Comparative examination of inner ear in wild type and pituitary adenylate cyclase activating polypeptide (PACAP)-deficient mice.
Pituitary adenylate cyclase activating polypeptide (PACAP) is a multifunctional neuropeptide with well-known neuroprotective and neurotrophic effects. The involvement of PACAP in sensory processing has also been documented, but little is known about its effects in the auditory system. PACAP and its specific receptor (PAC1) are present in the cochlea and in brain structures involved in auditory pathways. Recently, we have shown that PACAP protects cochlear cells against oxidative stress-induced apoptosis. The endolymphatic Ca(2+) concentration controlled by Ca(2+) buffers of the hair cells is essential for the normal hearing processes. In this study we examined the localization of PAC1 receptor and Ca(2+) buffering proteins (parvalbumin, calretinin, calbindin) in the inner ear of 5-day-old PACAP-deficient mice compared with wild-type mice in order to get a closer insight into the effect of endogenous PACAP in the cochlear function. We did not find differences in the distribution pattern of PAC1 receptors between the two groups, but wild-type animals showed significantly higher PAC1 receptor expression. In contrast, inner and outer hair cells of PACAP-deficient mice showed more pronounced parvalbumin, calbindin, and calretinin immunopositivity compared with wild-type mice. Elevated endolymphatic Ca(2+) is deleterious for cochlear function, while the high concentration of Ca(2+) buffers in hair cells may offer protection. The increased immunoreactivity of Ca(2+) binding proteins in the absence of PACAP provide further evidence the important role of PACAP in the hearing processes.
Department of Anatomy, PTE-MTA Lendulet PACAP Research Team, Medical School, University of Pecs, Szigeti ut 12, Pecs 7624, Hungary. andreatamassz@gmail.com
A
A
Tamas
K
K
Szabadfi
A
A
Nemeth
B
B
Fulop
P
P
Kiss
T
T
Atlasz
R
R
Gabriel
H
H
Hashimoto
A
A
Baba
N
N
Shintani
Zs
Z
Helyes
D
D
Reglodi
D000818:Animals; D064032:Calbindin 2; D064026:Calbindins; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D003051:Cochlea / Q000378:metabolism; D007758:Ear, Inner / Q000166:cytology / Q000378:metabolism*; D006198:Hair Cells, Auditory / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D010320:Parvalbumins / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics / Q000502:physiology*; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000378:metabolism*; D064030:S100 Calcium Binding Protein G / Q000378:metabolism
C576511:Calb2 protein, mouse; D064032:Calbindin 2; D064026:Calbindins; D002135:Calcium-Binding Proteins; D010320:Parvalbumins; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D064030:S100 Calcium Binding Protein G