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Updated: Jun 1, 2025

A Chromatin Assay for Human Brain Tissue
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A method for HDAC activity screening in postmortem human brain. A proof-of-concept study with antipsychotics.

Oihane Martínez-Peula1, Alfredo Ramos-Miguel2, Carolina Muguruza2

  • 1Department of Pharmacology, University of the Basque Country, UPV/EHU, Leioa, Spain.

Journal of Neuroscience Methods
|January 20, 2025
PubMed
Summary
This summary is machine-generated.

We developed a new assay to measure histone deacetylase (HDAC) activity in postmortem brain samples. This method confirmed that antipsychotic drugs do not alter class I HDAC activity in schizophrenia patients.

Keywords:
AntipsychoticsEnzymatic assayEpigeneticsHDACHuman postmortem brain

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Area of Science:

  • Neuroscience
  • Biochemistry
  • Pharmacology

Background:

  • Histone deacetylase (HDAC) activity is dysregulated in various brain disorders.
  • Antipsychotic drugs (APs) are used to treat schizophrenia, but their impact on brain HDAC activity is unclear.

Purpose of the Study:

  • To optimize and characterize a reliable assay for measuring HDAC activity in postmortem human brain samples.
  • To investigate the effect of APs on HDAC activity in the brains of schizophrenia subjects.

Main Methods:

  • Developed and validated a cost-efficient HDAC activity assay using Boc-Lys(Ac)-AMC substrate.
  • Characterized assay parameters including subcellular fraction and protein concentration.
  • Utilized the assay for enzyme kinetics and screening of HDAC inhibitors (HDACis).
  • Assessed the effect of APs on class I HDAC activity in postmortem human brain and rat models.

Main Results:

  • The optimized assay demonstrated reliability and detected class I HDAC activity, with IC50 values consistent with prior research.
  • Inhibition studies confirmed the assay's ability to identify class I HDAC activity.
  • No modulation of class I HDAC activity was observed in postmortem human brain samples treated with APs.
  • Enzyme kinetic studies in rats treated with APs also showed no effect on class I HDAC activity.

Conclusions:

  • An optimized and validated assay for measuring HDAC activity in postmortem human brain samples was successfully developed.
  • Antipsychotic drugs were found to have no modulatory effect on class I HDAC activity in the studied samples.