Three-dimensional mouse cochlea imaging based on the modified Sca/eS using confocal microscopy

Urata, Shinji; Okabe, Shigeo

doi:10.1007/s12565-023-00703-z

Cited by 5 publications

(3 citation statements)

References 53 publications

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“…To investigate the mechanism of this early hearing loss found in the AD mice, we performed gene expression analysis by NanoString Technologies using the mouse cochlea 49 and auditory cortex 50 ( Fig. 3A ) from 3xTgAD and 3xTgAD/Polβ +/− male mice.…”

Section: Resultsmentioning

confidence: 99%

Early-Onset Hearing Loss in Mouse Models of Alzheimer’s Disease and Increased DNA Damage in the Cochlea

Bohr,

Park,

Sahbaz

et al. 2024

AgingBio

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There is considerable interest in whether sensory deficiency is associated with the development of Alzheimer’s disease (AD). Notably, the relationship between hearing impairment and AD is of high relevance but still poorly understood. In this study, we found early-onset hearing loss in two AD mouse models, 3xTgAD and 3xTgAD/Polβ +/− . The 3xTgAD/Polβ +/− mouse is DNA repair deficient and has more humanized AD features than the 3xTgAD. Both AD mouse models showed increased auditory brainstem response (ABR) thresholds between 16 and 32 kHz at 4 weeks of age, much earlier than any AD cognitive and behavioral changes. The ABR thresholds were significantly higher in 3xTgAD/Polβ +/− mice than in 3xTgAD mice at 16 kHz, and distortion product otoacoustic emission signals were reduced, indicating that DNA damage may be a factor underlying early hearing impairment in AD. Poly ADP-ribosylation and protein expression levels of DNA damage markers increased significantly in the cochlea of the AD mice but not in the adjacent auditory cortex. Phosphoglycerate mutase 2 levels and the number of synaptic ribbons in the presynaptic zones of inner hair cells were decreased in the cochlea of the AD mice. Furthermore, the activity of sirtuin 3 was downregulated in the cochlea of these mice, indicative of impaired mitochondrial function. Taken together, these findings provide new insights into potential mechanisms for hearing dysfunction in AD and suggest that DNA damage in the cochlea might contribute to the development of early hearing loss in AD.

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Section: Resultsmentioning

confidence: 99%

Early-Onset Hearing Loss in Mouse Models of Alzheimer’s Disease and Increased DNA Damage in the Cochlea

Bohr,

Park,

Sahbaz

et al. 2024

AgingBio

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“…In recent years, there have been reports of immune system cells residing in the inner ear of humans and animals under steady-state conditions. These include lymphocytes, macrophages ( 35 , 36 ), neutrophils, B-, T-, NK-, myeloid cells ( 33 ), and mast cells ( 37 , 38 ). Immune cells can also infiltrate the cochlea from the periphery after noise exposure ( 39 ).…”

Section: Introductionmentioning

confidence: 99%

A systematic review of the clinical evidence for an association between type I hypersensitivity and inner ear disorders

Zeng,

Domarecka,

Kong

et al. 2024

Front. Neurol.

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Inner ear disorders have a variety of causes, and many factors can contribute to the exacerbation of cochlear and vestibular pathology. This systematic review aimed to analyze clinical data on the coexistence and potential causal interaction between allergic diseases and inner ear conditions. A search of PubMed and Web of Science identified 724 articles, of which 21 were selected for full-text analysis based on inclusion and exclusion criteria. The epidemiologic evidence found overwhelmingly supports an association between allergic disease and particular inner ear disorders represented by a high prevalence of allergic reactions in some patients with Ménière’s disease (MD), idiopathic sudden sensorineural hearing loss (ISSHL), and acute low-tone hearing loss (ALHL). In addition, patients with MD, ISSHL, and ALHL had higher levels of total serum IgE than healthy subjects. Finally, in some cases, changes in cochlear potential may have been induced by antigen exposure, while desensitization alleviated allergy and inner ear-related symptoms. The exact mechanism of interaction between the auditory/vestibular and immune systems is not fully understood, and further clinical and basic research is needed to understand the relationship between the two systems fully.

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“…Temporal bone 3D microanatomy is undergoing a renewed interest thanks to the availability of novel X-ray-based and fluorescence-based nondestructive methods of imaging (11). Although both imaging approaches produce similar results, fluorescence-based methods based on tissue clearing (12) allow labeling of cell populations or vascular and matrix components, which is essential for understanding physiological and pathological processes as well as immune cell distribution and interactions (13)(14)(15). In this study we mapped the 3D distribution of rat temporal bone marrow and its bone and vascular connections to the inner ear, dural and middle ear spaces, by employing iDISCO+ (16) based tissue clearing with immunostaining (13) and microCT.…”

Section: Introductionmentioning

confidence: 99%

Temporal bone marrow of the rat and its connections to the inner ear

Perin,

Cossellu,

Vivado

et al. 2024

Front. Neurol.

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Calvarial bone marrow has been found to be central in the brain immune response, being connected to the dura through channels which allow leukocyte trafficking. Temporal bone marrow is thought to play important roles in relation to the inner ear, but is still largely uncharacterized, given this bone complex anatomy. We characterized the geometry and connectivity of rat temporal bone marrow using lightsheet imaging of cleared samples and microCT. Bone marrow was identified in cleared tissue by cellular content (and in particular by the presence of megakaryocytes); since air-filled cavities are absent in rodents, marrow clusters could be recognized in microCT scans by their geometry. In cleared petrosal bone, autofluorescence allowed delineation of the otic capsule layers. Within the endochondral layer, bone marrow was observed in association to the cochlear base and vestibule, and to the cochlear apex. Cochlear apex endochondral marrow (CAEM) was a separated cluster from the remaining endochondral marrow, which was therefore defined as “vestibular endochondral marrow” (VEM). A much larger marrow island (petrosal non-endochondral marrow, PNEM) extended outside the otic capsule surrounding semicircular canal arms. PNEM was mainly connected to the dura, through bone channels similar to those of calvarial bone, and only a few channels were directed toward the canal periosteum. On the contrary, endochondral bone marrow was well connected to the labyrinth through vascular loops (directed to the spiral ligament for CAEM and to the bony labyrinth periosteum for VEM), and to dural sinuses. In addition, CAEM was also connected to the tensor tympani fossa of the middle ear and VEM to the endolymphatic sac. Endochondral marrow was made up of small lobules connected to each other and to other structures by channels lined by elongated macrophages, whereas PNEM displayed larger lobules connected by channels with a sparse macrophage population. Our data suggest that the rat inner ear is surrounded by bone marrow at the junctions with middle ear and brain, most likely with “customs” role, restricting pathogen spread; a second marrow network with different structural features is found within the endochondral bone layer of the otic capsule and may play different functional roles.

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Three-dimensional mouse cochlea imaging based on the modified Sca/eS using confocal microscopy

Cited by 5 publications

References 53 publications

Early-Onset Hearing Loss in Mouse Models of Alzheimer’s Disease and Increased DNA Damage in the Cochlea

Early-Onset Hearing Loss in Mouse Models of Alzheimer’s Disease and Increased DNA Damage in the Cochlea

A systematic review of the clinical evidence for an association between type I hypersensitivity and inner ear disorders

Temporal bone marrow of the rat and its connections to the inner ear

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