Correlation between Choline Signal Intensity and Acetylcholine Level in Different Brain Regions of Rat

Acetylcholine is an important excitatory neurotransmitter, which plays a crucial role in synaptic transmission. The level of acetylcholine is decreased in the early stages of Alzheimer disease (AD), the most common neurodegenerative disease. Therefore, measurement of acetylcholine in the brain may help the clinical diagnosis of AD. However, the methods used till now to detect the brain acetylcholine level are invasive, which are neither recommended nor acceptable in the clinic. Acetylcholine is synthesized from choline-containing compounds (Cho), the latter can be estimated by noninvasive proton magnetic resonance spectroscopy (1H MRS). To explore whether the Cho signal intensity could be used to represent the acetylcholine level in the brain, we employed 1H MRS to detect the Cho signal, and simultaneously, we also used microdialysis and high-performance liquid chromatography (HPLC) to measure the level of acetylcholine in hippocampus, striatum, frontal cortex, and somatosensory barrel field (S1BF cortex) of rats, respectively. The results showed that the correlations between Cho signal intensity and acetylcholine level in hippocampus, striatum, frontal cortex, and S1BF cortex were, respectively, 0.823 (p = 0.044), 0.851 (p = 0.032), 0.817 (p = 0.047), and 0.822 (p = 0.045). The F-values of the regression model were, respectively, 8.404 (p = 0.044), 10.47 (p = 0.032), 8.000 (p = 0.047), and 8.326 (p = 0.045). And the derived regression equations were y = 0.67x + 1.363 (hippocampus), y = 5.398x + 6.684 (striatum), y = 0.656x + 0.564 (frontal cortex), and y = 0.394x + 1.127 (S1BF cortex), respectively (y means acetylcholine, and x means Cho). These data suggest that the Cho signal intensity observed by 1H MRS may be used as an indicator of acetylcholine level in different brain regions of the rats.

[1]  M. Bakovic,et al.  Choline Transport for Phospholipid Synthesis , 2006 .

[2]  David G. Gadian,et al.  Nuclear magnetic resonance and its applications to living systems , 1982 .

[3]  M. Giovannini,et al.  Serotonergic modulation of acetylcholine release from cortex of freely moving rats. , 1998, The Journal of pharmacology and experimental therapeutics.

[4]  D. Selkoe Alzheimer's Disease Is a Synaptic Failure , 2002, Science.

[5]  B. Hoebel,et al.  Extracellular acetylcholine is increased in the nucleus accumbens following the presentation of an aversively conditioned taste stimulus , 1995, Brain Research.

[6]  P. Calabresi,et al.  Acetyl-l-carnitine protects striatal neurons against in vitro ischemia: The role of endogenous acetylcholine , 2006, Neuropharmacology.

[7]  M. Miranda,et al.  Cortical cholinergic activity is related to the novelty of the stimulus , 2000, Brain Research.

[8]  J. Coyle,et al.  Alzheimer's disease and senile dementia: loss of neurons in the basal forebrain. , 1982, Science.

[9]  P. E. Gold Acetylcholine modulation of neural systems involved in learning and memory , 2003, Neurobiology of Learning and Memory.

[10]  M. Sarter,et al.  Differential cortical acetylcholine release in rats performing a sustained attention task versus behavioral control tasks that do not explicitly tax attention , 2002, Neuroscience.

[11]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[12]  W. Greenough,et al.  Synaptic plasticity in cortical systems , 1999, Current Opinion in Neurobiology.

[13]  E. Giacobini Invited Review Cholinesterase inhibitors for Alzheimer’s disease therapy: from tacrine to future applications , 1998, Neurochemistry International.

[14]  K. Blennow,et al.  CSF markers for pathogenic processes in Alzheimer’s disease: diagnostic implications and use in clinical neurochemistry , 2003, Brain Research Bulletin.

[15]  C. Gong,et al.  Injection of okadaic acid into the meynert nucleus basalis of rat brain induces decreased acetylcholine level and spatial memory deficit , 2004, Neuroscience.

[16]  Alexei R. Koudinov,et al.  Direct detection of brain acetylcholine synthesis by magnetic resonance spectroscopy , 2005, Brain Research.

