Genetic Progressive Hearing Loss in the C57/M6 Mouse: Relation of Behaviorial Responses to Cochlear Anatomy

Mikaelian, Diran O.; Warfield, Dickens; Norris, Olga

doi:10.3109/00016487409124632

Cited by 94 publications

(35 citation statements)

References 6 publications

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“…This indicates that fear learning in adult BDNF +/2 mice is only impaired, but not completely abolished. Furthermore, this rescue experiment also excludes that the observed learning deficit is due to alterations in sensory systems, like an acceleration of the hearing loss that is described for C57BL/6 mice, starting at 3 mo of age (Mikaelian et al 1974). A similar rescue effect of an increasing number of CS -US pairings was also reported for TrkB-signalingdeficient mice (Musumeci et al 2009).…”

Section: Fear Learning In Bdnfsupporting

confidence: 49%

Age-dependent deficits in fear learning in heterozygous BDNF knock-out mice

Endres

Leßmann

2012

Learn. Mem.

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Beyond its trophic function, the neurotrophin BDNF (brain-derived neurotrophic factor) is well known to crucially mediate synaptic plasticity and memory formation. Whereas recent studies suggested that acute BDNF/TrkB signaling regulates amygdala-dependent fear learning, no impairments of cued fear learning were reported in heterozygous BDNF knockout mice (BDNF +/2 ). Since brain BDNF levels are known to decline with aging, we hypothesized that BDNF +/2 mice might show reduced fear learning at older ages. Indeed, BDNF +/2 animals revealed an age-dependent deficit in fear learning 3 mo after birth and beyond. Since there were no alterations between the two genotypes during the conditioning training and when testing short-term memory, this learning deficit most likely reflects a deficit in memory consolidation. Importantly, there were no differences in spontaneous motor behavior and baseline anxiety in BDNF +/2 animals at any age tested. Following behavioral testing quantification of BDNF levels in the basolateral amygdala with a sensitive BDNF ELISA revealed a positive correlation between the levels of BDNF in the amygdala and the individual learning performance. However, the age-dependent decline in the efficiency of fear conditioning in BDNF +/2 mice was not accompanied by reduced BDNF expression in the amygdala. Thus, while reduced BDNF levels in general correlate with less efficient fear learning, this lack of BDNF can be compensated in young but not in older animals, suggesting that the cellular mechanisms responsible for fear learning consolidation become BDNF-dependent 3 mo after birth.

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Section: Fear Learning In Bdnfsupporting

confidence: 49%

Age-dependent deficits in fear learning in heterozygous BDNF knock-out mice

Endres

Leßmann

2012

Learn. Mem.

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“…Thus the P18 -25 age range chosen for this study falls before age-related hearing loss occurs in this strain yet shows measures of threshold and sensitivity that are comparable to those of the adult mouse (Song et al, 2006). Furthermore, the behavioral threshold for C57/Bl6 mice at older ages of 2-4 months is reported as 40 dB SPL for 40 kHz and 35 dB for 8 kHz, making the 75-dB level employed in this study of P18 -25 animals well above threshold (Mikaelian et al, 1974).…”

Section: Auditory Thresholdsmentioning

confidence: 92%

Auditory brainstem neural activation patterns are altered in EphA4‐ and ephrin‐B2‐deficient mice

Miko

Nakamura

Henkemeyer

et al. 2007

J of Comparative Neurology

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Auditory processing requires proper formation of tonotopically ordered projections. We have evaluated the role of an Eph receptor tyrosine kinase and an ephrin ligand in the development of these frequency maps. We demonstrated expression of EphA4 and ephrin-B2 in auditory nuclei and found expression gradients along the frequency axis in neonates. We tested the roles of EphA4 and ephrin-B2 in development of auditory projections by evaluating whether mutations result in altered patterns of expression of the immediate early gene c-fos after exposure to pure tone stimuli. We evaluated two nuclei, the dorsal cochlear nucleus (DCN) and the medial nucleus of the trapezoid body (MNTB), which project in two distinct auditory pathways. The mean number of c-fos-positive neurons in EphA4(-/-) DCN after 8-kHz pure tone stimulation was 42% lower than in wild-type DCN. Along the dorsoventral, tonotopic axis of DCN, the mean position of c-fos-positive neurons was similar for mutant and wild-type mice, but the spread of these neurons along the tonotopic axis was 35% greater for ephrin-B2(lacZ/+) mice than for wild-type mice. We also examined these parameters in MNTB after exposure to 40-kHz pure tones. Both EphA4(-/-) and ephrin-B2(lacZ/+) mice had significantly fewer c-fos-positive cells than wild-type littermates. The labeled band of cells was narrower and laterally shifted in EphA4(-/-) mice compared with wild-type mice. These differences in cell number and distribution suggest that EphA4 and ephrin-B2 signaling influence auditory activation patterns.

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“…Indeed, the head-tilt mice appear to have normal hearing (677). However, as these studies were performed in C57BL/6 mice, which are characterized by a severe, early hearing loss (607,826), further studies on this topic are necessary.…”

Section: Inner Earmentioning

confidence: 99%

The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology

Bedard¹,

Krause²

2007

Physiological Reviews

5,931

117

5,778

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For a long time, superoxide generation by an NADPH oxidase was considered as an oddity only found in professional phagocytes. Over the last years, six homologs of the cytochrome subunit of the phagocyte NADPH oxidase were found: NOX1, NOX3, NOX4, NOX5, DUOX1, and DUOX2. Together with the phagocyte NADPH oxidase itself (NOX2/gp91phox), the homologs are now referred to as the NOX family of NADPH oxidases. These enzymes share the capacity to transport electrons across the plasma membrane and to generate superoxide and other downstream reactive oxygen species (ROS). Activation mechanisms and tissue distribution of the different members of the family are markedly different. The physiological functions of NOX family enzymes include host defense, posttranlational processing of proteins, cellular signaling, regulation of gene expression, and cell differentiation. NOX enzymes also contribute to a wide range of pathological processes. NOX deficiency may lead to immunosuppresion, lack of otoconogenesis, or hypothyroidism. Increased NOX actvity also contributes to a large number or pathologies, in particular cardiovascular diseases and neurodegeneration. This review summarizes the current state of knowledge of the functions of NOX enzymes in physiology and pathology.

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Genetic Progressive Hearing Loss in the C57/M6 Mouse: Relation of Behaviorial Responses to Cochlear Anatomy

Cited by 94 publications

References 6 publications

Age-dependent deficits in fear learning in heterozygous BDNF knock-out mice

Age-dependent deficits in fear learning in heterozygous BDNF knock-out mice

Auditory brainstem neural activation patterns are altered in EphA4‐ and ephrin‐B2‐deficient mice

The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology

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