Membrane-lipid homeostasis in a prodromal rat model of Alzheimer's disease: Characteristic profiles in ganglioside distributions during aging detected using MALDI imaging mass spectrometry

Sarah Caughlin; Shikhar Maheshwari; Yuksel Agca; Cansu Agca; Aaron J Harris; Kristina Jurcic; Ken K-C Yeung; David F Cechetto; Shawn N Whitehead

doi:10.1016/j.bbagen.2018.03.011

Membrane-lipid homeostasis in a prodromal rat model of Alzheimer's disease: Characteristic profiles in ganglioside distributions during aging detected using MALDI imaging mass spectrometry

Biochim Biophys Acta Gen Subj. 2018 Jun;1862(6):1327-1338. doi: 10.1016/j.bbagen.2018.03.011. Epub 2018 Mar 13.

Authors

Sarah Caughlin¹, Shikhar Maheshwari¹, Yuksel Agca², Cansu Agca², Aaron J Harris³, Kristina Jurcic³, Ken K-C Yeung³, David F Cechetto¹, Shawn N Whitehead⁴

Affiliations

¹ Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
² Department of Veterinary Pathobiology, University of Missouri College of Veterinary Medicine, Columbia, MO, USA.
³ Department of Chemistry, Department of Biochemistry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
⁴ Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada. Electronic address: shawn.whitehead@schulich.uwo.ca.

PMID: 29545134
DOI: 10.1016/j.bbagen.2018.03.011

Abstract

Background: Accumulation of simple gangliosides GM2 and GM3, and gangliosides with longer long-chain bases (d20:1) have been linked to toxicity and the pathogenesis of Alzheimer's disease (AD). Conversely, complex gangliosides, such as GM1, have been shown to be neuroprotective. Recent evidence using matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS) has demonstrated that a-series gangliosides are differentially altered during normal aging, yet it remains unclear how simple species are shifting relative to complex gangliosides in the prodromal stages of AD.

Methods: Ganglioside profiles in wild-type (Wt) and transgenic APP21 Fischer rats were detected and quantified using MALDI-IMS at P0 (birth), 3, 12, and 20 months of age and each species quantified to allow for individual species comparisons.

Results: Tg APP21 rats were found to have a decreased level of complex gangliosides in a number of brain regions as compared to Wt rats and showed higher levels of simple gangliosides. A unique pattern of expression was observed in the white matter as compared to gray matter regions, with an age-dependent decrease in GD1 d18:1 species observed and significantly elevated levels of GM3 in Tg APP21 rats.

Conclusions: These results are indicative of a pathological shift in ganglioside homeostasis during aging that is exacerbated in Tg APP21 rats.

General significance: Ganglioside dysregulation may occur in the prodromal stages of neurodegenerative diseases like AD.

Keywords: Aging brain; Gangliosides; MALDI imaging mass spectrometry; Transgenic rat model.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aging*
Alzheimer Disease / metabolism*
Alzheimer Disease / pathology
Animals
Disease Models, Animal*
Gangliosides / metabolism*
Homeostasis*
Humans
Membrane Lipids / metabolism*
Rats
Rats, Inbred F344
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods*

Substances

Gangliosides
Membrane Lipids