losartan-potassium and Presbycusis

The present study aimed to determine the expression of erythropoietin (EPO) and the EPO receptor (EPOR) in spiral ganglion neurons (SGNs) in the inner ear of rats of various ages, and the associated neuronal apoptosis and hearing alterations. A total of 15 healthy rats (n=30 ears), were divided into three groups: i) A nominated infant group at post‑natal day (PND) 12‑14, ii) an adult group at PND 60 and iii) a 3‑year postnatal aged group. Auditory brainstem response (ABR) measurements were performed on all rats. EPO and EPOR expression in the inner ear was detected by immunohistochemistry. In situ terminal deoxynucleotidyl transferase dUTP nick end labeling assays were performed to detect the apoptosis of SGNs. The average hearing thresholds of the ABR (decibels above normal hearing level) were 5.625±4.955 in the infant, 15.000±8.498 in the adult and 23.500±13.134 in the aged groups. Hearing thresholds for aged and adult rats increased significantly compared with infant rats. However, the difference in latencies of peak I was not significant (P>0.05). EPO in SGNs was detected during different developmental periods without significant alterations, but were reduced compared with Corti's organ or the stria vascularis. EPOR expression increased significantly from infant to adult stage, and this increased expression was maintained in the aged group. An age‑associated increase in the apoptosis of SGNs was detected in all three groups (P=0.0347). The potential neuroprotective effects of EPO in SGNs may not be revealed during the aging process under natural conditions, and may be associated with spontaneous neuronal apoptosis and consequently, hearing diminution. However, the age‑associated increase in EPOR in SGNs may exert a role in neuroprotection when necessary, for example in presbycusis.

Topics: Aging; Animals; Apoptosis; Ear, Inner; Erythropoietin; Female; Hearing Loss; Hearing Tests; Immunohistochemistry; Male; Neurons; Presbycusis; Rats; Rats, Sprague-Dawley; Receptors, Erythropoietin; Spiral Ganglion

So far, typical causes of presbycusis such as degeneration of hair cells and/or primary auditory (spiral ganglion) neurons cannot be treated. Because erythropoietin's (Epo) neuroprotective potential has been shown previously, we determined hearing thresholds of juvenile and aged mice overexpressing Epo in neuronal tissues. Behavioral audiometry revealed in contrast to 5 months of age, that 11-month-old Epo-transgenic mice had up to 35 dB lower hearing thresholds between 1.4 and 32 kHz, and at the highest frequencies (50-80 kHz), thresholds could be obtained in aged Epo-transgenic only but not anymore in old C57BL6 control mice. Click-evoked auditory brainstem response showed similar results. Numbers of spiral ganglion neurons in aged C57BL6 but not Epo-transgenic mice were dramatically reduced mainly in the basal turn, the location of high frequencies. In addition, there was a tendency to better preservation of inner and outer hair cells in Epo-transgenic mice. Hence, Epo's known neuroprotective action effectively suppresses the loss of spiral ganglion cells and probably also hair cells and, thus, development of presbycusis in mice.

Topics: Animals; Erythropoietin; Evoked Potentials, Auditory; Gene Expression; Gene Expression Regulation, Developmental; Hair Cells, Auditory; Mice, Inbred C57BL; Mice, Transgenic; Nerve Degeneration; Neuroprotective Agents; Presbycusis; Spiral Ganglion