Correlation Between Serum Brain-Derived Neurotrophic Factor Level and An In Vivo Marker of Cortical Integrity

BACKGROUND Brain-derived neurotrophic factor (BDNF) signaling at synapses improves synaptic strengthening associated with learning and memory. In the present study we hypothesized that serum BDNF concentration is associated with in vivo level of cerebral N-acetylaspartate (NAA), a well established marker of neuronal integrity. METHODS In 36 healthy subjects BDNF serum concentration and absolute concentration of NAA together with other metabolites were measured by proton magnetic resonance spectroscopy (1H-MRS) in regions with high BDNF levels (anterior cingulate cortex [ACC], left hippocampus). Relationship between BDNF concentration and brain metabolites was studied in linear regression analysis with BDNF concentration as dependent variable and metabolite concentrations, age, and gender as predictor variables. RESULTS The BDNF serum concentrations were positively associated with the concentrations of NAA (T = 2.193, p = .037) and total choline (T = 1.997, p = .055; trend) but not total creatine or glutamate in the ACC. No significant association was observed between BDNF serum concentration and absolute metabolite concentrations in the hippocampus. CONCLUSIONS The preliminary data might indicate that BDNF serum concentration reflects some aspects of neuronal plasticity as indicated by its association with NAA level in the cerebral cortex. The results would be in line with the notion that BDNF plays a central role in the regulation of neuronal survival and differentiation in the human brain.

[1]  B. Lu,et al.  Regulation of synaptic responses to high-frequency stimulation and LTP by neurotrophins in the hippocampus , 1996, Nature.

[2]  D. Auer,et al.  Hippocampal metabolic abnormalities in mild cognitive impairment and Alzheimer's disease , 2005, Neuroscience Letters.

[3]  M. Tosetti,et al.  Proton magnetic resonance spectroscopy (1H-MRS) of motor cortex and basal ganglia in de novo Parkinson's disease patients , 2001, Neurological Sciences.

[4]  D. Sheehan,et al.  The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. , 1998, The Journal of clinical psychiatry.

[5]  M. Egan,et al.  Brain-Derived Neurotrophic Factor val66met Polymorphism Affects Human Memory-Related Hippocampal Activity and Predicts Memory Performance , 2003, The Journal of Neuroscience.

[6]  Juha E. A. Knuuttila,et al.  The effects of acute and long-term lithium treatments on trkB neurotrophin receptor activation in the mouse hippocampus and anterior cingulate cortex , 2006, Neuropharmacology.

[7]  Margit Burmeister,et al.  BDNF Val66Met Allele Is Associated with Reduced Hippocampal Volume in Healthy Subjects , 2006, Biological Psychiatry.

[8]  R. Saunders,et al.  The relationship between dorsolateral prefrontal N-acetylaspartate measures and striatal dopamine activity in schizophrenia∗ ∗ See accompanying Editorial, in this issue. , 1999, Biological Psychiatry.

[9]  K Ugurbil,et al.  In vivo 1H NMR spectroscopy of the human brain at 7 T , 2001, Magnetic resonance in medicine.

[10]  Mu-ming Poo,et al.  Neurotrophins as synaptic modulators , 2001, Nature Reviews Neuroscience.

[11]  G. Barker,et al.  1H magnetic resonance spectroscopy of chronic cerebral white matter lesions and normal appearing white matter in multiple sclerosis , 1997, Journal of neurology, neurosurgery, and psychiatry.

[12]  Jürgen Gallinat,et al.  Association between cerebral glutamate and human behaviour: The sensation seeking personality trait , 2007, NeuroImage.

[13]  P Boesiger,et al.  Detection of glutathione in the human brain in vivo by means of double quantum coherence filtering , 1999, Magnetic resonance in medicine.

[14]  T. Hergueta,et al.  The mini international neuropsychiatric interview , 1998, European Psychiatry.

[15]  A. Granholm,et al.  Frontal cortex BDNF levels correlate with working memory in an animal model of Down syndrome , 2003, Behavioural Brain Research.

[16]  H. Danker-Hopfe,et al.  Serum neurotrophins—A study on the time course and influencing factors in a large old age sample , 2007, Neurobiology of Aging.

