Increased DNA methylation in the parvalbumin gene promoter is associated with methamphetamine dependence
PHARMACOGENOMICS
Authors: Veerasakul, Siriluk; Watiktinkorn, Paritat; Thanoi, Samur; Dalton, Caroline F.; Fachim, Helene A.; Nudmamud-Thanoi, Sutisa; Reynolds, Gavin P.
Abstract
Aim: The parvalbumin (PV)-containing subgroup of GABAergic neurons is particularly affected in schizophrenia and animal models of psychosis, including after methamphetamine (METH) administration. We investigated whether METH dependence and METH-induced psychosis may involve an effect on DNA methylation of the PVALB promoter. Materials & methods: The methylation of a PVALB promoter sequence was determined in 100 METH-dependent and 102 control subjects using pyrosequencing. Results: A significant increase in PVALB methylation was observed in METH dependence and METH-induced psychosis. No significant effect on long interspersed nucleotide element-1 methylation, a measure of global DNA methylation, was observed. Conclusion: These results demonstrate a specific association between elevated PVALB methylation and METH-induced psychosis. This finding may contribute to the GABAergic deficits associated with METH dependence.
Cortical fast-spiking parvalbumin interneurons enwrapped in the perineuronal net express the metallopeptidases Adamts8, Adamts15 and Neprilysin
MOLECULAR PSYCHIATRY
Authors: Rossier, J.; Bernard, A.; Cabungcal, J-H; Perrenoud, Q.; Savoye, A.; Gallopin, T.; Hawrylycz, M.; Cuenod, M.; Do, K.; Urban, A.; Lein, Ed S.
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 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 beta-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.
COA
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