Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Brain Area-Specific Methylation Signatures Mark Patients With Schizophrenia

Version 1 : Received: 12 December 2023 / Approved: 13 December 2023 / Online: 13 December 2023 (03:27:09 CET)
Version 2 : Received: 4 January 2024 / Approved: 5 January 2024 / Online: 5 January 2024 (07:17:28 CET)

How to cite: Morgera, V.; Feola, A.; Improda, T.; Cuomo, M.; Porcellini, A.; Pezone, A. Brain Area-Specific Methylation Signatures Mark Patients With Schizophrenia. Preprints 2023, 2023120923. https://doi.org/10.20944/preprints202312.0923.v1 Morgera, V.; Feola, A.; Improda, T.; Cuomo, M.; Porcellini, A.; Pezone, A. Brain Area-Specific Methylation Signatures Mark Patients With Schizophrenia. Preprints 2023, 2023120923. https://doi.org/10.20944/preprints202312.0923.v1

Abstract

D-Aspartate and D-Serine serve as primary agonists at glutamate receptors, playing a crucial role in modulating synaptic plasticity and cell migration within the central nervous system. The pre-cise regulation of their levels is essential and intricately linked to the expression of their synthetic and catabolic enzymes, which are, in turn, primarily influenced by epigenetic modifications. In a comprehensive analysis, we examined the methylation profiles of the promoters and transcription start sites of critical genes associated with D-Aspartate and D-Serine metabolism in human post-mortem brain tissues sourced from normal individuals and those diagnosed with schizo-phrenia. Our approach involved a qualitative method capable of identifying specific families of methylated alleles known as epialleles, sharing a common pattern of methylated non-contiguous CpGs, referred to as cores. These methylated traits exhibit stability and consistency within com-plex populations of diverse DNA-methylated molecules. Our findings reveal brain area-specific methylation signatures to the DDO, DAO and DAOA genes serving as distinctive markers that differentiate normal brain areas from those affected by schizophrenia. These methylation patterns align with the reported high D-Aspartate and low D-Serine levels observed in schizophrenic brain areas. The study suggests a potential link between epigenetic modifications and the dysreg-ulation of these neurotransmitters in schizophrenia.

Keywords

DNA methylation in healthy and disease; methyl-CpG's configurations; schizophrenia

Subject

Biology and Life Sciences, Cell and Developmental Biology

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