Functional Magnetic Resonance Study of Non-conventional Morphological Brains: malnourished rats

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Malnutrition during brain development can cause serious problems that can be irreversible. Dysfunctional patterns of brain activity can be detected with functional MRI. We used BOLD functional Magnetic Resonance Imaging (fMRI) to investigate region differences of brain activity between control and malnourished rats. The food-competition method was applied to a rat model to induce malnutrition during lactation. A 7T magnet was used to detect changes of the BOLD signal associated with changes in brain activity caused by the trigeminal nerve stimulation in malnourished and control rats. Major neuronal activation was observed in malnourished rats in several brain regions, including cerebellum, somatosensory cortex, hippocampus, and hypothalamus. Statistical analysis of the BOLD signals from various brain areas revealed significant differences in somatosensory cortex between the control and experimental groups, as well as a significant difference between the cerebellum and other structures in the experimental group. This study, particularly in malnourished rats, demonstrates increased BOLD activation in the cerebellum.

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  • [1] Medina M.T. Amador C. Hernandez-Toranzo R. Hesse H. Holden K.R. Morales-Ortı́z A. Rodriguez-Salinas L.C. (2008). Neurologic Consequences of Malnutrition. New York: Demos Medical Publishing.

  • [2] Zeman F.J. Heng H. Hoogenboom E.R. Kavlock R.J. Mahboob S. (1986). Cell number and size in selected organs of fetuses of rats malnourished and exposed to nitrofen. Teratogenesis Carcinogenesis and Mutagenesis 6 (4) 339-347.

  • [3] Fukuda M.T.H. Francolin-Silva A.L. Sousa Almeida S. (2002). Early postnatal protein malnutrition affects learning and memory in the distal but not in the proximal cue version of the Morris water maze. Behavioural Brain Research 133 (2) 271-277.

  • [4] Lister J.P. Blatt G.J. DeBassio W.A. Kemper T.L. Tonkiss J. Galler J.R. Rosene D.L. (2005). Effect of prenatal protein malnutrition on numbers of neurons in the principal cell layers of the adult rat hippocampal formation. Hippocampus 15 (3) 393-403.

  • [5] Hillman D.E. Chen S. (1981). Vulnerablity of cerebellar development in malnutrition-I. Quantation of layer volume and neuron numbers. Neuroscience 6 (7) 1249-1262.

  • [6] Benitez-Bribiesca L. De la Rosa-Alvarez I. Mansilla-Olivares A. (1999). Dendritic spine pathology in infants with severe protein-calorie malnutrition. Pediatrics 104 (2) e21.

  • [7] Reddy P.V. Das A. Sastry P.S. (1979). Quantitative and compositional changes in myelin of undernourished and protein malnourished rat brains. Brain Research 161 (2) 227-235.

  • [8] Montanha-Rojas E.A. Ferreira A.A. Tenorio F. Barradas P.C. (2005). Myelin basic protein accumulation is impaired in a model of protein deficiency during development. Nutritional Neuroscience 8 (1) 49-56.

  • [9] Mazer C. Muneyyirci J. Taheny K. Raio N. Borella A. Whitaker-Azmtia P. (1997). Serotonin depletion during synaptogenesis leads to decreased synaptic density and learning deficits in the adult rat: A possible model of neurodevelopmental disorders with cognitive deficits. Brain Researc 760 (1-2) 68-73.

  • [10] Chen J.C. Turiak G. Galler J. Volicer L. (1997). Postnatal changes of brain monoamine levels in prenatally malnourished and control rats. International Journal of Developmental Neuroscience 15 (2) 257-263.

  • [11] Chang Y.M. Galler J.R. Luebke J.I. (2003). Prenatal protein malnutrition results in increased frequency of miniature inhibitory postsynaptic currents in rat CA3 interneurons. Nutritional Neuroscience 6 (4) 263-267.

  • [12] Nakagawasai O. (2005). Behavioral and neurochemical alterations following thiamine deficiency in rodents: Relationship to functions and cholinergic neurons. Yakugaku Zasshi 125 (7) 549 -554.

  • [13] Cermak J.M. Holler T. Jackson D.A. Blusztajn J.K. (1998). Prenatal availability of choline modifies development of the hippocampal cholinergic system. FASEB Journal 12 (3) 349-357.

  • [14] Zimmer L. Delpal S. Guilloteau D. Aioun J. Durand G. Chalon S. (2000). Chronic n-3 polyunsaturated fatty acid deficiency alters dopamine vesicle density in the rat frontal cortex. Neuroscience Letters 284 (1-2) 25-28.

  • [15] Chalon S. Vancassel S. Zimmer L. Guilloteau D. Durand G. (2001). Polyunsaturated fatty acids and cerebral function: Focus on monoaminergic neurotransmission. Lipids 36 (9) 937-944.

  • [16] Ortiz R. Cortes E. Perez L. Gonzalez C. Betancourt M. (1996). Assessment of an experimental method to induce malnutrition by food competition during lactation. Medical Science Research 24 843-846.

  • [17] Just N. Petersen C. Gruetter R. (2010). BOLD responses to trigeminal nerve stimulation. Magnetic Resonance Imaging 28 (8) 1143-1151.

