Inhibition of GSK3β rescues hippocampal development and learning in a mouse model of CDKL5 disorder

• Published in: Neurobiology of disease Vol. 82; pp. 298 - 310
• Main Authors: Fuchs, Claudia, Rimondini, Roberto, Viggiano, Rocchina, Trazzi, Stefania, De Franceschi, Marianna, Bartesaghi, Renata, Ciani, Elisabetta
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2015; Elsevier
• Subjects: Animals; Apoptosis - drug effects; Apoptosis - physiology; CDKL5 disorder; Cell Survival - drug effects; Cell Survival - physiology; Disease Models, Animal; Encephalopathy; Glycogen Synthase Kinase 3 - antagonists & inhibitors; Glycogen Synthase Kinase 3 - metabolism; Glycogen Synthase Kinase 3 beta; GSK3β inhibitor; Hippocampus - drug effects; Hippocampus - enzymology; Hippocampus - growth & development; Hippocampus - pathology; Indoles - pharmacology; Learning Disabilities - drug therapy; Learning Disabilities - enzymology; Learning Disabilities - pathology; Male; Maleimides - pharmacology; Maze Learning - drug effects; Maze Learning - physiology; Mice, Knockout; Neural Stem Cells - drug effects; Neural Stem Cells - enzymology; Neural Stem Cells - pathology; Neurogenesis - drug effects; Neurogenesis - physiology; Neurology; Neurons - drug effects; Neurons - enzymology; Neurons - pathology; Neuroprotective Agents - pharmacology; Nootropic Agents - pharmacology; Pharmacotherapy; Protein Kinase Inhibitors - pharmacology; Protein Serine-Threonine Kinases - deficiency; Protein Serine-Threonine Kinases - genetics; Rescue of hippocampal developmental; Spatial Memory; Rescue of hippocampal developmental; Pharmacotherapy; GSK3β inhibitor; CDKL5 disorder; Encephalopathy

Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been identified in a rare neurodevelopmental disorder characterized by early-onset seizures, severe developmental delay, intellectual disability and Rett syndrome-like features. CDKL5 is highly expressed in the brain during e...