Neuronal Activity in a Model of Noise Induced Tinnitus: A Longitudinal Study

Details

• Personal Author:
  Apawu A ; Berkowitz B ; Cacace A ; Ghoddoussi F ; Hali M ; Holt A ; Muca A ; Wilson S
• Description:
  Background: Tinnitus, "ringing in the ears", is the number one service related disability for Veterans. Currently, no objective biomarkers exist for tinnitus. We have previously demonstrated that both noise- and drug-induced tinnitus result in behavioral deficits in Gap inhibition of the acoustic startle reflex (GiASR) 48 hours following tinnitus induction. Manganese-enhanced MRI (MEMRI) uses the paramagnetic manganese (Mn2+) ion, a contrast agent and calcium channel probe, to assess calcium channel linked neuronal activity. Tinnitus has been associated with increases in neuronal activity, and we have previously reported increases in Mn2+ uptake in the inferior colliculus (IC) following acute tinnitus induction. We tested the hypothesis that enhanced manganese uptake (MEMRI) will be positively correlated with Gap detection deficits (GiASR) over time. Methods: In male Sprague Dawley rats, Mn2+ uptake was assessed in 12 regions of interest (ROIs) from MEMRI data (n = 10/group) before, and 1, 28, and 84 day(s) following acoustic trauma (16 kHz, 106 dB SPL, 1 hour). ASR testing was performed twice per week in the same animals across six frequencies (4, 8, 12, 16, 20 and 24 kHz). Each animal was administered a non-toxic dose of 66 mg/kg of MnCl2 (i.p) 24 hours prior to each imaging session (7T Clinscan). In a subgroup of rats, Mn2+ clearance from ROIs was measured after 1, 14, 28, 42 and 84 day(s). Results: All animals had unimpaired pre-pulse ASR responses before and after noise exposure. Deficits in Gap detection were evident in noise animals at all time points except the first week after noise exposure (20 kHz, 60 dB). In contrast to our previous findings in acute models of tinnitus, later time points in this study demonstrated supernormal Mn2+ uptake in the paraflocculus at 4 (14% greater) and 12 (7% greater) weeks. Twelve weeks following noise exposure the IC and medial geniculate body also exhibited significant increases in Mn2+ uptake. The clearance rate of Mn2+ was found to be similar between subdivisions of the IC at all examined time points. Conclusions: The present data further strengthen our hypothesis that chronic tinnitus without permanent hearing loss is associated with increases in calcium channel linked neuronal activity. Differential uptake in brain regions may have initially been associated with hearing loss and later with tinnitus, paralleling the progression of a temporary threshold shift. These results suggest the need for longitudinal assessment of tinnitus progression using MEMRI and GiASR biomarkers when evaluating therapeutic intervention. [Description provided by NIOSH]
• Subjects:
  Animals Biomarkers Manganese Nervous System Noise Noise, Occupational Occupational Health Safety
• Keywords:
  Animal Studies Auditory System Ear Disorders Neurological System Neuropathology Noise Exposure 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:20060981
• Citation:
  Abstr Midwinter Res Meet Assoc Res Otolaryngol 2016 Feb; 39:594-595
• CAS Registry Number:
  Manganese (CAS RN 7439-96-5)
• 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:abf6b652eabb6af43c6b12a7a794210d080548c3050c6434296d1b25b14f333c4e1e241ae6c21ceae8b938e462fa7f05f0cd04a742967f45c5fac698b82876a9
• Download URL:
  https://stacks.cdc.gov/view/cdc/224697/cdc_224697_DS1.pdf
• File Type:
  [PDF - 835.03 KB ]