Biology subjects

Dotti, C. G.

Publications and source records attributed to Dotti, C. G..

3 recordsLinked to original sources

bioRxiv2026

Stable Vesicle-Associated BDNF from Embryonic and Young Cortical Extracellular Vesicles

In this work we show that small extracellular vesicles (sEVs) from embryonic mouse cortex or from cultured embryonic cortical neurons contain high levels of BDNF and sustain TrkB-dependent neuroprotective signaling. By contrast, sEVs from aged cortex are depleted of BDNF, and cells lacking active TrkB fail to mount a protective response when exposed to the same sEVs. Biochemical fractionation and trypsin sensitivity assay indicate that BDNF is a constitutive EV component and is exposed on or tightly associated with the vesicle surface--an arrangement that likely increases local ligand density. In a stability assay, EV-associated BDNF retained activity longer than soluble BDNF. Together, our findings suggest that many developmental effects of BDNF may be mediated by EVs, that impaired stress responses in the aged brain could reflect reduced formation of BDNF-containing EVs, and that embryonic sEVs may provide a more efficient vehicle for BDNF delivery than current therapeutic approaches.

molecular biology↗

bioRxiv2023

LOSS OF CLDN5 -AND INCREASE IN IRF7- IN THE HIPPOCAMPUS AND CEREBRAL CORTEX OF DIABETIC MICE AT THE EARLY SYMPTOMATIC STAGE.

Analyzing changes in gene expression within specific brain regions of individuals with Type 2 Diabetes (T2DM) who do not exhibit significant cognitive deficits can yield valuable insights into the mechanisms that may underlie the progression toward a more severe phenotype, for example as when individuals age. Here, we present evidence that adult mice with long-term type 2 diabetes mellitus (T2DM) and minor cognitive deficits display alterations in the expression of 27 genes in the cerebral cortex and 16 genes in the hippocampus compared to non-T2DM mice. Only six of these genes undergo the same type of change both in the cortex and hippocampus: Interferon regulatory factor 7 (Irf7), Hypoxia-inducible factor 3 alpha (Hif-3), period circadian clock 2 (Per2), xanthine dehydrogenase (Xdh), and Transforming growth factor {beta}-stimulated clone 22/TSC22 (Tscd3) are all upregulated, while Claudin-5 (Cldn5) is downregulated. At the protein level, Claudin5 and IRF7 showed equivalente changes: downregulation of CLDN5 and upregulation of IRF7. These results suggest that cognitive deficits linked to chronic T2DM may stem from compromised blood-brain barrier integrity and an abnormal inflammatory response in the early stages of the disease. This underscores the potential for therapeutic interventions targeting CLDN5 and IRF7.

neuroscience↗

bioRxiv2018

Radial F-actin Organization During Early Neuronal Development

The centrosome is thought to be the major neuronal microtubule-organizing center (MTOC) in early neuronal development, producing microtubules with a radial organization. In addition, albeit in vitro, recent work showed that isolated centrosomes could serve as an actin-organizing center (Farina et al., 2016), raising the possibility that neuronal development may, in addition, require a centrosome-based actin radial organization. Here we report, using super-resolution microscopy and live-cell imaging, F-actin organization around the centrosome with dynamic F-actin aster-like structures with F-actin fibers extending and retracting actively. Photoconversion/photoactivation experiments and molecular manipulations of F-actin stability reveal a robust flux of somatic F-actin towards the cell periphery. Finally, we show that somatic F-actin intermingles with centrosomal PCM-1 satellites. Knockdown of PCM-1 and disruption of centrosomal activity not only affect F-actin dynamics near the centrosome but also in distal growth cones. Collectively the data show a radial F-actin organization during early neuronal development, which might be a cellular mechanism for providing peripheral regions with a fast and continuous source of actin polymers; hence sustaining initial neuronal development.

neuroscience↗