Biology subjects

Leo, M.

Publications and source records attributed to Leo, M..

4 recordsLinked to original sources

bioRxiv2026

Age-dependent peripheral nerve and Schwann cell abnormalities in a mouse model of late-onset spinal muscular atrophy

Spinal muscular atrophy (SMA) is increasingly recognized as a multisystem disorder involving non-neuronal cells, yet the role of Schwann cells (SCs) in late-onset SMA (loSMA) remains unclear. We investigated age-dependent peripheral nerve pathology in a four-copy SMN2 mouse model of loSMA. Sciatic nerves from wild-type and loSMA mice were analyzed at postnatal (P) days 20, 35, 70, and >100 using semi-thin morphometry, immunofluorescence for MBP, Sox10, Sox2, and F4/80, and nerve conduction studies. loSMA nerves showed reduced myelin thickness at all time points and smaller axon diameters at P20 and P35. G- ratios were reduced at P20 but increased from P35 onward, indicating progressively altered axon-myelin relationships. MBP immunofluorescence intensity, compound muscle action potential amplitude, and nerve conduction velocity were reduced in loSMA mice at P>100. The proportion of Sox2+ SCs increased from P35 onward, while Sox10+ cell abundance increased at later stages. F4/80+ macrophages were transiently elevated at P35 and correlated with Sox2+ cell numbers at this stage. These findings demonstrate age-dependent myelin abnormalities, altered SC states, and transient accumulation of macrophages in loSMA peripheral nerves. Whether these changes are SC-autonomous or secondary to chronic axonal dysfunction remains to be determined.

neuroscience↗

bioRxiv2025

Restoration of ovarian endocrine function with encapsulated immune isolated human ovarian xenograft in ovariectomized mice

Anti-cancer treatments cause premature depletion of the non-renewable ovarian reserve of follicles, the source of key steroid hormones, leading to premature ovarian insufficiency (POI) in 50% of pediatric cancer survivors. Patients with POI, especially at the onset of pubertal development, experience significant endocrine complications, including delayed growth, elevated risks of obesity and diabetes, and accelerated cardiovascular, musculoskeletal and neurological disorders as adults. The only approved pharmacological treatment for POI is an off-label prescribed hormone replacement therapy, which does not replace physiologically functioning ovaries. To restore production of ovarian hormones and protect against immune-mediated injury, we developed a hydrogel-based capsule for implantation of donor ovarian tissue. We evaluated the restoration of ovarian endocrine function in ovariectomized immunodeficient (NOD scid gamma, NSG) mice implanted with encapsulated xenografts over 20 weeks through daily vaginal cytology, hormone measurements and histological analysis of explanted human xenografts. The encapsulated xenografts integrated into the murine hypothalamus-pituitary-gonad (HPG) axis responding to circulating murine gonadotropins and restoring ovarian endocrine function. As controls, we implanted non encapsulated human ovarian xenografts comparable in size. Without the need for exogeneous stimulation, the estrous cyclicity resumed in both groups of mice 12 weeks post implantation and all mice regularly cycled experiencing between 3 to 8 estrous cycles in 20 weeks. The levels of estradiol gradually increased reaching on average 50pg/mL 20 weeks post implantation. Morphological analysis of the encapsulated grafts revealed presence of large antral follicles, [~]3mm in diameter, consistent with regular cyclicity and measurable levels of circulating hormones. This work demonstrates that endocrine function of encapsulated human ovarian tissue was not affected by the encapsulation and integrated with the host physiology similarly to the non-encapsulated controls.

bioengineering↗

bioRxiv2023

Post-ischemic triiodothyronine treatment improves stroke outcome by stabilizing the blood-brain barrier

Thyroid hormones control a variety of processes in the central nervous system and influence its response to different stimuli, such as ischemic stroke. Post-stroke administration of triiodothyronine (T3) has been reported to substantially improve outcomes, but the optimal dosage and time window remain elusive. To this end we investigated the consequences of T3 treatment in an experimental model of ischemic stroke in mice. Our research demonstrated a dose-dependent protective effect of T3 by reducing infarct volumes, with the optimal T3 dosage identified as 25 {micro}g/kg. In addition, we observed a time-dependent effectiveness that was most pronounced when T3 was administered 1 h after transient middle cerebral artery occlusion, with a gradual reduction in efficacy at 4.5 h, and no reduction in infarct volumes when T3 was injected with an 8 h delay. This protective effect persisted for 72 h post-tMCAO, and had accelerated the recovery of motor function by day 3. In-depth investigations further revealed stabilization of the blood-brain barrier, indicated by reduced extravasation of Evans Blue and diminished aquaporin-4 expression, with reduced inflammation and less cell death as underlying reasons. Our findings suggest that thyroid hormones may be a promising intervention for clinical stroke.

neuroscience↗

bioRxiv2017

Pleistocene climate change and the formation of regional species pools

This preprint has been reviewed and recommended by Peer Community In Evolutionary Biology (https://doi.org/10.24072/pci.evolbiol.100053). Despite the description of bioregions dates back from the origin of biogeography, the processes originating their associated species pools have been seldom studied. Ancient historical events are thought to play a fundamental role in configuring bioregions, but the effects of more recent events on these regional biotas are largely unknown. We use a network approach to identify regional and sub-regional faunas of European Carabus beetles, and analyse the effects of dispersal barriers, niche similarities and phylogenetic history on their configuration. We identify a transition zone matching the limit of the ice sheets at Last Glacial Maximum. While southern species pools are mostly separated by dispersal barriers, in the north species are mainly sorted by their environmental niches. Strikingly, most phylogenetic structuration of Carabus faunas occurred during the Pleistocene. Our results show how extreme recent historical events -such as Pleistocene climate cooling, rather than just deep-time evolutionary processes, can profoundly modify the composition and structure of geographic species pools.

ecology↗