[17]  C. Bramham,et al.  The coupling of a trkB tyrosine residue to LTP , 2003, Trends in Neurosciences.

[18]  Elena Cattaneo,et al.  Progressive loss of BDNF in a mouse model of Huntington's disease and rescue by BDNF delivery. , 2005, Pharmacological research.

[19]  H. Phillips,et al.  Widespread expression of BDNF but not NT3 by target areas of basal forebrain cholinergic neurons. , 1990, Science.

[20]  M. Ozkan,et al.  Quantitative proton MR spectroscopic findings of cortical reorganization in the auditory cortex of musicians. , 2005, AJNR. American journal of neuroradiology.

[21]  J. Krystal,et al.  Sex, GABA, and nicotine: The impact of smoking on cortical GABA levels across the menstrual cycle as measured with proton magnetic resonance spectroscopy , 2005, Biological Psychiatry.

[22]  C. Elster,et al.  Quantitative magnetic resonance spectroscopy: Semi‐parametric modeling and determination of uncertainties , 2005, Magnetic resonance in medicine.

[23]  Jürgen Gallinat,et al.  Glutamate concentrations in human brain using single voxel proton magnetic resonance spectroscopy at 3 Tesla , 2004, NeuroImage.

[24]  D. Ankerst,et al.  Neurochemical alterations of the brain in bipolar disorder and their implications for pathophysiology: A systematic review of the in vivo proton magnetic resonance spectroscopy findings , 2006, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[25]  G. Porcellati,et al.  Metabolism of Phosphoglycerides , 1983 .

[26]  O Henriksen,et al.  Absolute quantitative proton NMR spectroscopy based on the amplitude of the local water suppression pulse. Quantification of brain water and metabolites , 1994, NMR in biomedicine.

[27]  T Horinouchi,et al.  Development and aging of the cerebrum: assessment with proton MR spectroscopy. , 2001, AJNR. American journal of neuroradiology.

[28]  J. Ashburner,et al.  Multimodal Image Coregistration and Partitioning—A Unified Framework , 1997, NeuroImage.

[29]  J. Gorski,et al.  Early Striatal Dendrite Deficits followed by Neuron Loss with Advanced Age in the Absence of Anterograde Cortical Brain-Derived Neurotrophic Factor , 2004, The Journal of Neuroscience.

[30]  R. Menon,et al.  Comparison of the quantification precision of human short echo time 1H spectroscopy at 1.5 and 4.0 Tesla , 2000, Magnetic resonance in medicine.

[31]  Ravi S. Menon,et al.  Glutamate and glutamine measured with 4.0 T proton MRS in never-treated patients with schizophrenia and healthy volunteers. , 2002, The American journal of psychiatry.

[32]  M. Giroud,et al.  N‐Acetylaspartate: a literature review of animal research on brain ischaemia , 2004, Journal of neurochemistry.

[33]  William A Banks,et al.  Transport of brain-derived neurotrophic factor across the blood–brain barrier , 1998, Neuropharmacology.

[34]  D. Senkowski,et al.  Hippocampal glutamate concentration predicts cerebral theta oscillations during cognitive processing , 2006, Psychopharmacology.

[35]  J. Kleinman,et al.  Reduced brain-derived neurotrophic factor in prefrontal cortex of patients with schizophrenia , 2003, Molecular Psychiatry.

[36]  Kevin G Bath,et al.  Variant BDNF (Val66Met) impact on brain structure and function , 2006, Cognitive, affective & behavioral neuroscience.

[37]  Lars G. Hanson,et al.  Evaluation of CA1 damage using single-voxel 1H-MRS and un-biased stereology: Can non-invasive measures of N-acetyl-asparate following global ischemia be used as a reliable measure of neuronal damage? , 2001, Brain Research.

[38]  Jürgen Gallinat,et al.  Association of human hippocampal neurochemistry, serotonin transporter genetic variation, and anxiety , 2005, NeuroImage.

[39]  G. Lynch,et al.  Restoration of long-term potentiation in middle-aged hippocampus after induction of brain-derived neurotrophic factor. , 2006, Journal of neurophysiology.

