Hostname: page-component-848d4c4894-wzw2p Total loading time: 0 Render date: 2024-05-10T04:33:23.344Z Has data issue: false hasContentIssue false

Molecular neurodevelopment: An in vivo31P-1H MRSI study

Published online by Cambridge University Press:  01 September 2009

GERALD GOLDSTEIN
Affiliation:
VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania
KANAGASABAI PANCHALINGAM
Affiliation:
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
RICHARD J. MCCLURE
Affiliation:
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
JEFFREY A. STANLEY
Affiliation:
Departments of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan
VINCE D. CALHOUN
Affiliation:
The Mind Research Network, Albuquerque, New Mexico Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, New Mexico Department of Psychiatry, Yale University, Hartford, Connecticut
GODFREY D. PEARLSON
Affiliation:
Department of Psychiatry, Yale University, Hartford, Connecticut
JAY W. PETTEGREW*
Affiliation:
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania Department of Behavioral and Community Health Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania
*
*Correspondence and reprint requests to: Jay W. Pettegrew, M.D., Director, Neurophysics Laboratory, RIDC Park, 260 Kappa Drive, Pittsburgh, Pennsylvania, 15238. E-mail: pettegre+@pitt.edu

Abstract

Synaptic development and elimination are normal neurodevelopmental processes, which if altered could contribute to various neuropsychiatric disorders. 31P-1H magnetic resonance spectroscopic imaging (MRSI) and structural magnetic resonance imaging (MRI) exams were conducted on 105 healthy children ages 6–18 years old to identify neuromolecular indices of synaptic development and elimination. Over the age range studied, age-related changes in high-energy phosphate (phosphocreatine), membrane phospholipid metabolism (precursors and breakdown products), and percent gray matter volume were found. These neuromolecular and structural indices of synaptic development and elimination are associated with development of several cognitive domains. Monitoring of these molecular markers is essential for devising treatment strategies for neurodevelopmental disorders. (JINS, 2009, 15, 671–683.)

Type
Research Articles
Copyright
Copyright © The International Neuropsychological Society 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Agranoff, B.W., & Hajra, A.K. (1994). Lipids. In Siegel, G.J., Agranoff, B.W., Albers, R.W., & Molinoff, P.B. (Eds.), Basic neurochemistry: Molecular, cellular, and medical aspects (5th ed., pp. 97116). New York: Raven Press.Google Scholar
Andreasen, N.C., Endicott, J., Spitzer, R.L., & Winoker, G. (1977). The reliability and validity of the family history method using family history research diagnostic criteria (FH-RDC). Archives of General Psychiatry, 34, 12291235.CrossRefGoogle Scholar
Andres, R.H., Ducray, A.D., Schlattner, U., Wallimann, T., & Widmer, H.R. (2008). Functions and effects of creatine in the central nervous system. Brain Research Bulletin, 76, 329343.CrossRefGoogle ScholarPubMed
Bartha, R., Drost, D.J., Menon, R.S., & Williamson, P.C. (2000). Comparison of the quantification precision of human short echo time (1)H spectroscopy at 1.5 and 4.0 Tesla. Magnetic Resonance in Medicine, 44, 185192.3.0.CO;2-V>CrossRefGoogle ScholarPubMed
Birch, H.G., & Gussow, J.D. (1970). Disadvantaged children, health, and nutrition and school failure. New York: Harcourt, Brace & World.Google Scholar
