Biology subjects

D'Agostino, A.

Publications and source records attributed to D'Agostino, A..

4 recordsLinked to original sources

bioRxiv2024

Striatal output regulates the postnatal maturation of cortical circuits

The dorsomedial prefrontal cortex (dmPFC) is interconnected with the basal ganglia (BG) through large-scale circuit loops that regulate critical motor and cognitive functions. In mice, these circuits undergo extensive postnatal maturation with marked changes in neural activity and expansion of synaptic connectivity. While cortical activity is known to regulate the development of downstream striatal circuits, the role of the basal ganglia in cortical maturation remains unknown. Here, we used mesoscale two-photon microscopy and whole-cell electrophysiology to examine whether striatal output during early postnatal development impacts the activity and maturation of upstream dmPFC circuits. We found that ablating spiny projection neurons of the direct or indirect pathways of the striatum during the first two postnatal weeks causes bidirectional changes in dmPFC neural activity, similar to observations in mature circuits. In addition, these manipulations alter the maturation of synaptic connectivity of dmPFC layer 2/3 pyramidal neurons, shifting the balance of excitation and inhibition of cortical circuits. These findings demonstrate that striatal output modulates the activity of cortical circuits during early postnatal development and suggest a regulatory role of the basal ganglia in the establishment of cortical circuits.

neuroscience↗

bioRxiv2024

Generation and benchmarking of a collection of hiPSC lines from Schizophrenia Patients with Diverse Clinical Profiles

Limited therapeutic advancements in Schizophrenia (SCZ) depend on the heterogeneous nature of the disorder, impacting drug development and clinical trials that assume uniform therapy response, neglecting individual genetic and epigenomic variability. Disease modeling using human induced pluripotent stem cells (hiPSCs) is ideally suited for precision medicine, enabling individualized treatment approaches. Here, we describe the generation of patient-specific lines from somatic cells of SCZ individuals with well-defined diverse clinical trajectories using a Sendai virus-based reprogramming system. Karyotypically and CGH-array validated, the generated hiPSCs expressed diagnostic markers and demonstrated functional pluripotency. Converting these hiPSCs into neural progenitor cells enables the identification of aberrant cellular phenotypes associated with specific pathologically relevant neural phenotypes. This collection of hiPSC lines serves as a platform for developing therapeutic compounds targeting neural populations, potentially addressing early-stage disease alterations.

neuroscience↗

bioRxiv2022

The bacterial lysate Lantigen B reduces the expression of ACE2 on primary oropharyngeal cells

Angiotensin-converting enzyme2 (ACE2) is the main cell surface receptor of the SARS-CoV-2 spike protein and is expressed in a variety of cell types, including cells of the respiratory tract. A bacterial lysate used for the prophylaxis of respiratory infections (OM-85), was recently shown to downregulate the expression of ACE2 in epithelial cells, suggesting its possible role as a prophylaxis of the onset of COVID19. Another bacterial lysate (Lantigen B, administered sublingually) is used in the prophylaxis of recurrent respiratory tract infections. It contains antigens obtained by chemical lysis from the most representative microbes of the respiratory tract. In this in vitro study, the capacity of Lantigen B to decrease ACE2 in human oropharyngeal cells was evaluated. The study was carried out in 40 healthy donors undergoing oropharyngeal swab for routine SARS-CoV-2 detection. Cells were treated in vitro with a 1:2 of Lantigen B. ACE2 expression was evaluated using a fluorescent anti-ACE2 monoclonal antibody and flow cytometry. A reduction in the number of positive cells was observed in 72% of the patients, while a modulation of ACE2 expression was observed in 62% of the samples. As a control, the expression of the CD54 rhinovirus receptor in the same cells was unaffected. To evaluate the functional effects of down regulation, in a subset of samples, the same oropharynx cells were incubated with Lantigen B and infected with wild-type SARS-CoV-2. After 24 hours, viral RNA, as assessed by rt-PCR, was significantly lower in samples treated with Lantigen B. In conclusion, this study demonstrates that Lantigen B, at a pharmacological dose, modulates the expression of the main SARS-CoV-2 receptor in oropharyngeal cells, and reduces viral yield. This activity could be synergistic with other approaches (vaccination and therapy) by reducing the number of potentially infected cells and thus reducing the effects of SARS-CoV-2 infection.

cell biology↗

bioRxiv2021

Wild cereal grain consumption among Early Holocene foragers of the Balkans predates the arrival of agriculture

Forager focus on wild cereal plants has been documented in the core zone of domestication in southwestern Asia, while evidence for forager use of wild grass grains remains sporadic elsewhere. In this paper, we present starch grain and phytolith analyses of dental calculus from 61 Mesolithic and Early Neolithic individuals from five sites in the Danube Gorges of the central Balkans. This zone was inhabited by likely complex Holocene foragers for several millennia before the appearance of the first farmers [~]6200 cal BC. We also analyzed forager ground stone tools for evidence of plant processing. Our results based on the study of dental calculus show that certain species of Poaceae (species of the genus Aegilops) were used since the Early Mesolithic, while ground stone tools exhibit traces of a developed grass grain processing technology. The adoption of domesticated plants in this region after [~]6500 cal BC might have been eased by the existing familiarity with wild cereals.

ecology↗