RT journal article
T1 Glycogen Synthase Kinase‑3β Inhibitor VP3.15 Ameliorates Neurogenesis, Neuronal Loss and Cognitive Impairment in a Model of Germinal Matrix‑intraventricular Hemorrhage of the Preterm Newborn
A1 Atienza Navarro, Isabel
A1 Marco Delgado, Ángel José del
A1 Alves Martinez, Pilar
A1 García Pérez, María de los Ángeles
A1 Raya Marín, Álvaro
A1 Benavente Fernández, Isabel
A1 Gil, Carmen
A1 Martínez, Ana
A1 Lubián López, Simón Pedro
A1 García Alloza, Mónica
A2 BiomedicinaBiotecnología y Salud Pública
A2 Materno-Infantil y Radiología
K1 Preterm newborn
K1 Germinal matrix-intraventricular hemorrhage
K1 VP3.15
K1 Neurodegeneration
K1 Neurogenesis
K1 Cognition
AB Advances in neonatology have significantly reduced mortality rates due to prematurity. However, complications of prema-turity have barely changed in recent decades. Germinal matrix-intraventricular hemorrhage (GM-IVH) is one of the mostsevere complications of prematurity, and these children are prone to suffer short- and long-term sequelae, including cerebralpalsy, cognitive and motor impairments, or neuropsychiatric disorders. Nevertheless, GM-IVH has no successful treatment.VP3.15 is a small, heterocyclic molecule of the 5-imino-1,2,4-thiadiazole family with a dual action as a phosphodiesterase 7and glycogen synthase kinase-3β (GSK-3β) inhibitor. VP3.15 reduces neuroinflammation and neuronal loss in other neuro-degenerative disorders and might ameliorate complications associated with GM-IVH. We administered VP3.15 to a mousemodel of GM-IVH. VP3.15 reduces the presence of hemorrhages and microglia in the short (P14) and long (P110) term.It ameliorates brain atrophy and ventricle enlargement while limiting tau hyperphosphorylation and neuronal and myelinbasic protein loss. VP3.15 also improves proliferation and neurogenesis as well as cognition after the insult. Interestingly,plasma gelsolin levels, a feasible biomarker of brain damage, improved after VP3.15 treatment. Altogether, our data supportthe beneficial effects of VP3.15 in GM-IVH by ameliorating brain neuroinflammatory, vascular and white matter damage,ultimately improving cognitive impairment associated with GM-IVH
PB Springer
SN 1868-4483
YR 2024
FD 2024-01-17
LK http://hdl.handle.net/10498/31858
UL http://hdl.handle.net/10498/31858
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 10-nov-2026