**3.6 Spiral ganglion cells and auditory dendrites**

Keithley et al. (1989) compared the density of spiral ganglion cells in young and old gerbils. The mean ganglion cell density averaged along the whole cochlea was 1106 cells/mm² for 4 gerbils with an age of 2 months. Compared to the mean of these young gerbils, the density decreased to 86% and 83% in 5 animals aged 24-30 months and in 3 animals aged 36-42 months respectively, though the difference between the young animals and the 2 groups of old animals was not significant in this sample. When they compared mean spiral ganglion cell density for separate half turns of the cochlea, a significant reduction that varied between 16 and 55% in the two groups of old gerbils with reference to the 2 month old animals was only found for the most basal position (80-90% from the apical end, corresponding to frequencies above 20 kHz). Overall, the loss of spiral ganglion cells was limited and predominantly affected high frequencies.

Based on a small sample that precluded statistical analysis, Suryadevara et al. (2001) suggested a slightly decreased number of auditory dendrites per inner hair cell in old gerbils. Their data in young gerbils showed a gradient of auditory nerve fibre dendrite

The Mongolian Gerbil as a Model for

and strial degeneration.

pathology explained only up to 37% of the EP variation.

**3.7.3 Changes in enzymes regulating potassium homeostasis** 

paralleled those reported for the Na,K-ATPase.

the Analysis of Peripheral and Central Age-Dependent Hearing Loss 73

function have been the focus of several studies (Gratton & Schulte, 1995; Gratton et al., 1996, 1997b; Sakaguchi et al., 1997a, 1997b; Thomopoulos et al., 1997). Gratton & Schulte (1995) described small regions at the apical and basal ends of the SV that were devoid of capillaries in gerbils as young as 5-10 months. With increasing age, loss of capillaries progressed from both ends towards the middle of the cochlea. Gerbils older than 33 months showed a normal pattern of strial vascularisation only in the mid-region of the cochlea. In the regions of capillary loss, strial atrophy was observed with missing marginal cells and "clumps of pigment" in remaining cells. Gratton et al. (1996) found a significant correlation between the proportion of the SV with normal vascularisation and the EP. However, due to the large inter-animal variability of both parameters, the correlation coefficient indicated that SV

In addition to loss of vascularisation and atrophy of the SV, different types of fibrocytes in the spiral ligament of old gerbils are also affected. Spicer & Schulte (2002) suggested that vacuolisation of type II fibrocytes in regions of old cochleae that show no strial atrophy can be regarded as an early event in the development of strial pathology. Regions with apoptotic or necrotic type II fibrocytes were associated with moderate degeneration of SV, while regions with a complete absence of type II fibrocytes showed advanced SV atrophy. Also, type IV and V fibrocytes showed vacuolisation in old gerbils, while type I fibrocytes did not. Thus, vacuolisation was found in Na,K-ATPase positive fibrocyte types II, IV and V, but not in negative type I fibrocytes. Unfortunately the hearing status was not known and could not be directly correlated with the degree of structural changes in these specimen. Based on their data, Spicer & Schulte (2002) put forward the hypothesis that, within the potassium recycling pathway, impaired secretion of potassium into the endolymph by strial marginal cells could reduce the flow of potassium towards the stria and lead to potassium accumulation and the development of vacuoles in Na,K-ATPase positive fibrocytes. They proposed that dysfunction of marginal cells is the first step leading to fibrocyte pathology

Spicer et al. (1997) compared the Na,K-ATPase-immunoreactivity (an ion exchange enzyme that uses ATP to pump 3 sodium ions out of the cell in exchange for 2 potassium ions that are pumped into the cell) in the lateral wall and SV of young and old gerbils. Immunostaining in cochleae of old gerbils was more variable than in young gerbils. Old animals showed strial atrophy and no Na,K-ATPase immunoreactivity at the apex, best preservation of SV and immunoreactivity in the middle, and atrophy of SV and loss of immunoreactivity at the base of the cochlea. Immunoreactivity in type II, IV and V fibrocytes of old gerbils decreased less than expression in the adjacent SV, although complete SV degeneration was also associated with loss of immunoreactivity in fibrocytes. The observation that a loss of Na,K-ATPase immunoreactivity in fibrocytes of the spiral ligament appeared to lag behind the loss of staining in the SV supports the suggestion that changes in fibrocytes occur secondarily to alterations in the SV. Sakaguchi et al. (1998) found that age-dependent changes in the expression of the Na-K-Cl co-transporter closely

Schulte & Schmiedt (1992) determined the Na,K-ATPase immunoreactive volume of the SV from immunostained cochlear sections. A plot of the EP as a function of the normalised SV

diameter within the osseous spiral lamina, with increasing diameter from the scala vestibuli to the scala tympani side. With decreasing endocochlear potential (EP) in old gerbils, this gradient disappeared due to fewer large diameter fibres found near scala tympani. In addition, the cross-sectional area of spiral ganglion cells decreased with decreasing EP. Thus, decreasing EP was associated with a loss or shrinkage of large diameter auditory nerve fibre dendrites and a reduction of the size of spiral ganglion cells.

Rüttiger et al. (2007) found an age dependent reduction of BDNF mRNA expression in high frequency spiral ganglion cells. In contrast, BDNF protein expression was preserved in the cochlear ganglion cells of old gerbils but declined in their central and peripheral processes.