[17]  I. Grundke‐Iqbal,et al.  Tau pathology in Alzheimer disease and other tauopathies. , 2005, Biochimica et biophysica acta.

[18]  S. Arnold,et al.  A preclinical view of cholinesterase inhibitors in neuroprotection: do they provide more than symptomatic benefits in Alzheimer's disease? , 2005, Trends in pharmacological sciences.

[19]  M. Ragozzino Acetylcholine actions in the dorsomedial striatum support the flexible shifting of response patterns , 2003, Neurobiology of Learning and Memory.

[20]  M. Mesulam The cholinergic lesion of Alzheimer's disease: pivotal factor or side show? , 2004, Learning & memory.

[21]  H. Wiśniewski,et al.  Microtubule-associated protein tau. A component of Alzheimer paired helical filaments. , 1986, The Journal of biological chemistry.

[22]  Stanley J. Watson,et al.  The rat brain in stereotaxic coordinates (2nd edn) by George Paxinos and Charles Watson, Academic Press, 1986. £40.00/$80.00 (264 pages) ISBN 012 547 6213 , 1987, Trends in Neurosciences.

[23]  J. Trojanowski,et al.  A68: a major subunit of paired helical filaments and derivatized forms of normal Tau. , 1991, Science.

[24]  Mathias Hoehn,et al.  Correlation between MR-spectroscopic rat hippocampal choline levels and phospholipase A2 , 2006, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry.

[25]  P. Cras,et al.  Neuronal and microglial involvement in beta-amyloid protein deposition in Alzheimer's disease. , 1990, The American journal of pathology.

[26]  S. Ando,et al.  Enhancement of learning capacity and cholinergic synaptic function by carnitine in aging rats , 2001, Journal of neuroscience research.

[27]  Brian D. Ross,et al.  Magnetic Resonance Spectroscopy Diagnosis of Neurological Diseases , 1999 .

[28]  A. Persico,et al.  Activity of L-carnitine and L-acetylcarnitine on cholinoceptive neocortical neurons of the rat in vivo , 2005, Journal of Neural Transmission / General Section JNT.

[29]  R. Quirion,et al.  Alzheimer’s disease and the basal forebrain cholinergic system: relations to β-amyloid peptides, cognition, and treatment strategies , 2002, Progress in Neurobiology.

[30]  H. Wiśniewski,et al.  Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[31]  F. LaFerla,et al.  Alzheimer's disease: Aβ, tau and synaptic dysfunction , 2005 .

[32]  T. Robbins,et al.  Central cholinergic systems and cognition. , 1997, Annual review of psychology.

[33]  J. S. Benton,et al.  Choline acetyltransferase activity and histopathology of frontal neocortex from biopsies of demented patients , 1982, Journal of the Neurological Sciences.

[34]  Michael Garwood,et al.  In vivo visualization of Alzheimer's amyloid plaques by magnetic resonance imaging in transgenic mice without a contrast agent , 2004, Magnetic resonance in medicine.

[35]  A. Imperato,et al.  Acetyl-l-carnitine enhances acetylcholine release in the striatum and hippocampus of awake freely moving rats , 1989, Neuroscience Letters.

[36]  P. Davies,et al.  SELECTIVE LOSS OF CENTRAL CHOLINERGIC NEURONS IN ALZHEIMER'S DISEASE , 1976, The Lancet.

[37]  Clifford R Jack,et al.  Monitoring disease progression in transgenic mouse models of Alzheimer's disease with proton magnetic resonance spectroscopy. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[38]  Y. Boulanger,et al.  Role of phospholipase A2 on the variations of the choline signal intensity observed by 1H magnetic resonance spectroscopy in brain diseases 1 1 Published on the World Wide Web on 10 August 2000. , 2000, Brain Research Reviews.

[39]  R. Quirion,et al.  Alzheimer's disease and the basal forebrain cholinergic system: relations to beta-amyloid peptides, cognition, and treatment strategies. , 2002, Progress in neurobiology.

[40]  Frank M LaFerla,et al.  Alzheimer's disease: Abeta, tau and synaptic dysfunction. , 2005, Trends in molecular medicine.