Prenatal treatment with preimplantation factor improves early postnatal neurogenesis and cognitive impairments in a mouse model of Down syndrome.
Animals
Down Syndrome
/ drug therapy
Neurogenesis
/ drug effects
Disease Models, Animal
Mice
Female
Pregnancy
Hippocampus
/ metabolism
Microglia
/ metabolism
Protein Serine-Threonine Kinases
/ metabolism
Protein-Tyrosine Kinases
/ metabolism
Dyrk Kinases
Cognitive Dysfunction
/ drug therapy
Male
Cognition Disorders
/ drug therapy
Cyclin D1
Dp(16)1Yey mice
S100 beta
Social behavior
Vocalizations
c-myc
Journal
Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402
Informations de publication
Date de publication:
13 May 2024
13 May 2024
Historique:
received:
19
01
2024
accepted:
18
04
2024
revised:
01
04
2024
medline:
13
5
2024
pubmed:
13
5
2024
entrez:
13
5
2024
Statut:
epublish
Résumé
Down syndrome (DS) is a genetic disease characterized by a supernumerary chromosome 21. Intellectual deficiency (ID) is one of the most prominent features of DS. Central nervous system defects lead to learning disabilities, motor and language delays, and memory impairments. At present, a prenatal treatment for the ID in DS is lacking. Subcutaneous administration of synthetic preimplantation factor (sPIF, a peptide with a range of biological functions) in a model of severe brain damage has shown neuroprotective and anti-inflammatory properties by directly targeting neurons and microglia. Here, we evaluated the effect of PIF administration during gestation and until weaning on Dp(16)1Yey mice (a mouse model of DS). Possible effects at the juvenile stage were assessed using behavioral tests and molecular and histological analyses of the brain. To test the influence of perinatal sPIF treatment at the adult stage, hippocampus-dependent memory was evaluated on postnatal day 90. Dp(16)1Yey pups showed significant behavioral impairment, with impaired neurogenesis, microglial cell activation and a low microglial cell count, and the deregulated expression of genes linked to neuroinflammation and cell cycle regulation. Treatment with sPIF restored early postnatal hippocampal neurogenesis, with beneficial effects on astrocytes, microglia, inflammation, and cell cycle markers. Moreover, treatment with sPIF restored the level of DYRK1A, a protein that is involved in cognitive impairments in DS. In line with the beneficial effects on neurogenesis, perinatal treatment with sPIF was associated with an improvement in working memory in adult Dp(16)1Yey mice. Perinatal treatment with sPIF might be an option for mitigating cognitive impairments in people with DS.
Identifiants
pubmed: 38739166
doi: 10.1007/s00018-024-05245-9
pii: 10.1007/s00018-024-05245-9
doi:
Substances chimiques
Protein Serine-Threonine Kinases
EC 2.7.11.1
Protein-Tyrosine Kinases
EC 2.7.10.1
Dyrk Kinases
EC 2.7.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
215Informations de copyright
© 2024. The Author(s).
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