Decreased 16:0/20:4-phosphatidylinositol level in the post-mortem prefrontal cortex of elderly patients with schizophrenia

Junya Matsumoto,Yuki Sugiura,Yasuto Kunii,Noritaka Masaki,Yoshio Hashizume,Takeshi Kondo,Michihiko Waki,Takahiro Hayasaka,Hirooki Yabe,Sakon Yamamoto,Mitsutoshi Setou,Shinji Sato,Akira Wada,Takehiko Sasaki,Mizuki Hino,Shin-Ichi Niwa,Dai Yuki,Hiroki Nakanishi,Hiroyasu Akatsu

doi:10.1038/srep45050

Abstract

The etiology of schizophrenia includes phospholipid abnormalities. Phospholipids are bioactive substances essential for brain function. To analyze differences in the quantity and types of phospholipids present in the brain tissue of patients with schizophrenia, we performed a global analysis of phospholipids in multiple brain samples using liquid chromatography electrospray ionization mass/mass spectrometry (LC-ESI/MS/MS) and imaging mass spectrometry (IMS). We found significantly decreased 16:0/20:4-phosphatidylinositol (PI) levels in the prefrontal cortex (PFC) in the brains from patients with schizophrenia in the LC-ESI/MS/MS, and that the 16:0/20:4-PI in grey matter was most prominently diminished according to the IMS experiments. Previous reports investigating PI pathology of schizophrenia did not identify differences in the sn-1 and sn-2 fatty acyl chains. This study is the first to clear the fatty acid composition of PI in brains from patients with schizophrenia. Alteration in the characteristic fatty acid composition of PI may also affect neuronal function, and could play a role in the etiology of schizophrenia. Although further studies are necessary to understand the role of reduced 16:0/20:4-PI levels within the prefrontal cortex in the etiology of schizophrenia, our results provide insight into the development of a novel therapy for the clinical treatment of schizophrenia.

Highlights

16:0/20:4-PI levels within the prefrontal cortex in the etiology of schizophrenia, our results provide insight into the development of a novel therapy for the clinical treatment of schizophrenia
Dysfunction of the prefrontal cortex (PFC) in schizophrenia is associated with the cognitive impairment that is central to schizophrenia[17]
Some studies indicate that Brodmann area 10 (BA10) in the PFC is involved in multitasking, social cognition, working memory, and episodic memory[18,19]; we focused on the PFC and extracted lipids from BA10 of post-mortem brains

Summary

Introduction

16:0/20:4-PI levels within the prefrontal cortex in the etiology of schizophrenia, our results provide insight into the development of a novel therapy for the clinical treatment of schizophrenia. Phospholipids are bioactive substances essential for brain function, and previous works indicated a link between them and the etiology of schizophrenia[1,5]. These studies indicated alterations of the phospholipids[1,5], but methodological constraints prevented their reporting on the details of the affected phospholipids, such as the specific fatty acid compositions/combinations. While magnetic resonance spectroscopy can be applied to the study of living patients’ brains[16], it cannot distinguish the different specific types of fatty acid residues, so the above-mentioned phospholipid analyses require the use of post-mortem tissue. The combination of microscopy with high-resolution matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS) promises to be a useful tool in post-mortem brain studies of schizophrenia[22], given its capacity for unprecedented detail and ability to create a precise profile of the phospholipids in post-mortem brains

Methods

Results

Conclusion