Molecular Psychiatry · 2014 · 102 citations · 26 references
Life SciencesNeurobiologyNeuroscienceCellular NeuroscienceMolecular NeurobiologyMolecular NeuroscienceAmyloid FormationNeurotransmissionProteolytic EnzymesProteolytic ProcessingAmyloid Beta PeptidesCalcium-binding Protein ExpressionExtracellular ProteasesNeuropeptide ProcessingPatch Clamp TechniquesPerineuronal Net RemodelingProtease FamiliesSomatosensory Cortex Physiology
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 four 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 (MPs) was analyzed by single-cell reverse transcriptase 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 five clusters, two fast-spiking interneuron 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, whereas the ones expressing Sst, PV-Sst, were not.
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