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Dysregulated miR-124 mediates impaired social memory behavior caused by paternal early social isolation.
- Source :
-
Translational psychiatry [Transl Psychiatry] 2024 Sep 28; Vol. 14 (1), pp. 392. Date of Electronic Publication: 2024 Sep 28. - Publication Year :
- 2024
-
Abstract
- Early social isolation (SI) leads to various abnormalities in emotion and behavior during adulthood. However, the negative impact of SI on offspring remains unclear. This study has discovered that paternal early SI causes social memory deficits and anxiety-like behavior in F1 young adult mice, with alterations of myelin and synapses in the medial prefrontal cortex (mPFC). The 2-week SI in the F1 progeny exacerbates social memory impairment and hypomyelination in the mPFC. Furthermore, the down-regulation of miR-124, a key inhibitor of myelinogenesis, or over-expression of its target gene Nr4a1 in the mPFC of the F1 mice improves social interaction ability and enhances oligodendrocyte maturation and myelin formation. Mechanistically, elevated levels of miR-124 in the sperm of paternal SI mice are transmitted epigenetically to offspring, altering the expression levels of miR-124/Nr4a1/glucocorticoid receptors in mPFC oligodendrocytes. This, in turn, impedes the establishment of myelinogenesis-dependent social behavior. This study unveils a novel mechanism through which miR-124 mediates the intergenerational effects of early isolation stress, ultimately impairing the establishment of social behavior and neurodevelopment.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Mice
Male
Oligodendroglia metabolism
Mice, Inbred C57BL
Memory Disorders genetics
Memory Disorders metabolism
Behavior, Animal physiology
Myelin Sheath metabolism
Myelin Sheath genetics
Anxiety genetics
Anxiety metabolism
Female
MicroRNAs genetics
MicroRNAs metabolism
Social Isolation
Prefrontal Cortex metabolism
Social Behavior
Subjects
Details
- Language :
- English
- ISSN :
- 2158-3188
- Volume :
- 14
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Translational psychiatry
- Publication Type :
- Academic Journal
- Accession number :
- 39341799
- Full Text :
- https://doi.org/10.1038/s41398-024-03109-1