BDNF mRNA expression and protein localization are changed in age-related hearing loss.
A decline in neuronal plasticity during the adult life span has been proposed to be associated with a reduced level of the effectors of plasticity responses (e.g., BDNF). Alteration of plasticity is also correlated with age-related hearing loss (presbycusis), but to date no detailed studies of BDNF expression have been performed in the young or aging mature cochlea. We have used rat and gerbil animal models for presbycusis, which displayed hearing loss in the final third of the animals' natural life span. We demonstrate for the first time a co-localization of BDNF protein, transcripts III and IV in cochlear neurons with a declining distribution towards low-frequency processing cochlear turns. BDNF protein was also found within the neuronal projections of the cochlea. A significant reduction of BDNF transcripts in high-frequency processing cochlear neurons was observed during aging, though this did not coincide with a major reduction of BDNF protein. In contrast, BDNF protein in peripheral and central projections was drastically reduced. Our results suggest that reduced BDNF protein levels in auditory nerves over age may be a crucial factor in the altered brainstem plasticity observed during presbycusis.
Rüttiger
Lukas
L
Molecular Neurobiology, Tübingen Hearing Research Center, Department of Otorhinolaryngology, University of Tübingen, Tübingen, Germany.
Panford-Walsh
Rama
R
Schimmang
Thomas
T
Tan
Justin
J
Zimmermann
Ulrike
U
Rohbock
Karin
K
Köpschall
Iris
I
Limberger
Annette
A
Müller
Marcus
M
Fraenzer
Jürgen-Theodor
JT
Cimerman
Jelka
J
Knipper
Marlies
M
D000367:Age Factors; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism*; D002452:Cell Count / Q000379:methods; D003051:Cochlea / Q000473:pathology; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D005455:Fluorescent Antibody Technique / Q000379:methods; D005786:Gene Expression Regulation / Q000502:physiology*; D005849:Gerbillinae; D017403:In Situ Hybridization / Q000379:methods; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D011304:Presbycusis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D020813:Receptor, trkB / Q000172:deficiency; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013136:Spiral Ganglion / Q000473:pathology
D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D020813:Receptor, trkB