Birken, D.L., & Oldendorf, W.H. (1989). n-Acetyl-l-aspartic acid: A literature review of a compound prominent in 1H-NMR spectroscopic studies of brain. Neuroscience and Biobehavioral Reviews, 13, 2331.CrossRefGoogle ScholarPubMed
Bottomley, P.A. (1987). Spatial localization in NMR spectroscopy in vivo. Annals of the New York Academy of Sciences, 508, 333348.CrossRefGoogle ScholarPubMed
Bourgeois, J.-P. & Rakic, P. (1993). Changes of synaptic density in the primary visual cortex of the Macaque monkey from fetal to adult stage. Journal of Neuroscience, 13, 28012820.CrossRefGoogle ScholarPubMed
Brockmann, K., Pouwels, P.J., Christen, H.J., Frahm, J., & Hanefeld, F. (1996). Localized proton magnetic resonance spectroscopy of cerebral metabolic disturbances in children with neuronal ceroid lipofuscinosis. Neuropediatrics, 27, 242248.CrossRefGoogle ScholarPubMed
Buchli, R., Martin, E., Boesiger, P., & Rumpel, H. (1994). Developmental changes of phosphorus metabolite concentrations in the human brain: A 31P magnetic resonance spectroscopy study in vivo. Pediatric Research, 35, 431435.CrossRefGoogle Scholar
Chugani, H.R., Phelps, M.E., & Mazziotta, J.C. (1987). Positron emission tomography study of human brain functional development. Annals of Neurology, 322, 487497.CrossRefGoogle Scholar
Cleveland, W.S. (1979). Robust locally-weighted regression and smoothing scatterplots. Journal of the American Statistical Association, 74, 829836.CrossRefGoogle Scholar
Cleveland, W.S., & Grosse, E. (1988). Regression by local fitting. Journal of Econometrics, 37, 87114.CrossRefGoogle Scholar
de Beer, R., & van Ormondt, D. (1992). Analysis of NMR data using time domain fitting procedures. In Diehl, P. & Fluck, E.G. (Eds.), NMR basics, principles and progress (pp. 201258). New York: Springer-Verlag.Google Scholar
deGraaf, A.A., & Bovee, W.M.M.J. (1990). Improved quantification of in vivo 1H NMR spectra by optimization of signal acquisition and processing and by incorporation of prior knowledge into the spectral fitting. Magnetic Resonance in Medicine, 15, 305319.CrossRefGoogle Scholar
Ebert, D., Speck, O., Konig, A., Berger, M., Hennig, J., & Hohagen, F. (1997). 1H-magnetic resonance spectroscopy in obsessive-compulsive disorder: Evidence for neuronal loss in the cingulate gyrus and the right striatum. Psychiatry Research, 74, 173176.CrossRefGoogle ScholarPubMed
Eeg-Olofsson, O., Kristensson, K., Sourander, P., & Svennerholm, L. (1966). Tay-Sach’s Disease. A generalized metabolic disorder. Acta Paediatrica Scandinavica, 55, 546562.CrossRefGoogle ScholarPubMed
Frahm, J., & Hanefeld, F. (1996). Localized proton magnetic resonance spectroscopy of cerebral metabolites. Neuropediatrics, 27, 6469.CrossRefGoogle ScholarPubMed
Frahm, J., Michaelis, T., Merboldt, K.D., Hanicke, W., Gyngell, M.L., & Bruhn, H. (1991). On the n-acetyl methyl resonance in localized 1H NMR spectra of human brain in vivo. Nuclear Magnetic Resonance in Biomedicine, 4, 201204.Google ScholarPubMed
Frey, K.A. (1994). Positron emission tomography. In Siegel, G.J., Agranoff, B.W., Albers, R.W., & Molinoff, P.B. (Eds.), Basic neurochemistry: Molecular, cellular and medical Aspects (5th ed., pp. 935955). New York: Raven Press.Google Scholar
Geddes, J.W., Panchalingam, K., Keller, J.N., & Pettegrew, J.W. (1997). Elevated phosphocholine and phosphatidyl choline following rat entorhinal cortex lesions. Neurobiology of Aging, 18, 305308.CrossRefGoogle ScholarPubMed
