# Characterization of the Lipidome of Neurons in Mouse Brain Nuclei Using Imaging Mass Spectrometry

**Authors:** Cristina Huergo, Laura de las Heras-García, Jone Razquin, Yuri Rueda, Cristina Miguélez, José A. Fernández

PMC · DOI: 10.1021/acs.analchem.5c08016 · Analytical Chemistry · 2026-01-13

## TL;DR

This study uses imaging mass spectrometry to identify unique lipid profiles in specific mouse brain neurons, revealing sex-based differences in some regions.

## Contribution

The study introduces a method to characterize neuronal lipidomes with sex-based comparisons in specific brain nuclei.

## Key findings

- Each neuronal population has a distinct lipid profile across all analyzed lipid classes.
- Sex-based differences were observed in phosphatidylcholine/phosphatidylethanolamine-ether, phosphatidylinositol, and sphingomyelin in LC neurons.
- Mesencephalic neurons showed more pronounced lipidomic differences compared to SNc neurons.

## Abstract

Understanding the
molecular composition of the brain at cellular
level is essential for deciphering the metabolic alterations associated
with brain diseases. Furthermore, the different prevalence of some
neurological diseases between males and females highlight the importance
of incorporating gender factor in such studies. Here, we demonstrate
that using imaging mass spectrometry in negative polarity it is possible
to isolate and characterize the lipidome of specific neuronal populations
in the mouse brain, including the locus coeruleus (LC), mesencephalic
neurons and the substantia nigra pars compacta (SNc). Neuronal identity
was validated through immunofluorescence on adjacent serial sections.
Comparative analysis revealed that each neuronal population presents
a distinct and well-defined lipidic profile, with differences extending
across all lipid classes analyzed. Regarding sex-based differences,
we found discrete differences in phosphatidylcholine/phosphatidylethanolamine-ether,
phosphatidylinositol and sphingomyelin LC neurons. Lipidomic differences
were more pronounced in mesencephalic neurons, whereas no significant
sex-dependant differences were observed in SNc lipid composition.
These findings lay the groundwork for future studies aimed at identifying
lipid metabolic dysregulations in the context of neurodegenerative
diseases.

## Linked entities

- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, Podxl (podocalyxin-like) [NCBI Gene 192181] {aka PC, PCLP-1, podocalyxin}, Nefl (neurofilament light chain) [NCBI Gene 83613] {aka NF-L, NF68, Nfl}, Avil (advillin) [NCBI Gene 11567] {aka Advil, DOC6}, ABCA7 (ATP binding cassette subfamily A member 7) [NCBI Gene 10347] {aka ABCA-SSN, ABCX, AD9}, Th (tyrosine hydroxylase) [NCBI Gene 21823], Pvalb (parvalbumin) [NCBI Gene 19293] {aka PV, Parv, Pva}
- **Diseases:** Alzheimer's disease (MESH:D000544), neurological disorders (MESH:D009461), brain diseases (MESH:D001927), inflammatory (MESH:D007249), CNS disorders (MESH:D002493), PD (MESH:D010300), neurodegeneration (MESH:D019636), SNc degeneration (MESH:D015868), neuroinflammation (MESH:D000090862), neurological diseases (MESH:D020271)
- **Chemicals:** Triton X-100 (MESH:D017830), DHA (MESH:D004281), Paraformaldehyde (MESH:C003043), cardiolipins (MESH:D002308), Acetone (MESH:D000096), Hoechst 33342 (MESH:C017807), PUFA (MESH:D005231), oxygen (MESH:D010100), PS (MESH:D010718), PC (MESH:D010713), 1,5-diaminonaphthalene (MESH:C510889), PBS (MESH:D007854), phospholipids (MESH:D010743), glycerophospholipid (MESH:D020404), cholesterol (MESH:D002784), noradrenaline (MESH:D009638), water (MESH:D014867), isoflurane (MESH:D007530), ammonium acetate (MESH:C018824), NaCl (MESH:D012965), Lipids (MESH:D008055), fatty acid (MESH:D005227), Alexa Fluor 488 (MESH:C000711379), calcium (MESH:D002118), AA (MESH:D016718), myo-inositol (MESH:D007294), Methanol (MESH:D000432), prostaglandins (MESH:D011453), PE (MESH:C483858), Plasmalogens (MESH:D010955), PI (MESH:D010716), Ca2+ (-), IPA (MESH:D019840), PG (MESH:D010715), SM (MESH:D013109), acetonitrile (MESH:C032159), Sphingolipids (MESH:D013107), silica (MESH:D012822), Isopentane (MESH:C067038), lysophosphatidic acid (MESH:C032881), B (MESH:D001895), neuromelanin (MESH:C014121)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Gallus gallus (bantam, species) [taxon 9031]
- **Mutations:** A53T, L444P
- **Cell lines:** HT22 — Mus musculus (Mouse), Transformed cell line (CVCL_0321), SNCA-A53T — Homo sapiens (Human), Parkinson disease 1, autosomal dominant, Induced pluripotent stem cell (CVCL_A8LY)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12856826/full.md

## References

79 references — full list in the complete paper: https://tomesphere.com/paper/PMC12856826/full.md

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Source: https://tomesphere.com/paper/PMC12856826