Phosphatidylethanolamine deficiency and triglyceride overload in perilesional cortex contribute to non-goal-directed hyperactivity after traumaticm brain injury in ice
- Traumatic brain injury (TBI) is often complicated by long-lasting disabilities, including headache, fatigue, insomnia, hyperactivity, and cognitive deficits. In a previous study in mice, we showed that persistent non-goal-directed hyperactivity is a characteristic post-TBI behavior that was associated with low levels of endocannabinoids in the perilesional cortex. We now analyzed lipidome patterns in the brain and plasma in TBI versus sham mice in association with key behavioral parameters and endocannabinoids. Lipidome profiles in the plasma and subcortical ipsilateral and contralateral brain were astonishingly equal in sham and TBI mice, but the ipsilateral perilesional cortex revealed a strong increase in neutral lipids represented by 30 species of triacylglycerols (TGs) of different chain lengths and saturation. The accumulation of TG was localized predominantly to perilesional border cells as revealed by Oil Red O staining. In addition, hexosylceramides (HexCer) and phosphatidylethanolamines (PE and ether-linked PE-O) were reduced. They are precursors of gangliosides and endocannabinoids, respectively. High TG, low HexCer, and low PE/PE-O showed a linear association with non-goal-directed nighttime hyperactivity but not with the loss of avoidance memory. The analyses suggest that TG overload and HexCer and PE deficiencies contributed to behavioral dimensions of post-TBI psychopathology.
Verfasserangaben: | Lisa Katharina HahnefeldORCiDGND, Alexandra Vogel, Robert GurkeORCiDGND, Gerd GeisslingerORCiDGND, Michael K. E. SchäferORCiD, Irmgard TegederORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-692903 |
DOI: | https://doi.org/10.3390/biomedicines10040914 |
ISSN: | 2227-9059 |
Titel des übergeordneten Werkes (Englisch): | Biomedicines |
Verlag: | MDPI |
Verlagsort: | Basel |
Dokumentart: | Wissenschaftlicher Artikel |
Sprache: | Englisch |
Datum der Veröffentlichung (online): | 15.04.2022 |
Datum der Erstveröffentlichung: | 15.04.2022 |
Veröffentlichende Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Datum der Freischaltung: | 06.05.2024 |
Freies Schlagwort / Tag: | cortical impact; hyperactivity; microglia; phosphatidylethanolamines; traumatic brain injury; triglycerides |
Jahrgang: | 10 |
Ausgabe / Heft: | 4, art. 914 |
Aufsatznummer: | 914 |
Seitenzahl: | 21 |
Erste Seite: | 1 |
Letzte Seite: | 21 |
Bemerkung: | The study was supported by the Deutsche Forschungsgemeinschaft (DFG; CRC1039 A03 to I.T.; CRC1080 C02 to I.T., CRC1039 Z01 to G.G.) and the Fraunhofer Cluster of Excellence for Immune-Mediated Diseases (G.G.). The funders had no role in the collection, analysis, and interpretation of data; writing of the manuscript; or decision to submit the article for publication. |
Institute: | Medizin |
DDC-Klassifikation: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Lizenz (Deutsch): | ![]() |