Giedd, J.N., Blumenthal, J., Jeffries, N.O., Castellanos, F.X., Liu, H., Zijdenbos, A., Paus, T., Evans, A.C., & Rapoport, J.L. (1999). Brain development during childhood and adolescence: A longitudinal MRI study. Nature Reviews Neuroscience, 2, 861863.CrossRefGoogle ScholarPubMed
Gogtay, N., Ordonez, A., Herman, D.H., Hayashi, K.M., Greenstein, D., Vaituzis, C., Lenane, M., Clasen, L., Sharp, W., Giedd, J.N., Jung, D., Nugent, T.F. III, Toga, A.W., Leibenluft, E., Thompson, P.M., & Rapoport, J.L. (2007). Dynamic mapping of cortical development before and after the onset of pediatric bipolar illness. Journal of Child Psychology & Psychiatry & Allied Disciplines, 48, 852862.CrossRefGoogle ScholarPubMed
Goldstein, F.B. (1959). Biosynthesis of n-acetyl-l-aspartic acid. Journal of Biological Chemistry, 234, 27022706.CrossRefGoogle Scholar
Goldstein, F.B. (1969). The enzymatic synthesis of n-acetyl-l-aspartic acid by subcellular preparations. Journal of Biological Chemistry, 244, 42574260.CrossRefGoogle ScholarPubMed
Hein, H., Krieglstein, J., & Stock, R. (1975). The effects of increased glucose supply and thiopental anesthesia on energy metabolism of the isolated perfused rat brain. Naunyn Schmiedebergs Archives of Pharmacology, 289, 399407.CrossRefGoogle ScholarPubMed
Hess, H. (1961). The rates of respiration of neurons and neuroglia in human cerebrum. In Kety, S.S. & Elkes, J. (Eds.), Regional neurochemistry (pp. 200202). Oxford, UK: Pergamon Press.Google Scholar
Huttenlocher, P.R. (1979). Synaptic density in human frontal cortex: Developmental changes and effects of aging. Brain Research, 163, 195205.Google ScholarPubMed
Huttenlocher, P.R. (1990). Morphometric study of human cerebral cortex development. Neuropsychologia, 28, 517527.CrossRefGoogle ScholarPubMed
Huttenlocher, P.R. & Dabholkar, A.S. (1997). Regional differences in synaptogenesis in human cerebral cortex. Journal of Comparative Neurology, 387, 167178.3.0.CO;2-Z>CrossRefGoogle ScholarPubMed
Huttenlocher, P.R., de Courtten, C., Garey, L.J., & Van der Loos, L.H. (1982). Synaptogenesis in human visual cortex: Evidence for synapse elimination during normal development. Neuroscience Letters, 33, 247252.CrossRefGoogle ScholarPubMed
Inglese, M., Rusinek, H., George, I.C., Babb, J.S., Grossman, R.I., & Gonen, O. (2008). Global average gray and white matter n-acetylaspartate concentration in the human brain. Neuroimage, 41, 270276.CrossRefGoogle ScholarPubMed
Jansson, S.E., Harkonen, M.H., & Helve, H. (1979). Metabolic properties of nerve endings isolated from rat brain. Acta Physiologica Scandinavica, 107, 205212.CrossRefGoogle ScholarPubMed
Kadekaro, M., Crane, A.M., & Sokoloff, L. (1985). Differential effects of electrical stimulation of sciatic nerve on metabolic activity in spinal cord and dorsal root ganglion in the rat. Proceedings of the National Academy of Sciences of the United States of America, 82, 60106013.CrossRefGoogle ScholarPubMed
Kennedy, C., & Sokoloff, L. (1957). An adaptation of the nitrous oxide method to the study of the cerebral circulation in children: Normal values for cerebral blood flow and cerebral metabolic rate in childhood. Journal of Clinical Investigation, 36, 11301137.CrossRefGoogle Scholar
Klunk, W.E., Xu, C.J., Panchalingam, K., McClure, R.J., & Pettegrew, J.W. (1994). Analysis of magnetic resonance spectra by mole percent: Comparison to absolute units. Neurobiology of Aging, 15, 133140.CrossRefGoogle ScholarPubMed
Knizley, H. (1967). The enzymatic synthesis of n-acetyl-l-aspartic acid by a water-insoluble preparation of a cat brain acetone powder. Journal of Biological Chemistry, 242, 46194622.Google ScholarPubMed
