Local co-expression of GLP1R and INS in human cortical interneurons

Area of Science:

• Neuroscience
• Molecular Biology
• Metabolic Regulation

Background:

• Glucagon-like peptide-1 receptor (GLP1R) and insulin (INS) are key in peripheral metabolism.
• Emerging evidence indicates central nervous system roles for GLP1R and INS.
• Understanding their intracortical functions is crucial for brain health.

Purpose of the Study:

• To investigate the expression of GLP1R and INS in specific human cortical interneuron subtypes.
• To explore the potential for local intracortical metabolic signaling pathways.

Main Methods:

• Laser capture microdissection of human cortical layer 1 GABAergic interneurons.
• Transcriptomic subtyping using digital PCR for LAMP5, SV2C, and PRSS12 markers.
• Quantification of GLP1R and INS mRNA using single-cell digital PCR and spatial validation with RNAscope Hi-Plex in situ hybridization.

Main Results:

• Neurogliaform and rosehip cells showed significantly higher GLP1R and INS expression compared to other LAMP5 interneurons.
• GLP1R mRNA was detected in 44/72 neurogliaform and 18/36 rosehip cells.
• INS mRNA was detected in 29/72 neurogliaform and 11/36 rosehip cells, with non-random co-expression.

Conclusions:

• Human cortical neurogliaform and rosehip interneurons selectively co-express GLP1R and INS.
• This co-expression supports the existence of a local intracortical GLP1R-insulin signaling loop.
• Findings offer insights into cerebral glucose regulation and neurodegenerative diseases like mild cognitive impairment in diabetes mellitus.