Abstract
The in situ hybridization Allen Mouse Brain Atlas was mined for proteases expressed in the somatosensory cerebral cortex. Among the 480 genes coding for protease/peptidases, only 4 were found enriched in cortical interneurons: Reln coding for reelin; Adamts8 and Adamts15 belonging to the class of metzincin proteases involved in reshaping the perineuronal net (PNN) and Mme encoding for Neprilysin, the enzyme degrading amyloid β−peptides. The pattern of expression of metalloproteases (MP) was analyzed by single cell RT multiplex PCR after patch-clamp and was compared with the expression of 10 canonical interneurons markers and 12 additional genes from the Allen Atlas.
Clustering of these genes by K-means algorithm displays five distinct clusters. Among these 5 clusters, two fast spiking (FS) interneurons clusters expressing the calcium-binding protein Pvalb were identified, one co-expressing Pvalb with Sst (PV-Sst) and another co-expressing Pvalb with three metallopeptidases Adamts8, Adamts15 and Mme (PV-MP). By using Wisteria Floribunda agglutinin, a specific marker for PNN, PV-MP interneurons were found surrounded by PNN while the one expressing Sst, PV-Sst were not. Recent studies on animal models of schizophrenia indicated that FS-PV interneurons surrounded by PNN are protected against oxidative stress.
The present study may indicate that FS-PV interneurons expressing Sst are not protected by PNN and represent a distinct class of FS-PV highly susceptible to oxidative stress.