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Versican Plays an Important Role in
Neural Development and Damage
Repair in the Cochlea
Meredith Hammer
The Governor’s School for Science and Mathematics
Mentor: Dr. Hainan Lang
Department of Pathology and Laboratory Medicine
The Medical University of South Carolina
The Cochlea
http://universalhealthcarela.com/photos-external-ear-anatomy/
The Organ of Corti
The Cochlea
The Organ Corti
Hearing Loss in Cochlea
 Sensory –occurs when the hair cells in the cochlea are damaged
 Neural – damage or degeneration in neurons of the auditory nerve
http://thehearingfix.com/types-of-hearing-loss/sensorineural-hearing-loss/
The Cochlea
The Organ Corti
Myelination and Nodes of Ranvier
http://bio1152.nicerweb.com/Locked/media/ch48/myelin.html
Neurons Communicate Using Action Potentials
http://apbrwww5.apsu.edu/thompsonj/
Anatomy%20&%20Physiology/2010/201
0%20Exam%20Reviews/Exam%203%20R
eview/CH%2011%20Action%20Potential
s.htm
Myelination and Nodes of Ranvier
http://home.apu.edu/~jsimons/Bio101/human1.htm
Versican (VCAN): Proteoglycan of the
Extracellular Matrix
• Proteoglycan: a protein/carbohydrate molecule
• VCAN is located around myelinated axons, specifically the Nodes of Ranvier
http://www.seehint.com/hint.asp?md=144&no=12735
Our Research
• We are interested in Versican because…
– Stress induced heart problems in VCAN V0/V2 knockout mice
– VCAN has not been studied in the cochlea
– VCAN accumulating in cochlea during postnatal development and injury
– VCAN KO and WT mice with similar hearing function before noise damage
• We are investigating its significance in the cochlea
by…
– Determining morphological differences between Versican V0/V2 knockout and
wild type mice
– Investigating the response of V0/V2 knockout mice to noise damage, in
comparison to wild type
Versican V0/V2 knockout mice
• Knockout mice compared with wild type
mice to investigate importance of
Versican in function and morphology
• Its V2 isoform has been studied
previously in the central nervous system
(Zimmermann, et. al.)
 Affected ECM organization and
structure
 Absence of Phosphocan and Tenascin-
R
 Did not affect myelination
• Versican function in cochlea has not
been determined
http://atlasgeneticsoncology.org/Genes/GC_VCAN.html
Hypothesis
Versican expression in the cochlea is required for
• maintaining the structural integrity of auditory nerve
• functional recovery from cochlear damage.
Using Transmission Electron Microscopy (TEM) to view
morphological differences between WT and KO mice
• Mice TEM samples were WT and KO before noise
exposure
Delamination and Irregularity in Myelination on Neuron Cell Bodies
KOWT
Deformity in Myelination and Structure at the Nodes of Ranvier
WT KO
Axonal and Myelin Changes in Myelinated Axons
WT KO
Testing auditory function with Auditory Brainstem
Response (ABR)
• The first peak of waveform Auditory nerve
Auditory Nerve
Obtaining hearing thresholds with Auditory Brainstem
Response (ABR)
• Tested thresholds from 4.0 to
45.2 kHz at 90 to 10 dB
Damaging the Cochlea with Noise Insult to Compare Recovery
• Noise insult: The octave-band of frequencies at 106 dB for 2
hours
ABR Recording Timeline to track Recovery
Threshold
Threshold
Shift
Threshold Shifts of WT and Versican KO mice
Conclusions
• Our audiograms signify a lack of recovery in the auditory nerve for
Versican knockout mice.
• Our TEM samples show delamination, axonal changes and other
irregularity of neuron structure in the knockout mice that may
cause the variances in recovery between WT and KO mice.
• These differences in morphology and threshold shift between WT
and KO mice suggest that Versican is important in damage recovery
and structural regularity in the auditory nerve.
Further Analysis of our Data
• How can better show that the
Versican KO mice are detecting less
sound after damage?
– Versican KO and WT mice have similar
thresholds
– Comparing amplitude of the first waveform
between KO and WT mice that can be
obtained from ABR results
• Investigate regression of recovery
for Versican KO mice
– Run statistical analysis for each mouse
Acknowledgements
o Dr. Hainan Lang
o Lab members
 Yazhi Xing, LaShardai Conaway, Clarisse
Panganiban, Xin Liu, Andy Sheng, Kenyaria
Noble, Juhong Shu
o Nancy Smythe - TEM
o Dr. Mjaatvet Corey – VCAN mice
o Department of Pathology and Laboratory
Medicine
o The Medical University of South Carolina
o Randy LaCross and Christina Belis (SPRI)
o Dr. Jennifer Taylor
Questions

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Meredith Hammer - Presentation Colloquium

