Hippocampus undergoes transcriptomic changes and synaptic alterations in a Slc17a5 heterozygous mouse model with...

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Sialin, encoded by Slc17a5, is crucial for lysosomal function.
• Complete loss of Sialin causes severe neurological impairment due to sialic acid storage diseases.
• The impact of partial Slc17a5 deficiency (haploinsufficiency) on adult brain function is not well understood.

Purpose of the Study:

• To investigate the effects of heterozygous Slc17a5 deletion on adult mouse brain function.
• To identify molecular mechanisms underlying cognitive deficits in Slc17a5 haploinsufficiency.

Main Methods:

• Utilized heterozygous Slc17a5 knockout mice (Slc17a5+/-).
• Assessed cognitive function using the Y-maze test.
• Performed hippocampal transcriptomic profiling and protein-protein interaction network analysis.
• Quantified synaptic protein levels (Synaptophysin).

Main Results:

• Slc17a5+/- mice displayed specific working memory deficits.
• Transcriptomic analysis revealed dysregulation in extracellular matrix organization and microtubule-based processes.
• Identified key hub genes in affected molecular pathways.
• Confirmed a significant reduction in the presynaptic protein Synaptophysin, suggesting synaptic damage.

Conclusions:

• SLC17A5 haploinsufficiency is sufficient to induce selective cognitive impairment in adult mice.
• Molecular disruptions include extracellular matrix remodeling, intracellular transport deficits, and synaptic damage.
• Provides mechanistic insights into Slc17a5's role in brain function and neurological disorders.