Medial olivocochlear efferent terminals are protected by sound conditioning

Synaptophysin immunoreactivity was used as a marker for the olivocochlear efferent system that innervates the outer hair cells of the cochlea. An intense noise exposure at either 6.3 kHz or 1.0 kHz caused a significant reduction in anti-synaptophysin immunoreactivity within the 8–6 mm or 14–11 mm distance from the round window, respectively. In the region of the main lesion, the reduction in synaptophysin immunoreactivity for both the 6.3 and 1.0 kHz exposures correlated well with outer hair cell loss. In regions peripheral to the main lesion, some remnants of efferent nerve endings could remain even when their associated outer hair cells were missing. Pre-treatment with a low level sound conditioner (either at 6.3 tone or 1.0 kHz) effectively reduced the efferent and outer hair cell pathology induced by the 6.3 and 1.0 kHz intense noise exposures, respectively. The results demonstrate the feasibility of using anti-synaptophysin immunoreactivity as an effective means of quantifying pathological alterations to the medial cochlear efferent terminals throughout the cochlea. Furthermore, the results show that sound conditioning significantly reduces damage to the efferent terminals.     

Developmental changes of distortion product and transient evoked otoacoustic emissions in different age groups

The developmental changes of distortion product otoacoustic emissions (DPOAEs) and transient evoked otoacoustic emissions (TEOAEs) were evaluated in 275 normal subjects aged from 1 month to 39 years. The DP-grams showed an M-shaped pattern with peaks at 1587 Hz and 5042 Hz for all age groups. In subjects younger than 3 years, low frequency DPOAEs did not rise above the noise floor. The DP levels at high frequency (5042 Hz) did not change much from infancy to young adulthood (12.9-16.5 dB SPL), however, those at low and middle frequency significantly decreased with age. Total echo power (TEP) of TEOAE was greatest in early infancy, decreased rapidly before 6-7 years old, and then decreased gradually (TEP = 16.6 - 1.9 X ln (age)). Wave reproducibility was constant across age. The frequency area peak power (FAPP) to middle and high frequency sounds changed little with age, however, FAPP at low frequency sounds dramatically increased with age. FAPP at 5000 Hz was relatively depressed levels at each age. The TEOAE value was more prominent at middle and low frequencies while DPOAE was predominant at high frequencies. These two measurements may reflect different functions of outer hair cells in the developing cochlea.     

Vibratory stimulation increases and decreases the regional cerebral blood flow and oxidative metabolism: a positron emission tomography (PET) study

The aim of this study was to examine the hypothesis, if the activation of some cerebral structures due to physiological stimulation is accompanied by deactivations of other structures elsewhere in the brain. A vibratory stimulus was applied to the right hand palm of healthy volunteers and the regional cerebral blood flow (rCBF) and regional cerebral oxygen metabolism (rCMRO2) were measured with positron emission tomography (PET). Regional analysis and voxel-by-voxel plots indicated that the stimulation induced increases and decreases of the rCBF were coupled to increases and decreases of the rCMRO2. The increases were localized in the left primary somatosensory area (SI), the left secondary somatosensory area (SII), the left retroinsular field (RI), the left anterior parietal cortex, the left primary motor area (MI), and the left supplementary motor area (SMA). The decreases occurred bilaterally in the superior parietal cortex, in paralimbic association areas, and the left globus pallidus. The increases and decreases of the rCBF and rCMRO2 were balanced in such a way that the mean global CBF and CMRO2 did not change compared with rest. We conclude that the decreases of the cerebral oxidative metabolism indicated regional depressions of synaptic activity.     

Long-term sertraline treatment increases expression and decreases phosphorylation of glycogen synthase kinase-3B in platelets of patients with late-life major depression

BackgroundAbnormal regulation of glycogen synthase kinase 3-beta (GSK3B) activity has been implicated in the pathophysiology of mood disorders. Many pharmacological agents, including antidepressants, can modulate GSK3B. The aim of the present study was to investigate the effect of short-and long-term sertraline treatment on the expression and phosphorylation of GSK3B in platelets of patients with late-life major depression.MethodsThirty-nine unmedicated elderly adults with major depressive disorder (MDD) were initially included in this study. The comparison group comprised 18 age-matched, healthy individuals. The expression of total and Ser-9 phosphorylated GSK3B (pGSK3B) was determined by Enzyme Immunometric Assay (EIA) in platelets of patients and controls at baseline, and after 3 and 12 months of sertraline treatments for patients only. During this period, patients were continuously treated with therapeutic doses of sertraline. GSK3B activity was indirectly estimated by calculating the proportion of inactive (phosphorylated) forms (pGSK3B) in relation to the total expression of the enzyme (i.e., GSK3B ratio).ResultsDepressed patients had significantly higher levels of pGSK3B as compared to controls (p < 0.001). Within the MDD group, after 3 months of sertraline treatment no significant changes were observed in GSK3B expression and phosphorylation state, as compared to baseline levels. However, after 12 months of treatment we found a significant increase in the expression of total GSK3B (p = 0.05), in the absence of any significant changes in pGSK3B (p = 0.12), leading to a significant reduction in GSK3B ratio (p = 0.001).ConclusionsOur findings indicate that GSK3B expression was upregulated by the continuous treatment with sertraline, along with an increment in the proportion of active forms of the enzyme. This is compatible with an increase in overall GSK3B activity, which may have been induced by the long-term treatment of late-life depression with sertraline.