Solitary and Synergistic Effects of Different Hydrophilic and Hydrophobic Phospholipid Moieties on Rat Behaviors

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2024 Jun 27

PMID 38931883

Authors

Shuhei Kikuchi

Yugo Iwasaki

Mina Yoshioka

Kodai Hino

Shin-Ya Morita

Ryu Tada

Yasuhiro Uchimura

Yoshinori Kubo

Tomoya Kobayashi

Yusuke Kinoshita

Masahiro Hayashi

Yoshio Furusho

Hitoshi Tamiaki

Hiroaki Ishiyama

Minoru Kuroda

Jun Udagawa

Affiliations

Soon will be listed here.

Abstract

Glycerophospholipids have hydrophobic and hydrophilic moieties. Previous studies suggest that phospholipids with different moieties have different effects on rodent behavior; however, the relationship between chemical structures and behavioral effects remains unclear. To clarify the functions of phospholipid moieties, we injected male rats with phospholipids with different moieties and conducted behavioral tests. Exploratory activity was reduced by phosphatidylethanolamine (PE)(18:0/22:6) but not PE(18:0/18:0) or PE(18:0/20:4). Conversely, exploratory activity was increased by plasmanyl PE(16:0/22:6), which harbors an alkyl-ether linkage, but not by phosphatidylcholine (PC)(16:0/22:6) or plasmanyl PC(16:0/22:6). Docosahexaenoic acid (DHA)(22:6) and an alkyl-ether linkage in PE were thus postulated to be involved in exploratory activity. Anxiety-like behavior was reduced by plasmenyl PC(18:0/20:4), which harbors a vinyl-ether linkage, but not by PC(18:0/20:4) or plasmanyl PC(18:0/20:4), suggesting the anxiolytic effects of vinyl-ether linkage. The activation of social interaction was suppressed by PE(18:0/18:0), PE(18:0/22:6), PC(16:0/22:6), plasmanyl PE(16:0/22:6), and plasmanyl PC(16:0/22:6) but not by PE(18:0/20:4), plasmenyl PE(18:0/20:4), or plasmanyl PC(18:0/22:6). DHA may suppress social interaction, whereas arachidonic acid(20:4) or a combination of alkyl-ether linkage and stearic acid(18:0) may restore social deficits. Our findings indicate the characteristic effects of different phospholipid moieties on rat behavior, and may help to elucidate patterns between chemical structures and their effects.

Citing Articles

Ethanolamine and Vinyl-Ether Moieties in Brain Phospholipids Modulate Behavior in Rats.

Nasrin M, Kikuchi S, Uchimura Y, Yoshioka M, Morita S, Kobayashi T NeuroSci. 2024; 5(4):509-522.

PMID: 39585105 PMC: 11587438. DOI: 10.3390/neurosci5040037.

References

Koivuniemi A . The biophysical properties of plasmalogens originating from their unique molecular architecture. FEBS Lett. 2017; 591(18):2700-2713. DOI: 10.1002/1873-3468.12754. View

Heydendael W, Sharma K, Iyer V, Luz S, Piel D, Beck S . Orexins/hypocretins act in the posterior paraventricular thalamic nucleus during repeated stress to regulate facilitation to novel stress. Endocrinology. 2011; 152(12):4738-52. PMC: 3230061. DOI: 10.1210/en.2011-1652. View

Andriambelo B, Stiffel M, Roke K, Plourde M . New perspectives on randomized controlled trials with omega-3 fatty acid supplements and cognition: A scoping review. Ageing Res Rev. 2023; 85:101835. DOI: 10.1016/j.arr.2022.101835. View

Vander Weele C, Siciliano C, Tye K . Dopamine tunes prefrontal outputs to orchestrate aversive processing. Brain Res. 2018; 1713:16-31. PMC: 7575248. DOI: 10.1016/j.brainres.2018.11.044. View

Ren J, Friedmann D, Xiong J, Liu C, Ferguson B, Weerakkody T . Anatomically Defined and Functionally Distinct Dorsal Raphe Serotonin Sub-systems. Cell. 2018; 175(2):472-487.e20. PMC: 6173627. DOI: 10.1016/j.cell.2018.07.043. View

Mangold H, Weber N . Biosynthesis and biotransformation of ether lipids. Lipids. 1987; 22(11):789-99. DOI: 10.1007/BF02535533. View

