Laboratory of di Psycopharmacology and Molecular Psychiatry
Head Prof. Marco Andrea RIVA M.Riva@unimi.it
Fabio Fumagalli Associate Professor Fabio.Fumagalli@unimi.it
Raffaella Molteni Assistant Professor Raffaella.Molteni@unimi.it
Francesca Calabrese Research Assistant Francesca.Calabrese@unimi.it
Lucia Caffino Research Assistant Lucia.Caffino@unimi.it
Annamaria Cattaneo Visiting Scientist firstname.lastname@example.org
Alessia Luoni Ph.D. Student Alessia.Luoni@unimi.it
Flavia Macchi Ph.D. Student Flavia.Macchi@unimi.it
Juliet Richetto Ph.D. Student Juliet.Richetto@unimi.it
Giuseppe Giannotti Ph.D. Student Giuseppe.Giannotti@unimi.it
The primary research goal of the laboratory is the investigation of the molecular mechanisms that might be disrupted in psychiatric illnesses, including depression, schizophrenia and substance abuse, to establish how pharmacological treatments can restore normal brain function as well as to identify targets for the development of novel therapeutic intervention. Within this context, major goal of our studies are:
- Understand how genes and adverse early life experiences may enhance the vulnerability to psychiatric disorders, such as depression, schizophrenia and autism.
- Investigate and characterize the molecular effects of stress and its impact on psychopathology.
- Characterize the contribution of epigenetic mechanisms for long-term dysfunction in psychiatric disorders.
- Investigate the role for neurotrophic mechanisms in long-term brain dysfunction and characterize the regulatory mechanisms for their production and function within the central nervous system.
- Analyze the molecular mechanisms underlying the action of psychotropic drugs.
- Investigate the role of glutamate in schizophrenia-related symptomatology and the therapeutic impact of its pharmacological modulation.
- Understand the role of inflammation in the etiology of psychiatric disorders and in the mechanism of action of psychotropic drugs (coordinated by Dr. R. Molteni).
- Analyze the molecular substrates for the action of drugs of abuse: evidence from adolescent and adult animal models (coordinated by Prof. F. Fumagalli).
The experimental activity is conducted through preclinical studies providing a detailed quantitative analyses at cerebral level of molecular systems altered and/or involved in the etiology of psychiatric disorders and in the action of psychotropic drugs. To this end, several biochemical and cell/molecular biological techniques are employed to analyze DNA, mRNA and protein. Epigenetic studies are carried out on DNA through chromatin immunoprecipitation for histone changes as well as methylation changes on target genes as well as on whole genome (methylome studies). Real time PCR and microarray are used for the gene expression analyses, while ELISA and western blotting are used to investigate changes at protein levels. In addition, in vivo behavioral tests are also performed to assess the development of pathological phenotypes.
- Roceri M., Cirulli F., Pessina C., Peretto P., Racagni G. and Riva M.A. Postnatal repeated maternal deprivation produces age dependent changes of BDNF expression in selected rat brain regions. Biological Psychiatry 55:708-14, 2004
- Fumagalli F., Frasca A., Racagni G. and Riva M.A. Dynamic regulation of glutamatergic post-synaptic activity in rat prefrontal cortex by repeated administration of antipsychotic drugs Molecular Pharmacology, 73:1484-1490, 2008.
- Molteni R., Calabrese F., Cattaneo A., Mancini M., Gennarelli M., RacagniG.and Riva M.A. Acute stress responsiveness of the neurotrophin BDNF in the rat hippocampus is modulated by chronic antidepressant treatment. Neuropsychopharmacology. 34:1523-32, 2009
- Calabrese F., Molteni R. and Riva M.A. Anti-stress properties of antidepressant drugs and their clinical implications. Pharmacology and Therapeutics, 132:39-56, 2011.
- Fumagalli F., Moro F., Caffino L., Orrù A., Cassina C., Giannotti G., Di Clemente A., Racagni G., Riva M.A., Cervo L. Region-specific effects on BDNF expression after contingent or non-contingent cocaine intravenous self-administration in rats. International J. Neuropsychopharmacology, 16: 913-918, 2013.
- Guidotti G., Calabrese F., Anacker C., Racagni G., Pariante C. and Riva M.A. Glucocorticoid receptor and FKBP5 are altered following exposure to chronic stress: modulation by antidepressant treatment. Neuropsychopharmacology, 38:616–627, 2013.
- GiovanoliS., Engler H., Engler A., RichettoJ. VogetM., Willi R., WinterC., Riva M.A., Mortensen P.B., SchedlowskiM. and Meyer U. Stress in puberty unmasks latent neuropathological consequences of prenatal immune activation in mice. Science 339 (6123):1095-1099, 2013.
- Anacker C., Cattaneo A., Musaelyan K., Zunszain P.A. Horowitz M., Molteni R., Luoni A., Calabrese F., Tansey K., Gennarelli M., Thuret S., Price J., Uher R., Riva M.A., Pariante C.M. A novel role for the kinase SGK1 in stress, depression, and glucocorticoid effects on hippocampal neurogenesis. Proc. Natl. Acad Sci USA, 110:8708-13, 2013.
- Molteni R., Macchi F., Zecchillo C., Dell'Agli M., Colombo E., Calabrese F., Guidotti G., Racagni G., Riva M.A. Modulation of the inflammatory response in rats chronically treated with the antidepressant agomelatine. Eur Neuropsychopharmacol. Epub, 2013.
- Richetto J., Calabrese F., Racagni G., Riva M.A. and Meyer U. Prenatal Immune Activation Induces Maturation-Dependent Alterations in the Prefrontal GABAergic Transcriptome. Schizophrenia Bulletin, 2013 in press.