of Neuroendocrinology Supervisor Prof. Roberto Cosimo Melcangi, PhD Associate Professor Tel. +39-02-50318238 Fax: +39-02-50318204 Email: roberto.melcangi@unimi.it
	Staff Valerio Magnaghi - Assistant Professor, PhD Marinella Ballabio -Technician Emanuela Leonelli -PostDoc Antonio Consoli -Student Ilaria Roglio -Student Elena Crespi -Student Raffaella Busnelli -Student

Research activity Our major fields of interest are focused on the effects of neuroactive steroids, like for instance progesterone (P), testosterone (T) and its derivatives, at the level of nervous system in order to understand whether these molecules may be effective as new therapeutic approaches to counteract neurodegeneration. In particular, during the last few years, we have concentrated our efforts on assessing the possible effects of neuroactive steroids on myelin and axonal compartment of peripheral nerves. We have demonstrated that neuroactive steroids are able to influence the expression of glycoprotein P0 and peripheral myelin protein 22, both in vitro (e.g., utilizing cultures of rat Schwann cells) and in vivo (sciatic nerve of adult and aged rats). Moreover, we have also demonstrated that P and its derivatives (i.e., dihydroprogesterone, DHP and tetrahydroprogesterone, THP) are able to positively affect the morphology of sciatic nerve of aged male rats. Indeed, treatment with these neuroactive steroids, counteract aging-associated morphological alterations of peripheral nerves.
Selected publications (2001-2004) - Cavarretta I.T.R., Martini L., Motta M., Smith C.L., Melcangi R.C. SRC-1 is involved in the control of the gene expression of myelin protein Po. J. Mol. Neurosci. 24:217-226, 2004. - Magnaghi V., Ballabio M., Cavarretta I.T.R., Froestl W., Lambert J.J., Zucchi I., Melcangi R.C. GABA-B receptors in Schwann cells influence proliferation and myelin protein expression. European J. Neurosci. 19:2641-2649, 2004. - Magnaghi V., Ballabio M., Gonzalez L.C., Leonelli E., Motta M., Melcangi R.C. The synthesis of glycoprotein Po and peripheral myelin protein 22 in sciatic nerve of male rats is modulated by testosterone metabolites. Mol. Brain Res. 126:67-73, 2004. - Melcangi R.C., Azcoitia I., Ballabio M., Cavarretta I., Gonzalez L.C., Leonelli E., Magnaghi V., Veiga S., Garcia-Segura L.M. Neuroactive steroids influence peripheral myelination: a promising opportunity for preventing or treating age-dependent dysfunctions of peripheral nerves. Prog. Neurobiol. 71:57-66,2003. - Melcangi R.C., Leonelli E., Magnaghi V., Gherardi G., Nobbio L., Schenone A. Mifepristone (RU 38486) influences expression of glycoprotein Po and morphological parameters at the level of rat sciatic nerve: in vivo observations. Exp. Neurol. 184: 930-938, 2003. - Azcoitia I., Leonelli E., Magnaghi V., Veiga S., Garcia-Segura L.M., Melcangi R.C. Progesterone and its derivatives dihydroprogesterone and tetrahydroprogesterone reduce myelin fiber morphological abnormalities and myelin fiber loss in the sciatic nerve of aged rats. Neurobiol Aging 24:853-860, 2003. - Garcia-Segura L.M., Veiga S., Sierra A., Melcangi R.C., Azcoitia I. Aromatase: a neuroprotective enzyme. Prog. Neurobiol. 71:31-41, 2003. - Giachino C., Galbiati M., Fasolo A., Peretto P., Melcangi R.C. Effects of progesterone derivatives, dihydroprogesterone and tetrahydroprogesterone, on the subependymal layer of the adult rat. J. Neurobiol. 58:493-502, 2004. - Schumacher M., Weill-Engerer S., Liere P., Robert F., Franklin R.J., Garcia-Segura L.M., Lambert J.J., Mayo W., Melcangi R.C., Parducz A., Suter U., Carelli C., Baulieu E.E., Akwa Y. Steroid hormones and neurosteroids in normal and pathological aging of the nervous system. Prog. Neurobiol. 71:3-29, 2003. - Ibanez C., Shields S.A., El-Etr M., Leonelli E., Magnaghi V., Li W.W., Sim F.J., Baulieu E.E., Melcangi R.C., Schumacher M., Franklin R.J. Steroids and the reversal of age-associated changes in myelination and remyelination. Prog. Neurobiol. 71:49-56, 2003. - Magnaghi V., Cavarretta I., Galbiati M., Martini L., Melcangi R.C. Neuroactive steroids and peripheral myelin proteins. Brain Res. Rev. 37:360-371, 2001.
Links and additional informations INTERNATIONAL MEETING: STEROIDS AND NERVOUS SYSTEM http://www.dafml.unito.it/anatomy/panzica/neurosteroids/index.html