Venue: Centre Broca
Miriam Melis
University of Cagliari, Italy
https://www.miriammelislab.it/about/biography/
Invited by Mario Carta and Giovanni Marsicano
Title
Interference with developmental endocannabinoid signaling and psychopathological trajectories
Abstract
Multiple lines of preclinical and clinical evidence have shown that different environmental factors, such as infectious and chemical agents, stress, and psychosocial risk factors, contribute to heightened risk for developing neuropsychiatric disorders, especially those with neurodevelopmental origin. The developing brain exposed to insults responds with a series of adaptive responses altering its developmental trajectory, which may lead to subtle pre-clinical (endo)phenotypes that are susceptible to subsequent environmental challenges. Notably, the endocannabinoid system plays a key role in discrete developmental processes, including neurogenesis, glial formation, neuronal migration, axonal elongation, fasciculation, synaptogenesis and synaptic pruning. It is, therefore, pivotal to identify the conditions that alter the normal actions of endocannabinoids during formation and maturation of the brain, which are relevant to the derangement of proper developmental trajectories and confer vulnerability to psychopathologies. We use animal models of prenatal exposure to diverse xenobiotics, along with other environmental insults, which are regarded as predictive risk factors for the development of child psychopathology in order to decipher the underpinnings of prodromal phases of late-onset disorders, and to unveil potential endophenotypes. Deciphering neurobiological and psychopathological underpinnings of such endophenotypes may, therefore, offer opportunities to inform early prevention, diagnosis and intervention, particularly in the context of gender- and age- tailored interventions.
Key publications
– Serra V, Aroni A, Bortolato M, Frau R, Melis M (2023) Endocannabinoid-dependent decrease of GABAergic transmission on dopaminergic neurons is associated with susceptibility to cocaine stimulant effects in pre-adolescent male MAOA hypomorphic mice exposed to early life stress. Neuropharmacology 233:109548. doi: 10.1016/j.neuropharm.2023.109548.
– Santoni M, Sagheddu C, Serra V, Mostallino R, Castelli MP, Pisano F, Scherma F, Fadda P, Muntoni AL, Zamberletti E, Rubino T, Melis M, Pistis M (2023) Maternal immune activation impairs endocannabinoid signaling in the mesolimbic system of adolescent male offspring. Brain Behav Immun; S0889-1591(23)00027-2. doi: 10.1016/j.bbi.2023.02.002.
– Sagheddu C, Traccis F, Serra V, Congiu M, Frau R, Cheer JF, Melis M (2021) Mesolimbic dopamine dysregulation as a signature of information processing deficits imposed by prenatal THC exposure. Prog Neuro-psych Bio Psych, Volume 105, DOI: 10.1016/j.pnpbp.2020.110128
– 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. Nature Neuroscience. 22: 1975–1985; 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