Neurochemical Profiles from the Auditory Cortex of Rats with Behavioral Evidence of Tinnitus: Assessment with High Resolution Magic-Angle Spinning Proton Magnetic Resonance Spectroscopy

Details

• Personal Author:
  Cacace A ; Galloway M ; Ghoddoussi F ; Holt AG
• Description:
  Based on advancements in tinnitus research over the last 3 decades, it is reasonable to suggest that a prominent theory of tinnitus neuropathology subsumes a neurochemical basis. This view is consistent with converging evidence that partial or complete peripheral deafferentation from acoustic trauma results in a cascade of changes in the peripheral and central nervous system that induces an imbalance between inhibitory and excitatory inputs to auditory neurons at various levels in the auditory pathways. Male Sprague Dawley rats were divided into noise-exposed and non noise-exposed groups; auditory thresholds and Gap detection assessments were determined for each group both before and after exposure to a tone (16 kHz, 106 dB SPL, 1 hr). Neurochemical profiles were determined one month after noise-exposure with high resolution magic angle spinning proton magnetic resonance spectroscopy (HR-MAS 1 H-MRS) at 11.7T ex vivo. Frozen tissue samples (4-7 mg) were placed into a zirconium rotor containing 8 uL of buffer (pH = 7.4), then into a Bruker 11.7T Avance 500 MHz spectrometer maintained at 4 degrees C, spun at 4.2 kHz, at a spatial orientation of 54.7 degrees (the magic angle) relative to the longitudinal magnetic field (Bo ). Tissue spectra were acquired with a Carr-Purcell-Meiboom-Gill (CPMG) echo train acquisition sequence. Concentrations of MR visible metabolites were corrected for tissue weight and were expressed as nmol/mg tissue weight. Using HR-MAS 1 H-MRS, we obtained unbiased neurochemical profiles of intact auditory cortex tissue from noise-exposed animals with behavioral evidence of tinnitus. We found significant increases in alanine (ALA, +41%) and glutathione (GSH, +43%) as well a decrease in glycerophosphorylcholine (GPC, -19%) and their corresponding ratios to total creatine. Although the absence of changes in glutamate, glutamine, and GABA argue against putative lesions in the auditory cortex of noise-exposed animals, elevated ALA is consistent with increased transamination of pyruvate (i.e., the end-product of glycolysis) or increased decarboxylation of aspartate. Similarly, increases in GSH, the major antioxidant in the brain, may represent a compensatory response to cellular oxidative stress. Decreases in GPC, generated during the production of inflammatory mediators from membrane phospholipids, may reflect decreased production of inflammatory lipids or increased demand for GPC in membrane phospholipid biosynthesis. Overall, the results suggest neuroplasticity as measured by 1 H-MRS in auditory cortex from an animal model of noise-induced tinnitus, possibly associated with disrupted pyruvate metabolism, oxidative stress, and membrane phospholipid turnover. Future studies will focus on neurochemical changes in other brain regions-of-interest. [Description provided by NIOSH]
• Subjects:
  Animals Nervous System Noise Noise, Occupational Occupational Health Safety
• Keywords:
  Animal Studies Auditory System Brain Function Ear Disorders Neurological System Neuropathology Noise Exposure Oxidative Stress Tinnitus
• ISSN:
  0742-3152
• Publisher:
  Association for Research in Otolaryngology
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; Michigan ; OSHA Region 5 ; OSHA Region 9
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  39
• NIOSHTIC Number:
  nn:20060979
• Citation:
  Abstr Midwinter Res Meet Assoc Res Otolaryngol 2016 Feb; 39:594
• Federal Fiscal Year:
  2016
• Performing Organization:
  University of Michigan, Ann Arbor
• Peer Reviewed:
  False
• Start Date:
  20050701
• Source Full Name:
  Abstracts of the 39th Midwinter Research Meeting of the Association for Research in Otolaryngology, Febuary 20-24, 2016, San Diego, California
• End Date:
  20280630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:8b035133bdc56a5c02a8851f86a31aa4a8fd72567a0758ea72cd42ad219def1faa2186abebe628c1175cdd74bf34a950fb9120950788458c7230a079549c1ae2
• Download URL:
  https://stacks.cdc.gov/view/cdc/224695/cdc_224695_DS1.pdf
• File Type:
  [PDF - 829.03 KB ]