The aim of our research is to understand neurobiological underpinnings (e.g., adaptations of both mesocorticolimbic dopamine pathway and endocannabinoid system) of resilience and susceptibility to neuropsychiatric disorders (e.g., substance use disorder, antisocial behavior, anxiety, depression).
Whether or not these are innate (i.e., temperaments, sex) or induced by early life adverse events (e.g. drug exposure, adverse social events) will be thoroughly investigated via an integrative approach including cellular physiology, neuroanatomy, molecular and behavioral analysis.
This project is based upon my personal interest in neuropsychiatric disorders, which mirror affective imbalances within the brain. Affects are essential for well-being, and once primary physiological needs and safety are satisfied, interpersonal interaction and acceptance represent a need that has to be met, and drives motivation. In fact, they act as natural reinforcers, and are important for social and cognitive development.
The mesocorticolimbic dopamine system, key component of brain reward circuitry, processes value-related signals, and is considered an important circuit for affective functioning. Modulation of pathways determining the strength and direction of synaptic plasticity of such a system is, therefore, crucial in regulating experience-dependent behavioral changes, and viceversa. In particular, the individual response to early life adverse experience depends upon an organism’s innate biological make-up.
The findings will enable to develop new pharmacological strategies for the prevention and treatment of aberrant affective functioning, especially by investigating the mechanisms of resilience.
We began to address this issue by examining the role of sex and temperaments in cannabis and alcohol dependence, respectively, as well as in aggressiveness (see selected publications below).
Frau R, Miczán V, Traccis F, Aroni S, Pongor CI, Saba P, Serra V, Sagheddu C, Fanni S, Congiu M, Devoto P, Cheer JF, Katona I, Melis M (2019) Prenatal THC exposure produces a hyperdopaminergic phenotype rescued by pregnenolone Nat Neurosci. doi: 10.1038/s41593-019-0512-2.
Frau R, Fanni S, Serra V, Simola N, Godar SC, Traccis , Devoto P, Bortolato M, Melis M (2019) Dysfunctional mesocortical dopamine circuit at pre-adolescence is associated to aggressive behavior in MAO-A hypomorphic mice exposed to early life stress. Neuropharmacol. doi: 10.1016/j.neuropharm.2019.01.032
Melis M, Sagheddu C, De Felice M, Casti A, Madeddu C, Spiga S, Muntoni AL, Mackie K, Marsicano G, Colombo G, Castelli MP, Pistis M. (2014) Enhanced endocannabinoid-mediated modulation of rostromedial tegmental nucleus drive onto dopamine neurons in Sardinian alcohol-preferring rats. Journal of Neuroscience, 34(38):12716-24
Melis M, De Felice M, Lecca S, Fattore L, Pistis M (2013): Sex-specific tonic 2-arachidonoylglycerol signaling at inhibitory inputs onto dopamine neurons of Lister Hooded rats. Frontiers in Integrative Neuroscience, 7(93):1-13.
Bortolato M, Godar S, Melis M, Soggiu A, Roncada P, Casu A, et al. (2012) NMDA receptors mediate the role of monoamine oxidase A in pathological aggression. Journal of Neuroscience, 32(25):8574-82.
From letf: Dopamine (TH, green) neurons backfilled by including biocytin (red) in the recording pipette during whole cell patch clamp experiment. Current clamp traces of dopamine cell spontaneous activity (in red overlaid) and, on the right, DIC image of a putative dopamine neuron (*).
Neurotree @ http://neurotree.org/neurotree/tree.php?pid=17753&pnodecount=4&cnodecount=2&fontsize=1
Diagram illustrating the risk factors leading to an at-risk endophenotype for Substance Use Disorder (SUD). The interaction among biological make up of the individual, environment (e.g. one or both parental SUD, parental neglect, peer influence, etc) and age-related effects of indirect (i.e. pre/peri-natal exposure to drugs of abuse such as cannabis derivatives) and direct (early onset SUD, including CUD) results in epigenetic modifications and changes at cellular and synaptic level that contribute to the development of an at-risk endophenotype for SUD. Figure from: Melis et al. 2017 “New vistas on Cannabis Use Disorder”(Neuropharmacology, 124:62-72. doi: 10.1016/j.neuropharm.2017.03.033)
Benvenuti nel sito di Miriam Melis
- Professore Associato
- Area scientifico disciplinare:
- Scienze biologiche
- Settore scientifico disciplinare:
- BIO/14 FARMACOLOGIA
- Dipartimento di afferenza:
- Dipartimento di Scienze Biomediche
- Email email@example.com - Tel. 070/675-4322 -4340 fax: 070/675-4320
- Orario di ricevimento:
- Ricevo previo appuntamento via email