Biology subjects

Franchini, D.

Publications and source records attributed to Franchini, D..

3 recordsLinked to original sources

bioRxiv2026

MFF SUMOylation regulates neuronal mitochondrial morphology and facilitates AMPK-induced mitochondrial fragmentation

Mitochondrial dysfunction and fragmentation in neurons are characteristics of many neurodegenerative conditions. AMP-activated protein kinase (AMPK) is a cellular energy sensor which is hyperactivated in Alzheimers disease. Under stress conditions, AMPK-mediates phosphorylation of the outer mitochondrial membrane protein mitochondrial fission factor (MFF), leading to SUMOylation at Lys151. MFF SUMOylation promotes fission and subsequent mitochondrial fragmentation. Here, using primary neuronal culture, we investigate the role of MFF SUMOylation in mitochondrial morphology and function. We show that MFF SUMOylation is required to maintain neuronal mitochondrial length under basal conditions in axons and dendrites. Using the AMPK activator (AICAR) to induce mitochondrial fission, show that preventing MFF SUMOylation reduces AICAR-induced fragmentation of dendritic mitochondria. These findings reconcile observations of AMPK hyperactivation and mitochondrial fragmentation by revealing the AMPK-MFF-SUMO pathway to be crucial in neuronal mitochondrial fission.

neuroscience↗

bioRxiv2026

Region- and layer-specific glutamatergic synapse development in the nascent cortical hierarchy

Neocortical synapses are highly dynamic during brain development, undergoing formation, elimination, and maturation before acquiring properties that support adult cognition. Individual neocortical regions develop at different ages and individual layers within these regions contain distinct neuronal subtypes that process unique patterns of local and long-range synaptic input. To better understand the development of the cortical hierarchy we explored the laminar maturation of glutamatergic synapses across cortical regions. Synapse maturation was associated with the upregulation of the postsynaptic density protein PSD95. This maturation occurred in a region- and layer-specific manner -- layers associated with feedforward pathways develop earlier, while layers associated with higher-order circuits develop later. Our findings highlight adolescence as an important period for the cortex-wide maturation of synapses in cortical layer 1, synapses known to receive top-down feedback from higher-order cortices. We propose that this delayed adolescent maturation of top-down input represents a global signature of cortical development and seemingly acts as the final stage of outside-in brain maturation.

neuroscience↗

bioRxiv2023

Adolescent chronic sleep restriction promotes alcohol drinking in adulthood: evidence from epidemiological and preclinical data.

Epidemiological investigations have indicated that insufficient sleep is prevalent among adolescents, posing a globally underestimated health risk. Sleep fragmentation and sleep loss during adolescence have been linked to concurrent emotional dysregulation and an increase in impulsive, risk-taking behaviors, including a higher likelihood of substance abuse. Among the most widely used substances, alcohol stands as the primary risk factor for deaths and disability among individuals aged 15-49 worldwide. While the association between sleep loss and alcohol consumption during adolescence is well documented, the extent to which prior exposure to sleep loss in adolescence contributes to heightened alcohol use later in adulthood remains less clearly delineated. Here, we analyzed longitudinal epidemiological data spanning 9 years, from adolescence to adulthood, including 5497 participants of the Avon Longitudinal Study of Parents And Children cohort. Sleep and alcohol measures collected from interviews and questionnaires at 15 and 24 years of age were analyzed with multivariable linear regression and a cross-lagged autoregressive path model. Additionally, we employed a controlled preclinical experimental setting to investigate the causal relationship underlying the associations found in the human study and to assess comorbid behavioral alterations. Preclinical data were collected by sleep restricting Marchigian Sardinian alcohol preferring rats (msP, n=40) during adolescence and measuring voluntary alcohol drinking concurrently and in adulthood. Polysomnography was used to validate the efficacy of the sleep restriction procedure. Behavioral tests were used to assess anxiety, risky behavior, and despair. In humans, after adjusting for covariates, we found a cross-sectional association between all sleep parameters and alcohol consumption at 15 years of age but not at 24 years. Notably, alcohol consumption (Alcohol Use Disorder Identification Test for Consumption) at 24 years was predicted by insufficient sleep at 15 years whilst alcohol drinking at 15 years could not predict sleep problems at 24. In msP rats, adolescent chronic sleep restriction escalated alcohol consumption and led to increased propensity for risk-taking behavior in adolescence and adulthood. Our findings demonstrate that adolescent insufficient sleep causally contributes to higher adult alcohol consumption, potentially by promoting risky behavior.

neuroscience↗