Lipid mapping of the rat brain for models of disease

Abstract

Lipids not only constitute the primary component of cellular membranes and contribute to metabolism but also serve as intracellular signaling molecules and bind to specific membrane receptors to control cell proliferation, growth and convey neuroprotection. Over the last several decades, the development of new analytical techniques, such as imaging mass spectrometry (IMS), has contributed to our understanding of their involvement in physiological and pathological conditions. IMS allows researchers to obtain a wide range of information about the spatial distribution and abundance of the different lipid molecules that is crucial to understand brain functions. The primary aim of this study was to map the spatial distribution of different lipid species in the rat central nervous system (CNS) using IMS to find a possible relationship between anatomical localization and physiology. The data obtained were subsequently applied to a model of neurological disease, the 192IgG-saporin lesion model of memory impairment. The results were obtained using a LTQ-Orbitrap XL mass spectrometer in positive and negative ionization modes and analyzed by ImageQuest and MSIReader software. A total of 176 different molecules were recorded based on the specific localization of their intensities. However, only 34 lipid species in negative mode and 51 in positive were assigned to known molecules with an error of 5ppm. These molecules were grouped by different lipid families, resulting in: Phosphatidylcholines (PC): PC (34: 1)+K⁺ and PC (32: 0)+K⁺ distributed primarily in gray matter, and PC (36: 1)+K⁺ and PC (38: 1)+Na⁺ distributed in white matter. Phosphatidic acid (PA): PA (38: 3)+K⁺ in white matter, and PA (38: 5)+K⁺ in gray matter and brain ventricles. Phosphoinositol (PI): PI (18: 0/20: 4)-H⁺ in gray matter, and PI (O-30: 1) or PI (P-30: 0)-H⁺ in white matter. Phosphatidylserines (PS): PS (34: 1)-H⁺ in gray matter, and PS (38: 1)-H⁺ in white matter. Sphingomyelin (SM) SM (d18: 1/16: 0)-H⁺ in ventricles and SM (d18: 1/18: 0)-H⁺ in gray matter. Sulfatides (ST): ST (d18: 1/24: 1)-H⁺ in white matter. The specific distribution of different lipids supports their involvement not only in structural and metabolic functions but also as intracellular effectors or specific receptor ligands and/or precursors. Moreover, the specific localization in the CNS described here will enable us to analyze lipid distribution to identify their physiological conditions in rat models of neurodegenerative pathologies, such as Alzheimer's disease. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá.

Keywords: Alzheimer's disease; Brain; Imaging mass spectrometry; Phospholipid; Rat; cholinergic lesion.