Biology subjects

Papa, M.

Publications and source records attributed to Papa, M..

4 recordsLinked to original sources

bioRxiv2025

Mapping glioblastoma spreading: connexin43 and glial dynamic in mouse and human glioblastoma microenvironment

High-grade gliomas (HGGs), including astrocytoma and glioblastoma (GBM), constitute the most prevalent primary tumors of the central nervous system (CNS). GBM cells demonstrate a notable ability to infiltrate the brain parenchyma, precluding complete surgical resection. Here we investigated the spreading of GBM cells and the response of the CNS microenvironment focusing on glial cells, which are essential interactors to GBM. We used acute and organotypic slices from the mouse brain and peritumoral cortex of patients with HGGs. We found that human peritumoral tissue from cortical resection was characterized by high levels of the astrocytic Connexin43 protein (Cx43) and discrete infiltration of microglia. In contrast, the tumor core exhibited high myeloid infiltration and an altered extracellular matrix (ECM) composition, which was poor in CD44. We tracked mouse and primary human-labeled-GBM cells in 2D cultures and in co-culture with organotypic slices generated from mouse brain and human peritumoral tissues. We found that the implanted GBM cells infiltrated the brain tissue, implying early glial modifications including an increase in Cx43 expression and distribution. Furthermore, the blockage of Cx43 hemichannels was accompanied by morphological changes and polarization of human GBM cells, typical for migration phenomena. The present study sheds light on the dynamics of GBM cells spreading in the living brain tissue, suggesting that the progression of the tumor correlates with changes within the host brain. Our findings identify the upregulation of Cx43 expression as a highly consistent modification in both mouse and human tissue that may be crucial for GBM infiltration.

neuroscience↗

bioRxiv2024

Regional Microglial Response in Enthorino-hippocampal Slice Cultures to Schaffer Collateral Lesion and Metalloproteinases Modulation.

Microglia and astrocytes are essential in sustaining physiological networks on the central nervous system, with their ability to remodel the extracellular matrix, being pivotal for synapse plasticity. Recent findings challenge the traditional view of homogenous glial populations in the brain, uncovering morphological, functional and molecular heterogeneity among glial cells. This diversity has significant implications for both physiological and pathological brain states. In the present study, we mechanically induced a Schaffer collateral lesion (SCL) in mouse enthorino-hippocampal slice cultures to investigate glial behavior, i.e., microglia and astrocytes, under metalloproteinases (MMPs) modulation in the lesioned area, CA3, and the denervated region, CA1. We observed distinct response patterns in microglia and astrocytes 3 days after the lesion. Notably, GFAP-expressing astrocytes showed no immediate changes post-SCL. Microglia responses varied depending on their anatomical location. The MMPs inhibitor GM6001 did not affect microglial reactions in CA3, while increasing the Iba1 cells numbers in CA1, underscoring the complexity of the hippocampal neuroglial network post-injury. These findings highlight the importance of understanding glial regionalization following neural injury and MMPs modulation, and pave the way for further research into glia-targeted therapeutic strategies for neurodegenerative disorders.

neuroscience↗

bioRxiv2020

Clinical Epidemiology of congenital heart diseases in dogs: prevalence, popularity and volatility throughout twenty years of clinical practice

The epidemiology of Congenital Heart Diseases (CHDs) has changed over the past twenty years. We evaluated the prevalence of CHDs in the population of dogs recruited in a single referral center (RC); compared the epidemiological features of CHDs in screened breeds (Boxers) versus nonscreened (French and English Bulldogs and German Shepherds), investigated the association of breeds with the prevalence of CHDs, determined the popularity and volatility of breeds over a 20-year period; and analysed the trends of the most popular breeds in the overall population of new-born dogs registered in the Italian Kennel Club from 1st January 1997 to 31st December 2017. This was a retrospective observational study, the cardiological database of the RC was analysed, and 1,779 clinical records fulfilled the inclusion criteria. Descriptive statistics and frequencies regarding the most representative breeds and CHDs were generated. A logistic regression model was used to analyse the trends of the most common CHDs found in single breeds (French Bulldog, English Bulldog, Boxer, and German Shepherd), and in groups of breeds (brachycephalic breeds and the most represented large breeds). The relationships between the breed popularity and the presence of CHDs was studied. The most common CHDs were Pulmonic Stenosis (34,1%), Patent Ductus Arteriosus (26,4%), Subaortic Stenosis (14,6%), Ventricular Septal Defect (4,8%), Aortic Stenosis (4,7%), Tricuspid Dysplasia (3,4%), Atrial Septal Defect (1,9%), Double Chamber Right ventricle (1,8%), Mitral Dysplasia (1,6%), and reverse Patent Ductus Arteriosus (0,7%). The most represented pure breeds were Boxer (19,4%), German Shepherd (9,4%), French Bulldog (6,2%), English Bulldog (4,9%), Maltese (3,7%), Newfoundland (3,1%), Rottweiler (3,1%), Golden Retriever (3,0%), Chihuahua (2,8%), Poodle (2,5%), Cavalier King Charles Spaniel (2,2%), American Staffordshire Terrier (2,1%), Labrador Retriever (2,3%), Dobermann (2,1%), Miniature Pinscher (2,0%), Cocker Spaniel (2,0%), Yorkshire Terrier (1,7%), Dogue de Bordeaux (1,6%), Dachshund (1,6%), and Bull Terrier (1,5%). Chihuahuas, American Staffordshire Terriers, Border Collies, French Bulldogs, and Cavalier King Charles Spaniel were the most appreciated small and medium breeds, all of which showed a high value of volatility. In conclusion, this study found evidence for the value of the screening program implemented in Boxers, which decreased the prevalence of Subaortic Stenosis and Pulmonic Stenosis. However, fashions and trends influence dog owners choices more than the worries of health problems frequently found in a breed. Effective breeding programs are needed in order to control the diffusion of CHDs without impoverishing the genetic pool; in addition, dog owners should be educated, and the breeders supported by a network of veterinary cardiology centers.

pathology↗

bioRxiv2019

Design principles of ROS dynamic networks relevant to precision therapies for age-related diseases

The eminently complex regulatory network protecting the cell against oxidative stress, surfaces in several disease maps, including that of Parkinsons disease (PD). How this molecular networking achieves its various functionalities and how processes operating at the seconds-minutes time scale cause a disease at a time scale of multiple decennia is enigmatic.\n\nBy computational analysis, we here disentangle the reactive oxygen species (ROS) regulatory network into a hierarchy of subnetworks that each correspond to a different functionality. The detailed dynamic model of ROS management obtained integrates these functionalities and fits in vitro data sets from two different laboratories.\n\nThe model shows effective ROS-management for a century, followed by a sudden systems collapse due to the loss of p62 protein. PD related conditions such as lack of DJ-1 protein or increased -synuclein accelerated the systems collapse. Various in-silico interventions (e.g. addition of antioxidants or caffeine) slowed down the collapse of the system in silico, suggesting the model may help discover new medicinal and nutritional therapies.

systems biology↗