Koller, K.J., Zaczek, R., & Coyle, J. (1984). n-acetyl-aspartyl-glutamate: Regional levels in rat brain and the effects of brain lesions as determined by a new HPLC method. Journal of Neurochemistry, 43, 11361142.CrossRefGoogle ScholarPubMed
Kreis, R. (1997). Quantitative localized 1H MR spectroscopy for clinical use. Journal of Progress in Nuclear Magnetic Resonance, 31, 155195.CrossRefGoogle Scholar
McCandless, D.W., & Wiggins, R.C. (1981). Cerebral energy metabolism during the onset and recovery from halothane anesthesia. Neurochemical Research, 6, 13191326.CrossRefGoogle ScholarPubMed
McIlwain, H., & Bachelard, H.S. (1985). Biochemistry and the Central Nervous System (5th ed.). Edinburgh, UK: Churchill Livingstone.Google Scholar
Naglieri, J.A., LeBuffe, P.A., & Pfeiffer, S.I. (1994). Devereux Scale for Mental Disorders. San Antonio, TX: Psychological Corporation.Google Scholar
Pettegrew, J.W., Keshavan, M.S., Stanley, J.A., McClure, R.J., Johnson, C.R., & Panchalingam, K. (2003). Magnetic resonance spectroscopy in the assessment of phospholipid metabolism in schizophrenia and other psychiatric disorders. In Peet, M., Glen, I., & Horrobin, D.F. (Eds.), Phospholipid spectrum disorder in psychiatry (2nd ed., pp. 239255). Carnforth, UK: Marius.Google Scholar
Pouwels, P.J., & Frahm, J. (1997). Differential distribution of NAA and NAAG in human brain as determined by quantitative localized proton MRS. Nuclear Magnetic Resonance in Biomedicine, 10, 7378.Google ScholarPubMed
Provencher, S.W. (1993). Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magnetic Resonance in Medicine, 30, 672679.CrossRefGoogle ScholarPubMed
Rakic, P., Bourgeois, J.-P., Eckenhoff, M.F., Zecevic, N., & Goldman-Rakic, P.S. (1986). Concurrent overproduction of synapses in diverse regions of the primate cerebral cortex. Science, 232, 232235.CrossRefGoogle ScholarPubMed
Rango, M., Bozzali, M., Prelle, A., Scarlato, G., & Bresolin, N. (2001). Brain activation in normal subjects and in patients affected by mitochondrial disease without clinical central nervous system involvement: A phosphorus magnetic resonance spectroscopy study. Journal of Cerebral Blood Flow & Metabolism, 21, 8591.CrossRefGoogle ScholarPubMed
Rango, M., Castelli, A., & Scarlato, G. (1997). Energetics of 3.5 s neural activation in humans: A 31P MR spectroscopy study. Magnetic Resonance in Medicine, 38, 878883.CrossRefGoogle ScholarPubMed
Roux, L. (1998). Magnetic resonance. Journal of Magnetic Resonance Imaging, 8, 10221023.Google Scholar
Seeger, U., Klose, U., Mader, I., Grodd, W., & Nagele, T. (2003). Parameterized evaluation of macromolecules and lipids in proton MR spectroscopy of brain diseases. Magnetic Resonance in Medicine, 49, 1928.CrossRefGoogle ScholarPubMed
Siesjo, B.K. (1978). Brain energy metabolism. New York: Wiley.Google ScholarPubMed
Simmons, M.L., Frondoza, C.G., & Coyle, J.T. (1991). Immunocytochemical localization of n-acetyl-aspartate with monoclonal antibodies. Neuroscience, 45, 3745.CrossRefGoogle ScholarPubMed
Smiley, J.F., & Goldman-Rakic, P.S. (1993). Heterogeneous targets of dopamine synapses in monkey prefrontal cortex demonstrated by serial section electron microscopy: A laminar analysis using the silver enhanced diaminobenzidine-sulfide (SEDS) immunolabeling technique. Cerebral Cortex, 3, 223238.CrossRefGoogle ScholarPubMed
