Biology subjects

Massa, F.

Publications and source records attributed to Massa, F..

5 recordsLinked to original sources

bioRxiv2025

Inhibition of eIF5A hypusination improves pancreatic islet transplantation outcomes by promoting ischemia tolerance

Pancreatic islet transplantation provides substantial benefits for individuals with Type 1 Diabetes (T1D). However, the low yield of the procedure limits its therapeutic potential, as multiple injections from different donors are needed to provide sufficient islets for a single recipient. Many islets are lost during preparation and transplantation, primarily due to ischemia/reperfusion injuries. GC7 (N1-guanyl-1,7-diaminoheptane), an inhibitor of eIF5A hypusination, improves the resistance of various cells to ischemia/reperfusion. Our study therefore explored whether ex-situ conditioning of pancreatic islets with GC7 during the preparation process could serve as a strategy to enhance the outcomes of pancreatic islet transplantation. Conditioning of mouse primary islets with GC7 at the digestion step of the pancreas significantly improved the procedure yield. Indeed, islets showed better survival at 24h and 72h after isolation and major protection against ischemia/reperfusion injury. Finally, the transplantation of a suboptimal number of islets under the renal capsule of hyperglycemic mice demonstrated superior functionality and survival of islets conditioned with GC7 compared to control islets. Collectively, these findings demonstrate that conditioning pancreatic islets with GC7 enhances their resistance to ischemia-reperfusion injury and significantly improves the efficiency of pancreatic islet transplantation. Hence the use of GC7 appears as a promising strategy to win one of the major challenges currently faced in the field of Type 1 diabetes.

cell biology↗

bioRxiv2024

Predicting Future Development of Stress-Induced Anhedonia From Cortical Dynamics and Facial Expression

The current state of mental health treatment for individuals diagnosed with major depressive disorder leaves billions of individuals with first-line therapies that are ineffective or burdened with undesirable side effects. One major obstacle is that distinct pathologies may currently be diagnosed as the same disease and prescribed the same treatments. The key to developing antidepressants with ubiquitous efficacy is to first identify a strategy to differentiate between heterogeneous conditions. Major depression is characterized by hallmark features such as anhedonia and a loss of motivation (1, 2), and it has been recognized that even among inbred mice raised under identical housing conditions, we observe heterogeneity in their susceptibility and resilience to stress (3). Anhedonia, a condition identified in multiple neuropsychiatric disorders, is described as the inability to experience pleasure and is linked to anomalous medial prefrontal cortex (mPFC) activity (4). The mPFC is responsible for higher order functions (5-8), such as valence encoding; however, it remains unknown how mPFC valence-specific neuronal population activity is affected during anhedonic conditions. To test this, we implemented the unpredictable chronic mild stress (CMS) protocol (9-11) in mice and examined hedonic behaviors following stress and ketamine treatment. We used unsupervised clustering to delineate individual variability in hedonic behavior in response to stress. We then performed in vivo 2-photon calcium imaging to longitudinally track mPFC valence-specific neuronal population dynamics during a Pavlovian discrimination task. Chronic mild stress mice exhibited a blunted effect in the ratio of mPFC neural population responses to rewards relative to punishments after stress that rebounds following ketamine treatment. Also, a linear classifier revealed that we can decode susceptibility to chronic mild stress based on mPFC valence-encoding properties prior to stress-exposure and behavioral expression of susceptibility. Lastly, we used a markerless pose tracking computer vision tool, SLEAP (31), to predict whether a mouse would become resilient or susceptible based on facial expressions during a Pavlovian discrimination task. These results indicate that mPFC valence encoding properties and behavior are predictive of anhedonic states. Altogether, these experiments point to the need for increased granularity in the measurement of both behavior and neural activity, as these factors can predict the predisposition to stress-induced anhedonia.

neuroscience↗

bioRxiv2020

Astroglial calcium transfer from endoplasmic reticulum to mitochondria determines synaptic integration

Intracellular calcium signaling underlies the astroglial control of synaptic transmission and plasticity. Mitochondria-endoplasmic reticulum contacts (MERCs) are key determinants of calcium dynamics, but their functional impact on astroglial regulation of brain information processing is currently unexplored. We found that the activation of astrocyte mitochondrial-associated CB1 receptors (mtCB1) determines MERCs-dependent intracellular calcium signaling and synaptic integration. The stimulation of mtCB1 receptors promotes calcium transfer from the endoplasmic reticulum to mitochondria through specific mechanisms regulating the activity of the mitochondrial calcium uniporter (MCU) channel. Physiologically, mtCB1-dependent mitochondrial calcium uptake determines the precise dynamics of cytosolic calcium events in astrocytes upon endocannabinoid mobilization. Accordingly, electrophysiological recordings in hippocampal slices showed that genetic exclusion of mtCB1 receptors or specific astroglial MCU inhibition blocks lateral synaptic potentiation, a key example of astrocyte-dependent integration of distant synapses activity. Altogether, these data reveal an unforeseen link between astroglial MERCs and the regulation of brain network functions.

neuroscience↗

bioRxiv2020

POMC neurons functional heterogeneity relies on mTORC1 signaling

Hypothalamic Pro-opiomelanocortin (POMC) neurons are classically known to trigger satiety. However, they encompass heterogeneous subpopulations whose functions are unknown. Here we show that POMC neurons releasing GABA, glutamate or both neurotransmitters possess distinct spatial distribution, molecular signatures and functions. Functional specificity of these subpopulations relies on the energy sensor mechanistic Target of Rapamycin Complex 1 (mTORC1), since pharmacological blockade of mTORC1, by mimicking a cellular negative energy state, simultaneously inhibited POMC/glutamatergic and activated POMC/GABAergic neurons. Chemogenetics and conditional deletion of mTORC1 then demonstrated that mTORC1 blockade in POMC neurons causes hyperphagia. This is due to decreased POMC-derived anorexigenic -melanocyte-stimulating hormone and the recruitment of POMC/GABAergic neurotransmission, which is restrained by cannabinoid type 1 receptor signaling. Genetic inhibition of glutamate release from POMC neurons also produced hyperphagia, recapitulating the phenotype caused by mTORC1 blockade. Altogether, these findings pinpoint the molecular mechanisms engaged by POMC neurons to oppositely control feeding, thereby challenging conventional views about their functions.

neuroscience↗

bioRxiv2019

Modeling in an oral health study through two statisticalmethods in Uruguay

In epidemiological studies it is common practice to work with binary variables that reflect the presence of certain diseases, which in turn may be associated with another set of variables, that in general are assumed as risk factors of the former. In the field of epidemiological studies referred to oral health, it is common to inquire about the relationship between the presence of some pathologies and certain characteristics of the study participants through generalized linear models (GLM). However, this type of analysis is usually carried out for each variable of interest separately and at no time is a measure obtained that summarizes the status of each participant. The objective was to apply and compare two methodologies; one applying classical approach of explaining each oral disease separately from a set of explanatory variables and another using item response theory (IRT) models (specifically the Rasch model) since they allow the joint analysis of a set of variables obtaining an individual assessment as a by-product, which in this case is interpreted as \"sickness proneness\". On the other hand, the analysis presented here extends the Rasch model including a linear predictor that allows to investigate about the possible effect of several factors on the propensity of the individuals to suffer the different pathologies. Our results found evidence of an effect of gender, insufficient physical activity (IPhA) and age on general proneness to oral diseases.

epidemiology↗