m⁶A Modification Involves in Enriched Environment-Induced Neurogenesis and Cognition Enhancement

Area of Science:

• Neuroscience
• Epigenetics
• Molecular Biology

Background:

• Previous research indicates enriched environments (EE) promote neurogenesis and modify DNA/histone.
• The impact of EE on the epitranscriptome during neuronal development is not well understood.

Purpose of the Study:

• To investigate the effect of EE on the epitranscriptome, specifically N6-Methyladenosine (m6A) modifications, in the context of postnatal neuronal development.
• To explore how EE influences neural stem/progenitor cells and cognitive functions.

Main Methods:

• Exposure of animals to an enriched environment.
• Assessment of adult neural stem/progenitor cells (aNSPCs) proliferation and neuronal differentiation.
• Cognitive function tests.
• N6-Methyladenosine (m6A) immunoprecipitation followed by deep sequencing (MeRIP-seq) to analyze global m6A levels and distribution.
• Western blot analysis to determine protein levels of m6A-related enzymes (Fto, METTL3, METTL14).

Main Results:

• EE exposure enhanced aNSPC proliferation and neuronal differentiation.
• EE improved cognitive capabilities and altered gene expression related to neuronal development and memory.
• EE increased global m6A levels and induced differential m6A mRNA modifications.
• Genes with differential m6A modification were associated with neuronal development and neurogenesis.
• EE decreased the protein level of the m6A eraser Fto, without affecting m6A writers METTL3 and METTL14.

Conclusions:

• EE exposure significantly impacts the epitranscriptome by inducing differential m6A mRNA modifications during postnatal neuronal development.
• This finding reveals a novel epigenetic mechanism through which environmental factors influence brain development and function.