Smith, S.M., Jenkinson, M., Woolrich, M.W., Beckmann, C.F., Behrens, T.E.J., Johansen-Berg, H., Bannister, P.R., De Luca, M., Drobnjak, I., Flitney, D.E., Niazy, R., Saunders, J., Vickers, J., Zhang, Y., De Stefano, N., Brady, J.M., & Matthews, P.M. (2004). Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage, 23(Suppl. 1), 208219.CrossRefGoogle ScholarPubMed
Sokoloff, L. (1966). Cerebral circulatory and metabolic changes associated with aging. Research Publications – Association for Research in Nervous and Mental Disease, 41, 237254.Google ScholarPubMed
Sokoloff, L. (1991). Measurement of local cerebral glucose utilization and its relation to local functional activity in the brain. Advances in Experimental Medicine & Biology, 291, 2142.CrossRefGoogle ScholarPubMed
Sokoloff, L. (1993). Function-related changes in energy metabolism in the nervous system: Localization and mechanisms. Keio Journal of Medicine, 42, 95103.CrossRefGoogle ScholarPubMed
Stanley, J.A., Drost, D.J., Williamson, P.C., & Thompson, R.T. (1995). The use of a priori knowledge to quantify short echo in vivo 1H MR spectra. Magnetic Resonance in Medicine, 34, 1724.CrossRefGoogle Scholar
Stanley, J.A., & Pettegrew, J.W. (2001). Post-processing method to segregate and quantify the broad components underlying the phosphodiester spectral region of in vivo 31P brain spectra. Magnetic Resonance in Medicine, 45, 390396.3.0.CO;2-D>CrossRefGoogle Scholar
Storm-Mathisen, J., & Otterson, O.P. (1990). Immunocytochemistry of glutamate at the synaptic level. Journal of Histochemistry and Cytochemistry, 38, 17331743.CrossRefGoogle ScholarPubMed
Suzuki, K. (1966). The pattern of mammalian brain gangliosides III. Regional and developmental differences. Journal of Neurochemistry, 12, 969979.CrossRefGoogle Scholar
Tallan, H.H., Moore, S., & Stein, W.H. (1956). n-acetyl-l-aspartic acid in brain. Journal of Biological Chemistry, 219, 257264.CrossRefGoogle ScholarPubMed
Truckenmiller, M.E., Namboodiri, M.A.A., Brownstein, M.J., & Neale, J.H. (1985). n-Acetylation of l-aspartate in the nervous system: Differential distribution of a specific enzyme. Journal of Neurochemistry, 45, 16581662.CrossRefGoogle ScholarPubMed
Urenjak, J., Williams, S.R., Gadian, D.G., & Noble, M. (1993). Proton nuclear magnetic resonance spectroscopy unambiguously identifies different neural cell types. Journal of Neuroscience, 13, 981989.CrossRefGoogle ScholarPubMed
Volpe, J.J. (1995). Neuronal proliferation, migration, organization, and myelination. In Neurology of the newborn (3rd ed., pp. 4392). Philadelphia: W.B. Saunders.Google Scholar
Wechsler, D. (1974). Wechsler Intelligence Scale for Children-Revised manual. New York: Psychological Corporation.Google Scholar
Wechsler, D. (1999). WASI: Wechsler Abbreviated Scale of Intelligence manual. San Antonio, TX: Psychological Corporation.Google Scholar
Wechsler, D. (2001). Wechsler Individual Achievement Test (2nd ed.), San Antonio, TX: Psychological Corporation.Google Scholar
Whittaker, V.P. (1966). Some properties of synaptic membranes isolated from the central nervous system. Annals of the New York Academy of Sciences, 137, 982998.CrossRefGoogle ScholarPubMed
Wiegandt, H. (1967). The subcellular localization of gangliosides in the brain. Journal of Neurochemistry, 14, 671674.CrossRefGoogle ScholarPubMed
Woolrich, M.W., Jbabdi, S., Patenaude, B., Chappell, M., Makni, S., Behrens, T., Beckmann, C., Jenkinson, M., & Smith, S.M. (2009). Bayesian analysis of neuroimaging data in FSL. Neuroimage, 45(Suppl. 1), S173S186.CrossRefGoogle ScholarPubMed