Hossain M, Mawatari S, Fujino T . Plasmalogens, the Vinyl Ether-Linked Glycerophospholipids, Enhance Learning and Memory by Regulating Brain-Derived Neurotrophic Factor. Front Cell Dev Biol. 2022; 10:828282. PMC: 8864319. DOI: 10.3389/fcell.2022.828282. View

Kruttner S, Falasconi A, Valbuena S, Galimberti I, Bouwmeester T, Arber S . Absence of familiarity triggers hallmarks of autism in mouse model through aberrant tail-of-striatum and prelimbic cortex signaling. Neuron. 2022; 110(9):1468-1482.e5. DOI: 10.1016/j.neuron.2022.02.001. View

Jiang S, Xiao L, Sun Y, He M, Gao C, Zhu C . The GABAB receptor agonist STX209 reverses the autism‑like behaviour in an animal model of autism induced by prenatal exposure to valproic acid. Mol Med Rep. 2022; 25(5). PMC: 8941376. DOI: 10.3892/mmr.2022.12670. View

10.

Braverman N, Moser A . Functions of plasmalogen lipids in health and disease. Biochim Biophys Acta. 2012; 1822(9):1442-52. DOI: 10.1016/j.bbadis.2012.05.008. View

11.

Hahnefeld L, Vogel A, Gurke R, Geisslinger G, Schafer M, Tegeder I . Phosphatidylethanolamine Deficiency and Triglyceride Overload in Perilesional Cortex Contribute to Non-Goal-Directed Hyperactivity after Traumatic Brain Injury in Mice. Biomedicines. 2022; 10(4). PMC: 9033131. DOI: 10.3390/biomedicines10040914. View

12.

Hino K, Kaneko S, Harasawa T, Kimura T, Takei S, Shinohara M . Change in Brain Plasmalogen Composition by Exposure to Prenatal Undernutrition Leads to Behavioral Impairment of Rats. J Neurosci. 2019; 39(39):7689-7702. PMC: 6764206. DOI: 10.1523/JNEUROSCI.2721-18.2019. View

13.

Schneider T, Turczak J, Przewlocki R . Environmental enrichment reverses behavioral alterations in rats prenatally exposed to valproic acid: issues for a therapeutic approach in autism. Neuropsychopharmacology. 2005; 31(1):36-46. DOI: 10.1038/sj.npp.1300767. View

14.

Han X, Holtzman D, McKeel Jr D . Plasmalogen deficiency in early Alzheimer's disease subjects and in animal models: molecular characterization using electrospray ionization mass spectrometry. J Neurochem. 2001; 77(4):1168-80. DOI: 10.1046/j.1471-4159.2001.00332.x. View

15.

Zhou Z, Sayer B, Hughes D, Stark R, Epand R . Studies of phospholipid hydration by high-resolution magic-angle spinning nuclear magnetic resonance. Biophys J. 1999; 76(1 Pt 1):387-99. PMC: 1302527. DOI: 10.1016/S0006-3495(99)77205-X. View

16.

Gunaydin L, Grosenick L, Finkelstein J, Kauvar I, Fenno L, Adhikari A . Natural neural projection dynamics underlying social behavior. Cell. 2014; 157(7):1535-51. PMC: 4123133. DOI: 10.1016/j.cell.2014.05.017. View

17.

Fallatah W, Smith T, Cui W, Jayasinghe D, Di Pietro E, Ritchie S . Oral administration of a synthetic vinyl-ether plasmalogen normalizes open field activity in a mouse model of rhizomelic chondrodysplasia punctata. Dis Model Mech. 2019; 13(1). PMC: 6994958. DOI: 10.1242/dmm.042499. View

18.

Leithead A, Godino A, Barbier M, Harony-Nicolas H . Social Interaction Elicits Activity in Glutamatergic Neurons in the Posterior Intralaminar Complex of the Thalamus. Biol Psychiatry. 2023; 95(2):112-122. PMC: 10676449. DOI: 10.1016/j.biopsych.2023.05.016. View

19.

Brydges C, Bhattacharyya S, Mahmoudian Dehkordi S, Milaneschi Y, Penninx B, Jansen R . Metabolomic and inflammatory signatures of symptom dimensions in major depression. Brain Behav Immun. 2022; 102:42-52. PMC: 9241382. DOI: 10.1016/j.bbi.2022.02.003. View

20.

Morita S, Deharu Y, Takata E, Nakano M, Handa T . Cytotoxicity of lipid-free apolipoprotein B. Biochim Biophys Acta. 2008; 1778(11):2594-603. DOI: 10.1016/j.bbamem.2008.08.012. View