[40]  T. Ebisu,et al.  N-Acetylaspartate as an in vivo Marker of Neuronal Viability in Kainate-Induced Status Epilepticus: 1H Magnetic Resonance Spectroscopic Imaging , 1994, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[41]  E Moser,et al.  Proton T 1 and T 2 relaxation times of human brain metabolites at 3 Tesla , 2001, NMR in biomedicine.

[42]  Daniel Senkowski,et al.  Frontal and Temporal Dysfunction of Auditory Stimulus Processing in Schizophrenia , 2002, NeuroImage.

[43]  R. Kreis.  Issues of spectral quality in clinical 1H‐magnetic resonance spectroscopy and a gallery of artifacts , 2004, NMR in biomedicine.

[44]  Karl J. Friston,et al.  Investigations of the functional anatomy of attention using the stroop test , 1993, Neuropsychologia.

[45]  Jürgen Gallinat,et al.  Association of BDNF Serum Concentrations with Central Serotonergic Activity: Evidence from Auditory Signal Processing , 2005, Neuropsychopharmacology.

[46]  M. Schwald,et al.  Postnatal developmental profile of brain-derived neurotrophic factor in rat brain and platelets , 2002, Neuroscience Letters.

[47]  Takashi Asada,et al.  The Val66Met polymorphism of the brain-derived neurotrophic factor gene affects age-related brain morphology , 2006, Neuroscience Letters.

[48]  Dae-Shik Kim,et al.  High-field magnetic resonance techniques for brain research , 2003, Current Opinion in Neurobiology.

[49]  H. Danker-Hopfe,et al.  Differential regulation of nerve growth factor and brain-derived neurotrophic factor in a mouse model of learned helplessness , 2006, Experimental Neurology.

[50]  R. Hellweg,et al.  Neuroprotection and neuronal dysfunction upon repetitive inhibition of oxidative phosphorylation , 2003, Experimental Neurology.

[51]  J. Eichberg.  Phospholipids in nervous tissues , 1985 .

[52]  R. Gruetter,et al.  1H NMR detection of vitamin C in human brain in vivo , 2004, Magnetic resonance in medicine.

[53]  J. Campusano,et al.  Functional interactions between somatodendritic dopamine release, glutamate receptors and brain-derived neurotrophic factor expression in mesencephalic structures of the brain , 2004, Brain Research Reviews.

[54]  S. Zeiler,et al.  Development/Plasticity/Repair Brain-Derived Neurotrophic Factor Is Required for the Maintenance of Cortical Dendrites , 2022 .

[55]  Rex E. Jung,et al.  Sex differences in N-acetylaspartate correlates of general intelligence: An 1H-MRS study of normal human brain , 2005, NeuroImage.

[56]  J. Kleinman,et al.  BDNF and trkB mRNA expression in the hippocampus and temporal cortex during the human lifespan. , 2006, Gene expression patterns : GEP.

[57]  N. Szeverenyi,et al.  Cognitive interference is associated with neuronal marker N-acetyl aspartate in the anterior cingulate cortex: an in vivo 1H-MRS study of the Stroop Color-Word task , 2001, Molecular Psychiatry.

[58]  Núria Bargalló,et al.  Medial temporal MR spectroscopy is related to memory performance in normal adolescent subjects , 2004, Neuroreport.

[59]  Q. Luo,et al.  BDNF Acutely Modulates Synaptic Transmission and Calcium Signalling in Developing Cortical Neurons , 2005, Cellular Physiology and Biochemistry.

[60]  J. Virchow,et al.  The impact of age, weight and gender on BDNF levels in human platelets and plasma , 2004, Neurobiology of Aging.

[61]  M. Egan,et al.  The BDNF val66met Polymorphism Affects Activity-Dependent Secretion of BDNF and Human Memory and Hippocampal Function , 2003, Cell.

[62]  K Maeda,et al.  Abnormal expression of brain-derived neurotrophic factor and its receptor in the corticolimbic system of schizophrenic patients , 2000, Molecular Psychiatry.

[63]  E. Levine,et al.  Brain‐derived neurotrophic factor increases activity of NR2B‐containing N‐methyl‐D‐aspartate receptors in excised patches from hippocampal neurons , 2000, Journal of neuroscience research.