  • 1. Versican Plays an Important Role in Neural Development and Damage Repair in the Cochlea Meredith Hammer The Governor’s School for Science and Mathematics Mentor: Dr. Hainan Lang Department of Pathology and Laboratory Medicine The Medical University of South Carolina
  • 3. The Organ of Corti The Cochlea The Organ Corti
  • 4. Hearing Loss in Cochlea  Sensory –occurs when the hair cells in the cochlea are damaged  Neural – damage or degeneration in neurons of the auditory nerve http://thehearingfix.com/types-of-hearing-loss/sensorineural-hearing-loss/ The Cochlea The Organ Corti
  • 5. Myelination and Nodes of Ranvier http://bio1152.nicerweb.com/Locked/media/ch48/myelin.html
  • 6. Neurons Communicate Using Action Potentials http://apbrwww5.apsu.edu/thompsonj/ Anatomy%20&%20Physiology/2010/201 0%20Exam%20Reviews/Exam%203%20R eview/CH%2011%20Action%20Potential s.htm
  • 7. Myelination and Nodes of Ranvier http://home.apu.edu/~jsimons/Bio101/human1.htm
  • 8. Versican (VCAN): Proteoglycan of the Extracellular Matrix • Proteoglycan: a protein/carbohydrate molecule • VCAN is located around myelinated axons, specifically the Nodes of Ranvier http://www.seehint.com/hint.asp?md=144&no=12735
  • 9. Our Research • We are interested in Versican because… – Stress induced heart problems in VCAN V0/V2 knockout mice – VCAN has not been studied in the cochlea – VCAN accumulating in cochlea during postnatal development and injury – VCAN KO and WT mice with similar hearing function before noise damage • We are investigating its significance in the cochlea by… – Determining morphological differences between Versican V0/V2 knockout and wild type mice – Investigating the response of V0/V2 knockout mice to noise damage, in comparison to wild type
  • 10. Versican V0/V2 knockout mice • Knockout mice compared with wild type mice to investigate importance of Versican in function and morphology • Its V2 isoform has been studied previously in the central nervous system (Zimmermann, et. al.)  Affected ECM organization and structure  Absence of Phosphocan and Tenascin- R  Did not affect myelination • Versican function in cochlea has not been determined http://atlasgeneticsoncology.org/Genes/GC_VCAN.html
  • 11. Hypothesis Versican expression in the cochlea is required for • maintaining the structural integrity of auditory nerve • functional recovery from cochlear damage.
  • 12. Using Transmission Electron Microscopy (TEM) to view morphological differences between WT and KO mice • Mice TEM samples were WT and KO before noise exposure
  • 13. Delamination and Irregularity in Myelination on Neuron Cell Bodies KOWT
  • 14. Deformity in Myelination and Structure at the Nodes of Ranvier WT KO
  • 15. Axonal and Myelin Changes in Myelinated Axons WT KO
  • 16. Testing auditory function with Auditory Brainstem Response (ABR) • The first peak of waveform Auditory nerve Auditory Nerve
  • 17. Obtaining hearing thresholds with Auditory Brainstem Response (ABR) • Tested thresholds from 4.0 to 45.2 kHz at 90 to 10 dB
  • 18. Damaging the Cochlea with Noise Insult to Compare Recovery • Noise insult: The octave-band of frequencies at 106 dB for 2 hours
  • 19. ABR Recording Timeline to track Recovery Threshold Threshold Shift
  • 20. Threshold Shifts of WT and Versican KO mice
  • 21. Conclusions • Our audiograms signify a lack of recovery in the auditory nerve for Versican knockout mice. • Our TEM samples show delamination, axonal changes and other irregularity of neuron structure in the knockout mice that may cause the variances in recovery between WT and KO mice. • These differences in morphology and threshold shift between WT and KO mice suggest that Versican is important in damage recovery and structural regularity in the auditory nerve.
  • 22. Further Analysis of our Data • How can better show that the Versican KO mice are detecting less sound after damage? – Versican KO and WT mice have similar thresholds – Comparing amplitude of the first waveform between KO and WT mice that can be obtained from ABR results • Investigate regression of recovery for Versican KO mice – Run statistical analysis for each mouse
  • 23. Acknowledgements o Dr. Hainan Lang o Lab members  Yazhi Xing, LaShardai Conaway, Clarisse Panganiban, Xin Liu, Andy Sheng, Kenyaria Noble, Juhong Shu o Nancy Smythe - TEM o Dr. Mjaatvet Corey – VCAN mice o Department of Pathology and Laboratory Medicine o The Medical University of South Carolina o Randy LaCross and Christina Belis (SPRI) o Dr. Jennifer Taylor

Editor's Notes

  1. Should I include auditory nerve in title??
  2. http://thehearingfix.com/types-of-hearing-loss/sensorineural-hearing-loss/ [IMAGE] http://kidshealth.org/kid/health_problems/sight/hearing_impairment.html# [INFORMATION]
  3. Node first, then versican Cochlea or auditory nerve Stress induced heart issues… noise stress??
  4. Auditory nerve, vestibulocochlear nerve, or cochlea
  5. Double layer
  6. Describe how it works - Two electrodes??16
  7. Note that day 30 it goes back up (thresholds) for the knockout
  8. Where can we get the lab pictures????