Brain phospholipid metabolism

Quantifying and Imaging Brain Phospholipid Metabolism In Vivo Using Radiolabeled Long Chain Fatty Acids... 

This critical review describes an experimental method and mathematical model to quanfily in vivo incorporation rates, half-lives, and turnover rates of FAs into brain phospholipids. FA incorporation is independent of cerebral blood flow and is thus a direct measure of brain phospholipid metabolism. Because specific FAs enter specific phospholipids at stereospecific positions, a combination of saturated and polyunsaturated FA labels can he used to investigate the active participation of phospholipids in brain signal transduction, membrane remodeling, and neuroplasticity. 

Williamson PC. Drost DJ. P Magnetic resonance spectroscopy in the assessment of brain phospholipid metabolism in schizophrenia. In Peet M, Glen I, Horrobin DF, eds. Phospholipid Spectrum Disorder in Psychiatry. Marius, Camforth, UK, 1999, pp. 45-55. 

There is. however, a need for direct measurement within the brain. This is notoriously difficult to carry out, but in 1991, Pettegrew et al. used P magnetic resonance spectroscopy (MRS) to make a direct examination of brain phospholipid metabolism. Using a... 

Pettegrew, J. W., Keshavan, M. S., Panchalingam, K. et al. Alterations in brain high-energy phosphate and membrane phospholipid metabolism in first-episode, drug-naive schizophrenics. A pilot study of the dorsal prefrontal cortex by in vivo phosphorus 31 nuclear magnetic resonance spectroscopy. Arch. Gen. Psychiat. 48 563-568,1991. 

We also see increasing use for P MRS in studying mental illnesses. The ability to characterize tissue energetics (via PCr and ATP) and phospholipid metabolism (via PMEs and PDEs) in sufficiently localized brain regions should help clarify the roles of mitochondrial dysfunction and phospholipid metabolism in schizophrenia and BD, as suggested by earlier efforts... 

Farooqui A. A. and Horrocks L. A. (1991). Excitatory amino acid receptors, neural membrane phospholipid metabolism and neurological disorders. Brain Res. Rev. 16 171-191. 

Such imbalanced antioxidant systems in schizophrenia could lead to oxidative stress- and ROS-mediated injury as supported by increased lipid peroxidation products and reduced membrane polyunsaturated fatty acids (PUFAs). Decrease in membrane phospholipids in blood cells of psychotic patients (Keshavan et al., 1993 Reddy et al., 2004) and fibroblasts from drug-naive patients (Mahadik et al., 1994) as well as in postmortem brains (Horrobin et al., 1991) have indeed been reported. It has also been suggested that peripheral membrane anomalies correlate with abnormal central phospholipid metabolism in first-episode and chronic schizophrenia patients (Pettegrewet al., 1991 Yao et al., 2002). Recently, a microarray and proteomic study on postmortem brain showed anomalies of mitochondrial function and oxidative stress pathways in schizophrenia (Prabakaran et al., 2004). Mitochondrial dysfunction in schizophrenia has also been observed by Ben-Shachar (2002) and Altar et al. (2005). As main ROS producers, mitochondria are particularly susceptible to oxidative damage. Thus, a deficit in glutathione (GSH) or immobilization stress induce greater increase in lipid peroxidation and protein oxidation in mitochondrial rather than in cytosolic fractions of cerebral cortex (Liu et al., 1996). 

Jensen JE, Miller J, Williamson PC, Neufeld RW, Menon RS, et al. 2004. Focal changes in brain energy and phospholipid metabolism in first-episode schizophrenia 31p-mrs chemical shift imaging study at 4 tesla. Br J Psychiatry 184 ... 

Purdon AD, Rapoport SL Energy requirements for two aspects of phospholipid metabolism in mammalian brain. Biochem J 1998 335 313-318. 

Jope RS, Jenden DJ. Choline and phospholipid metabolism and the synthesis of acetylchohne in rat brain. J Neurosci Res 1979 4 69-82. 

Before 1940 it was generally considered that phosphohpids, once laid down in the nervous system of mammals during growth and development, were comparatively static entities. However, later studies using (32p)oithophosphate showed that brain phospholipids as a whole are metabolically active in vivo (Ansell and Dohmen, 1957, Crokin and Sun, 1978). In the present study, by following the changes in phospholipid fatty acid composition, we have demonstrated that an n-3 fatty acid-enriched diet can rapidly reverse a severe n-3 fatty acid deficiency in the brains of primates. The phospholipid fatty acids of the cerebral cortex of juvenile monkeys are in adynamic state and are subject to continuous turnover under certain defined conditions. 

For many years, phospholipid metabolism has been ignored in psychiatric and neurological disorders. This situation is changing rapidly and this approach is poised to become part of the new mainstream in research on brain disorders. 

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