Targeted lipidomics profile and NMR metabolomics of injured mouse brain (Comunicazione a convegno)

Type
Label
  • Targeted lipidomics profile and NMR metabolomics of injured mouse brain (Comunicazione a convegno) (literal)
Anno
  • 2014-01-01T00:00:00+01:00 (literal)
Alternative label
  • F.Piscitelli 1, D. Paris1, D. Melck1, C. Giordano2, L. Luongo2, S. Maione2, A. Motta1, V. Di Marzo1 (2014)
    Targeted lipidomics profile and NMR metabolomics of injured mouse brain
    in "The Metabolomics Approaches: Advanced Analytical Tools (Challenges, perspectives and applications)", Padova, 10-11/11/2014
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • F.Piscitelli 1, D. Paris1, D. Melck1, C. Giordano2, L. Luongo2, S. Maione2, A. Motta1, V. Di Marzo1 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • 1. Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Via Campi Flegrei 34, Pozzuoli (NA), Italy; 2. Department of Experimental Medicine/Division of Pharmacology, Second University of Naples, via Costantinopoli, 16 80138, Naples, Italy. (literal)
Titolo
  • Targeted lipidomics profile and NMR metabolomics of injured mouse brain (literal)
Abstract
  • Traumatic brain injury (TBI) is the leading cause of death in the young age group and the most commonly identified cause of epilepsy in adult populations older than 35 years. At present, there are no effective drugs to treat brain injury [1]. The role of the endocannabinoid system in neuroprotection is well established. Several groups reported enhanced levels of the endocannabinoid anandamide (AEA) after acute injury, and in response to TBI there is local and transient accumulation of the other endogenous agonist of cannabinoid receptors, 2-arachidonoylglycerol (2-AG) at the site of injury, peaking at 4 h and sustained up to at least 24 h [2]. Furthermore, very recently, Naqvi and co-workers [3] found that cigarette smokers presenting with TBI, with damage at the level of the insula, experience a cessation of smoking. Given the reinforcing role of endocannabinoids and CB1 receptors in nicotine self-administration, it is possible that TBI is accompanied by reduced endocannabinoid levels in the insula. The aim of this study was, therefore, to investigate further the alterations of endocannabinoid levels in a model of mouse TBI and to discover new endocannabinoid molecules possibly involved in this process through the use of very sensitive and specific \"targeted lipidomics\" methods involving high resolution LC-ESI-IT-ToF (Liquid Chromatography-ElectroSpray Ionization-Ion Trap-Time of Flight) and NMR based metabolomics. Mice underwent TBI using the weight drop model and were divided into three experimental groups: naïve (untreated brains), control (only surgically incised brains) and TBI (injured brains). Animals were decapitated one day after injury and brains were divided into two halfs. Hippocampus and insular cortex were dissected from one half for lipidomics analysis and the other half was used for NMR analysis. Interestingly, this mild model of TBI led to a reduction of AEA levels and no changes in 2-AG. NMR based metabolic profiling was performed on both hydrophilic and lipophilic brain tissue extracts in order to investigate possible neurochemical alterations induced in mice after brain injury. NMR samples were discriminated using Projection to Latent Structure Discriminant Analysis (PLS-DA). Control and TBI groups showed low levels of L-Glutamine and L-Glutamic acid with respect to the naïve group, thus suggesting impairment in the glutamine-glutamate cycle. Individually, the control group exhibited high levels of neurotransmitters Taurine and GABA, together with N-Acetyl-L Aspartic acid and Creatine/Phosphocreatine, which are involved in lipid synthesis and energy metabolism. On the other hand, the TBI group presented high concentrations of short chain lipids and myo-Inositol, which probably act as neuro-protecting compounds in response to brain injury. In conclusion, we coupled targeted lipidomics with NMR metabolomics as a joint strategy to achieve a more complete characterization of brain damage and, possibly, identify putative markers associated with the alteration induced by traumatic brain injury. Apart from the LC-MS results, which suggest that the reduced levels of endocannabinoids following TBI might be one of the underlying causes of decreased nicotine self-administration, we found significant changes in the levels of metabolites involved in multiple neuronal activities, including neurotransmitter activity, neuronal osmoregulation and signaling. (literal)
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