Laboratory of Psycopharmacology and Molecular Psychiatry
The primary research goal of the laboratory is the investigation of the molecular mechanisms that might be disrupted in psychiatric illnesses, including depression and schizophrenia, 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 goals of our studies are:
- Molecular, functional and behavioral characterization of animal models for psychiatric disorders (primarily depression and schizophrenia), based on genetic (genes related to the serotoninergic system) or environmental manipulations (with a major focus on the role of neurodevelopment in shaping the susceptibility to mental illness).
- Identification of the molecular underpinnings of stress response and their role in the susceptibility or resilience to psychopathology.
- Characterization of the epigenetic mechanisms (DNA methylation and miRNA expression) for the long-term dysfunction associated with psychiatric disorders.
- Analysis of molecular mechanisms underlying the action of psychotropic drugs, focusing on different molecular players relevant for specific domains (Anhedonia, cognition etc.) that are disrupted in psychiatric conditions, including neuroplastic markers, neurotransmission (glutamatergic and GABAergic), HPA axis functionality and responsivity to glucocorticoids, inflammation and redox mechanisms.
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 drugs used. To this end, several biochemical and cell/molecular biological techniques are employed.
- Epigenetic analysis through Chromatin immunoprecipitation to study histone post-translational modifications and DNA-methylation alterations of target genes
- whole-genome analysis
Gene espression analysis (mRNA):
- Real time PCR
- Western blotting
- Immunostaining of brain tissue and confocal microscopy
Genetic model of depression (rat)
- Tph2 Knockout
- Sert Knockout
Environmental Model of susceptibility to neuropsychiatric disorders (rat):
- Prenatal Restraint Stress
- Unpredictable chronic mild stress
Behavioral test to evaluate the presence of core symptoms related to:
- Depression/ Anhedonia
- Cognitive function
- Social function
- Prof. Peter Gass, Interdisciplinary Center for Neurosciences – Mannheim (Germany)
- Dr. Rodrigo Grassi-Oliveira, Pontifícia Universidade Católica do Rio Grande do Sul – Porto Alegre (Brasil)
- Prof. Raffaella Molteni, University of Milan – Milan (Italy)
- Prof. Mariusz Papp, Institute of Pharmacology of the Polish Academy of Sciences – Cracovia (Poland)
- Prof. Carmine Pariante, Institute of Psychiatry at King's College – Londra (UK)
- Dr. Natalia Alenina, Max-Delbrück-Center for Molecular Medicine (MDC), Berlin (Germany)
- Prof. Judith R. Homberg, Department of Cognitive Neuroscience, Centre for Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen (The Netherlands)
Selected publications (max 5)
1. Caraci F, Calabrese F, Molteni R, Bartova L, Dold M, Leggio GM, Fabbri C, Mendlewicz J, Racagni G, Kasper S, Riva MA, Drago F (2018). International Union of Basic and Clinical Pharmacology CIV: The Neurobiology of Treatment-resistant Depression: From Antidepressant Classifications to Novel Pharmacological Targets. Pharmacol Rev. 70:475-504.
2. Cattaneo A, Cattane N, Malpighi C, Czamara D, Suarez A, Mariani N, Kajantie E, Luoni A, Eriksson JG, Lahti J, Mondelli V, Dazzan P, Räikkönen K, Binder EB, Riva MA, Pariante CM (2018). FoxO1, A2M, and TGF-β1: three novel genes predicting depression in gene X environment interactions are identified using cross-species and cross-tissues transcriptomic and miRNomic analyses. Mol Psychiatry. 2018 Jan 4.
3. Calabrese F, Brivio P, Gruca P, Lason-Tyburkiewicz M, Papp M, RivaMA (2017). Chronic Mild Stress-Induced Alterations of Local Protein Synthesis: A Role for Cognitive Impairment. ACS Chem Neurosci. 8:817-825.
4. Luoni A., Massart R., Nieratschker V. Nemoda Z., Blasi G., Gilles M., Witt S.H., Suderman M.J., Suomi S-J., Porcelli A., Rizzo G., Fazio L., Torretta S., Rampino A., Berry A., Gass P., Cirulli F., Rietschel M., Bertolino A., Deuschle M., Syzf M. and Riva M.A. Ankyrin-3 as a Molecular Marker of Early Life Stress. Translational Psychiatry6: e943; doi:10.1038, 2016.
5. Calabrese F, Guidotti G, Middelman A, Racagni G, Homberg J, RivaMA (2013). Lack of serotonin transporter alters BDNF expression in the rat brain during early postnatal development. Mol Neurobiol. 48:244-56.