Projects

Matrix Metalloproteinase-9 and PeriNeuronal Nets: new therapeutic targets for Fragile X Syndrome
2023-2025 | PRIN Italian Ministry of University and Research

The project aims to expand current knowledge about the phenotype-genotype correlation in Fragile X syndrome (FXS) and to identify the perineuronal nets (PNNs) of the matrix and the enzymes that degrade them(MMP-9) as new extra-neuronal molecular targets . PNNs are key regulators of neuronal plasticity and of the excitation-inhibition balance and alteration of this balance is at the basis of FXSsymptomatology.The proposed strategy allows for preclinical evaluation of new treatments for FXS at different developmental stages , to carefully choose the best phase in which to intervene therapeutically.
The project also involves Prof Tempia's group (NICO) and ProfCarulli(Netherlands Institute for Neuroscience) and the Research Units of ProfChiurazzi and Prof Altieri(Università Cattolica del Sacro Cuoreand Università degliStudi di ROMA "La Sapienza", respectively).

New therapeutic perspectives in the treatment of X-fragile syndrome
2020-2022 | Fondazione CRT

Coordinator: Carola Eva Lab. - Project partner: 1) Prof. Benedetto Vitiello, Struttura Complessa di Neuropsichiatria Infantile dell’Ospedale Regina Margherita; 2) Dott. Marco Cambiaghi, laboratorio di Neurobiologia del Dipartimento di Neuroscienze, Biomedicina e Movimento, Università di Verona; 3) Prof.ssa Daniela Carulli, laboratorio di Neuroregenerazione dell’Istituto di Neuroscienze di Amsterdam; 4) Dott.ssa Annalisa Bianchini, Associazione Sezione Piemonte Sindrome X-Fragile

This project aims to study a possible molecular target for the development of innovative therapies for fragile X syndrome (FXS), a rare genetic disease of the autistic spectrum associated with intellectual disability. Despite the significant incidence, FXS syndrome is still poorly understood and underdiagnosed, while early and timely diagnosis is essential for patients and their families. To date, there is no approved therapy for FXS and only drugs that partially mitigate its symptoms are used. The research aims to: (i) Study the development and functioning of brain PNNs in a mouse model of X-fragile syndrome (Fmr1ko mice); (ii) Use the model to identify new drugs to prevent and correct functional deficits in children and adults with FXS, autism or other neurodevelopmental disorders; (iii) Identify critical periods in brain circuit development when drug therapy can be more effective.

Influence of maternal behaviour on the expression of brain plasticity brakes: a role in the susceptibility to anxiety?
2015-2017 | Research Project, University of Torino - Compagnia di San Paolo

Carola Eva co-PI with Daniela Carulli, NICO

The present project aims to unravel a new regulatory mechanism for neuronal plasticity that might underlie a wide range of psychopathologies and to reveal new targets for therapeutic interventions in stress and anxiety-related disorders. We shall combine diverse expertise from neurobiology, glycobiology, soft matter physics and neurophysiology to study if maternal care affects perineuronal nets (PNN) chemical/physical features in the limbic system, thereby influencing neuronal communication within specific networks and, in turn, anxiety. We will further challenge the function of limbic Npy1r mediated signaling in maternal care modulation of structural plasticity.

Complex mechanisms underlying permanent effects of perinatal environment  on synaptic plasticity  and susceptibilty to psychopathologies: from molecules to tissue properties to behaviour
2014-2015| Fondazione CRT

Carola Eva co-PI with Daniela Carulli and Annalisa Buffo, NICO

This project aims to test if maternal behavior leaves a signature on perineuronal nets (PNN)/myelin assembly, impacting the refinement of circuits involved in anxiety and stress resilience. We shall study if maternal environment affects the chemical and physical features of PNN and myelin development in the limbic system; and if these changes alter neural circuitry, generating anxiety in adults.
We shall also test if PNN modulation or enriched experience will rescue anxiety. Connecting molecular interactions and matrix properties to behaviour, our study will offer mechanistic insight into the role of plasticity modulators in inducing anxiety in early-life stressed mice.

A novel hypothesis on the development of metabolic syndrome in women
2014-2016 | Fondazione Cariplo

The final goals of this proposal are:

•  to demonstrate the extent to which ovarian estrogens and liver ERs are responsible for the increased incidence of MetS observed in women after menopause;
•  to identify potential mechanisms and the role of brain NPY-Npy1r system in this phenomenon;
•  to evaluate the negative or positive effects of specific dietary regimens in females with impaired ovarian functions.

This is a collaborative study that will enable to exploit the most appropriate pharmacological and genetic tools developed in our teams to verify the extent to which specific hepatic factors, as a consequence of ovarian failure and under specific dietary constrains, are able to influence the central nervous system (activity of the NPY-Npy1r system in a mouse model well suited to underline the different vulnerability to MetS of the two sex) and in WAT, liver and muscle. Our study might open the way to the generation of an entire class of novel Estrogen Receptor Modulators to be used for the therapy of MetS.

Effect of substances of abuse, psychoactive drugs, stress and maternal care on brain development and vulnerability to psychopathology
2011-2016 | 2010-2011 PRIN Italian Ministry of University and Research

The goal of this study is to uncover molecular mechanisms through which maternal care permanently affects limbic Npy1r gene expression and its specific contribution to vulnerability to psychopathologies in response to environmental factors, such as acute stress and ethanol exposure.  We aim to identify neuronal signaling pathways which interact with limbic Y1R in the regulation of:  1) neuronal plasticity in the limbic regions 2) behavioral, neurochemical and neuroendocrine responses to acute stress and ethanol consumption of mice with low expression of limbic Y1R. Finally, we will investigate whether non-pharmacological  or pharmacological treatments may reverse the effects of maternal care on limbic Y1R and related behaviors in adulthood. A greater understanding of these mechanisms may eventually allow specific therapeutic interventions, with a favorable impact on the vulnerability to anxiety disorders and ethanol abuse in adulthood.