Calcium binding protein immunoreactivity in the central auditory system and correlations with the auditory periphery : the effects of noise and aging in mice

This study has examined how calcium binding protein immunoreactivity is modulated in the cochlear nucleus and the inferior colliculus after noise exposure and during aging in mice. The effect of noise exposure on calbindin-D28k (calbindin) and parvalbumin immunoreactivity in the dorsal and posteroventral cochlear nucleus (DCN and PVCN) and inferior colliculus (IC) was studied in CBA/CBA mice by using two-dimensional quantification. Moderate sound stimulation caused a graded increase in the expression of calbindin and parvalbumin immunoreactivity in the DCN and IC, and parvalbumin immunoreactivity in the PVCN. This increased immunoreactivity related to sound exposure suggests the appearance of additional neurons which express these proteins after sound stimulation. These findings implicate that these neurons have the possibility to react against trauma, and display calbindin or parvalbumin as a rescue event.

The effect of aging on parvalbumin, calbindin-D28k, and calretinin immunoreactivity, as well as the total neuronal number in the DCN and PVCN in aging CBA/CaJ (CBA) and C57BL/6J (C57) mice was studied. The CBA mouse strain is a useful model of late-onset presbyacusis, while the C57 mouse strain makes an excellent model of the early-onset of age-related sensorineural hearing loss. By using the unbiased quantitative stereological method, the total neuronal number and the total number of these calcium binding proteins has been determined in the DCN and PVC. An agerelated increase in the total number of parvalbumin and calbindin immunopositive neurons was demonstrated in the DCN at a time when a significant loss of neurons is noticed in the same region in CBA mice. Furthermore, an age- related increase of parvalbumin in the PVCN was observed, while the total number did not differ between young and old CBA mice. The mechanisms by which these calcium binding proteins may affect neurons during aging are not known, but it is presumably that impaired Ca2+ homeostasis might have a critical role in the cellular aging process. In C57 mice, an age-related decrease in the total number of neurons in the PVCN and DCN was found, without any significant changes in the total number of these calcium binding proteins. On the other hand, an increase of the percentage of parvalbumin in the PVCN and DCN, calbindin in the PVCN, and calretinin in the DCN was demonstrated. The reason for this increase might be because of the new synthesis of these calcium binding proteins in the previously 'silent' neurons, due to age-related alterations in Ca2+ homeostasis.

Peripheral pathology was correlated to the percentage of pavalbumin, calbindin and calretinin immunopositive neurons in the DCN and PVCN in aging CBA and C57 mice. A progressive peripheral cell loss was reflected in an increased expression of parvalbumin and calretinin in the DCN of CBA mice and C57 mice. Interestingly, a major difference between CBA and C57 mice was demonstrated in the PVCN, where only C57 mice showed a positive correlation between the percentage of calbindin in the PVCN and the progressive degenerative changes in the auditory periphery. These findings imply that the pathophysiological status of the auditory periphery may influence the neuronal homeostasis in the cochlear nucleus.

List of scientific papers

I. Idrizbegovic E, Bogdanovic N, Canlon B (1998). "Modulating calbindin and parvalbumin immunoreactivity in the cochlear nucleus by moderate noise exposure in mice. . A quantitative study on the dorsal and posteroventral cochlear nucleus. " Brain Res 800(1): 86-96
https://pubmed.ncbi.nlm.nih.gov/9685593

II. Idrizbegovic E, Bogdanovic N, Canlon B (1999). "Sound stimulation increases calcium-binding protein immunoreactivity in the inferior colliculus in mice. " Neurosci Lett 259(1): 49-52
https://pubmed.ncbi.nlm.nih.gov/10027553

III. Idrizbegovic E, Canlon B, Bross LS, Willott JF, Bogdanovic N (2001). "The total number neurons and calcium binding protein-positive neurons during aging in the cochlear nucleus of CBA/CaJ mice: A quantitative study." Hearing Research (In Print)

IV. Idrizbegovic E, Viberg A, Bogdanovic N, Canlon B (2001). "Peripheral cell loss related to calcium binding protein immunocytochemistry in the dorsal cochlear nucleus in CBA/CaJ mice during aging." Audiology & Neuro-Otology (In Print)

V. Idrizbegovic E, Bogdanovic N, Viberg A, Canlon B (2001). "Age-related correlation between peripheral auditory pathology and calcium binding protein immunoreactivity in the cochlear nucleus of C57BL/6J mice." (Manuscript)