  • [18] Wegener S. Wong E.C. (2008). Longitudinal MRI studies in the isoflurane-anesthetized rat: Long-term effects of a short hypoxic episode on regulation of cerebral blood flow as assessed by pulsed arterial spin labelling. NMR in Biomedicine 21 (7) 696-703.

  • [19] Sicard K. Shen Q. Brevard M.E. Sullivan R. Ferris C.F. King J.A. Duong T.Q. (2003). Regional cerebral blood flow and BOLD responses in conscious and anesthetized rats under basal and hypercapnic conditions: Implications for functional MRI studies. Journal of Cerebral Blood & Flow Metabolism 23 (4) 472-481.

  • [20] Kim T. Masamoto K. Fukuda M. Vazquez A. Kim S.G. (2010). Frequency-dependent neural activity CBF and BOLD fMRI to somatosensory stimuli in isoflurane-anesthetized rats. Neuroimage 52 (1) 224-233.

  • [21] Vanhoutte G. Verhoye M. Van der Linden A. (2006). Changing body temperature affects the T2* signal in the rat brain and reveals hypothalamic activity. Magnetic Resonance in Medicine 55 (5) 1006-1012.

  • [22] Hyder F. Behar K.L. Martin M.A. Blamire A.M. Shulman R.G. (1994). Dynamic magnetic resonance imaging of the rat brain during forepaw stimulation. Journal of Cerebral Blood & Flow Metabolism 14 (4) 649-655.

  • [23] Yang X. Hyder F. Shulman R.G. (1996). Activation of single whisker barrel in rat brain localized by functional magnetic resonance imaging. Proceedings of the National Academy of Sciences USA 93 (1) 475-478.

  • [24] Sawiak S.J. Wood N.I. Williams G.B. Morton A.J. Carpenter T.A. (2009). SPMMouse: A new toolbox for SPM in the animal brain. In ISMRM 17th Scientific Meeting & Exhibition Honolulu US 18-24 April 2009. ISMRM 6264.

  • [25] Paxinos G. Watson Ch. (1998). The Rat Brain in Stereotaxic Coordinates 4th ed. Academic Press.

  • [26] Kandel E.R. (2000). Principles of Neural Science. McGraw-Hill.

  • [27] Segura B. Guadarrama J.C. Pratz G. Mercado V. Merchant H. Cintra L. Jimenez I. (2004). Conduction failure of action potentials in sensory sural nerves of undernourished rats. Neuroscience Letters 354 (3) 181-184.

  • [28] Silva A.C. Koretsky A.P. (2002). Laminar specificity of functional MRI onset times during somatosensory stimulation in rat. Proceedings of the National Academy of Sciences USA 99 (23) 15182-15187.

  • [29] Vandervliet E. Nagels G. Heinecke A. Van Hecke W. Leemans A. Sijbers J. Parizel P.M. (2006). On the cause and mechanisms of the negative BOLD response in fMRI. In ESMRMB 2006: 23rd Annual Scientific Meeting Warsaw Poland 21-23 September 2006. ESMRMB 624.

  • [30] Lindquist M.A. Meng Loh J.M. Atlas L.Y. Wager T.D. (2009). Modeling the hemodynamic response function in fMRI: Efficiency bias and mis-modeling. Neuroimage 45 (1 Suppl) S187-S198.

  • [31] Zumer J.M. Brookes M.J. Stevenson C.M. Francis S.T. Morris P.G. (2010). Relating BOLD fMRI and neural oscillations through convolution and optimal linear weighting. Neuroimage 49 (2) 1479-1489.

  • [32] Henson R. Friston K. (2007). Convolution models for fMRI. In Statistical Parametric Mapping: The Analysis of Functional Brain Images. Elsevier 178-192.

  • [33] Yeşilyurt B. Uğurbil K. Uludağ K. (2008). Dynamics and nonlinearities of the BOLD response at very short stimulus durations. Magnetic Resonance Imaging 26 (7) 853-862.

  • [34] Gunston G.D. Burkimsher D. Malan H. Sive A.A. (1992). Reversible cerebral shrinkage in kwashiorkor: An MRI study. Archives of Disease in Childhood 67 (8) 1030-1032.

  • [35] Birn R.M. Saad Z.S. Bandettini P.A. (2001). Spatial heterogeneity of the nonlinear dynamics in the FMRI BOLD response. Neuroimage 14 (4) 817-826.

  • [36] Sizonenko S.V. Babiloni C. de Bruin E.A. Isaacs E.B. Jonsson L.S. Kennedy D.O. Latulippe M.E. Hohajen M.H. Moreines J. Pietrini P. Walhovd K.B. Winwood R.J. Sijben J.W. (2013). Brain imaging and human nutrition: Which measures to use in intervention studies? British Journal of Nutrition 110 (1) S1-S30.

  • [37] Van Camp N. Verhoye M. Van der Linden A. (2006). Stimulation of the rat somatosensory cortex at different frequencies and pulse widths. NMR in Biomedicine 19 (1) 10-17.

  • [38] Bullmore E. Sporns O. (2009). Complex brain networks: Graph theoretical analysis of structural and functional systems. Nature Reviews Neuroscience 10 (3) 186-198.

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