Luteolin Treatment Ameliorates Brain Development and Behavioral Performance in a Mouse Model of CDKL5 Deficiency Disorder

CDKL5 deficiency disorder (CDD), a rare and severe neurodevelopmental disease caused by mutations in the X-linked CDKL5 gene, is characterized by early-onset epilepsy, intellectual disability, and autistic features. Although pharmacotherapy has shown promise in the CDD mouse model, safe and effectiv...

Full description

Saved in:
Bibliographic Details
Published in:International journal of molecular sciences 2022-08, Vol.23 (15), p.8719
Main Authors: Tassinari, Marianna, Mottolese, Nicola, Galvani, Giuseppe, Ferrara, Domenico, Gennaccaro, Laura, Loi, Manuela, Medici, Giorgio, Candini, Giulia, Rimondini, Roberto, Ciani, Elisabetta, Trazzi, Stefania
Format: Article
Language:English
Subjects:
Animal cognition
Apoptosis
Autism
Behavior
CDKL5 deficiency disorder
Dendritic branching
Dendritic spines
Down syndrome
Drug therapy
Epilepsy
Flavonoids
Health services
Hippocampus
Inflammation
Intellectual disabilities
luteolin
Maturation
Memory
Microglia
Mutation
Neurodevelopmental disorders
Neurogenesis
neuronal plasticity
Neurons
Neuroprotection
Neurotoxicity
Rodents
Schizophrenia
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:CDKL5 deficiency disorder (CDD), a rare and severe neurodevelopmental disease caused by mutations in the X-linked CDKL5 gene, is characterized by early-onset epilepsy, intellectual disability, and autistic features. Although pharmacotherapy has shown promise in the CDD mouse model, safe and effective clinical treatments are still far off. Recently, we found increased microglial activation in the brain of a mouse model of CDD, the Cdkl5 KO mouse, suggesting that a neuroinflammatory state, known to be involved in brain maturation and neuronal dysfunctions, may contribute to the pathophysiology of CDD. The present study aims to evaluate the possible beneficial effect of treatment with luteolin, a natural flavonoid known to have anti-inflammatory and neuroprotective activities, on brain development and behavior in a heterozygous Cdkl5 (+/−) female mouse, the mouse model of CDD that best resembles the genetic clinical condition. We found that inhibition of neuroinflammation by chronic luteolin treatment ameliorates motor stereotypies, hyperactive profile and memory ability in Cdkl5 +/− mice. Luteolin treatment also increases hippocampal neurogenesis and improves dendritic spine maturation and dendritic arborization of hippocampal and cortical neurons. These findings show that microglia overactivation exerts a harmful action in the Cdkl5 +/− brain, suggesting that treatments aimed at counteracting the neuroinflammatory process should be considered as a promising adjuvant therapy for CDD.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms23158719