Laboratory of Neuroendocrinology
The main goal of our research group is the study of neuroactive steroids in the central and peripheral nervous system, characterizing the molecular mechanisms of their effects in physiological experimental models as well as in those of neurodegenerative (i.e. multiple sclerosis, Parkinson's, Alzheimer's, neurodevelopmental diseases, etc.) and in psychiatric (i.e. depression and anxiety) disorders. A particular attention is given to sexual differences.
The specific objectives are:
Characterization of the persistent side-effects of finasteride (an inhibitor of the enzyme 5alpha-reductase) in the male rat and in patients (post-finasteride syndrome), with particular relevance to sexual dysfunction and its neuroendocrine control, mood disorder and gut-microbiota-brain axis.
Evaluation of persistent side-effects of antidepressant drugs (SSRIs) in the male rat, with particular relevance to sexual dysfunction and its neuroendocrine control and to neurosteroidogenesis.
Identification of the epigenetic mechanisms linked to the long-term alterations associated with finasteride treatment.
Characterization of neuroprotective effects of neuroactive steroids in diabetes mellitus (i.e. encephalopathy and peripheral neuropathy).
Evaluation of neurosteroidogenesis and neuroactive steroid levels in male and in female experimental models, with particular relevance to their pathophysiological role.
The research activity is performed analyzing by in vivoandin vitroexperimental models, the molecular markers involved in the etiology of the pathologies as well as in the action of the drugs considered.
In this regard, the experimental techniques used are:
- extraction of nucleic acids and proteins from tissue and/or cells
- analysis of gene expression by Real-Time PCR
- analysis of protein expression by Western Blotting
- Bisulfite Conversion of DNA or Methylation-sensitive restriction enzymes (MSREs) for site-specific methylation analysis
- Determination of enzymatic activity by spectrophotometric techniques
- The enzyme-linked immunosorbent assay (ELISA)
- Immunohistochemistry (IHC) - confocal microscopy
- Morphological analysis of nervous cells
- Behavioral tests in experimental models
- Assessment by Liquid chromatography–mass spectrometry (LC-MS) (collaboration with Prof. D. Caruso)
- Luis Miguel Garcia-Segura, Instituto Cajal - Madrid (Spain)
- Donatella Caruso, Università degli Studi di Milano – Milan (Italy)
- Charlotte Kilstrup-Nielsen, Università Insubria, Busto Arsizio (Italy)
- Roberto Frau, Università degli Studi di Cagliari – Cagliari (Italy)
- Guido Cavaletti, Università degli Studi Milano-Bicocca – Monza (Italy)
- Giancarlo Panzica, Università degli Studi di Torino – Turin (Italy)
- Siobhain O’Mahony, University College Cork – (Ireland)
Giatti S., Garcia-Segura L.M., Barreto G.E., Melcangi R.C. Neuroactive steroids, neurosteroidogenesis and sex. Prog Neurobiol 2018, PubMedPMID: 29981391.
Tetel M.J., de Vries G.J., Melcangi R.C., Panzica G., O'Mahony S.M. Steroids, stress and the gut microbiome-brain axis. J Neuroendocrinol 2018, PubMed PMID: 29024170.
Giatti S., Mastrangelo R., D'Antonio M., Pesaresi M., Romano S., Diviccaro S., Caruso D., Mitro N., Melcangi R.C. Neuroactive steroids and diabetic complications in the nervous system. Front Neuroendocrinol 48:58-69, 2018.
Melcangi R.C., Giatti S., Garcia-Segura L.M. Levels and actions of neuroactive steroids in the nervous system under physiological and pathological conditions: sex-specific features. Neurosci Biobehav Rev 67:25-40, 2016.