in-vivo-chronic-two-photon-imaging-microglia-mouse

<i>In Vivo</i> Chronic Two-Photon Imaging of Microglia in the Mouse Hippocampus

Microglia, the only immune cells resident in the brain, actively participate in neural circuit maintenance by modifying synapses and neuronal ...

The University of Tokyo

the university of tokyo

An 18-year-old patient presented with a major complaint of a mass in the right side of the neck. At the previous clinic, the patient underwent an open biopsy because the mass could not be diagnosed by fine needle aspiration. The patient was introduced to our institution after mass was diagnosed as ganglioneuroma by open biopsy. In our outpatient clinic, magnetic resonance imaging (MRI) and computed tomography (CT) were performed. Gradual growth of the mass was accompanied by sleep apnea syndrome. Ultimately, the patient was only able to sleep with nasal continuous positive airway pressure. Pathological examination confirmed the ganglioneuroma. MRI revealed expansion of the ganglioneuroma from the nasopharynx to the right upper mediastinum, occupying the surroundings of the contralateral carotid artery via the retropharyngeal space. CT revealed a tumor mass of 160mm×60mm×190mm in size. The mass was surgically resected without any postoperative neurological disorder including Horner syndrome. The clinical course was successful without recurrence. This is the first report of a successful treatment of a large ganglineuroma that had continuously expanded to the contralateral neck via the retropharyngeal space. 

Surgical management of a giant cervical ganglioneuroma.

Interleukin (IL)-33 is a novel member of the IL-1 cytokine family and a ligand for the orphan IL-1 family receptor ST2. IL-33 induces T helper 2-type inflammatory responses and is considered to play a crucial role in allergic inflammatory reactions such as asthma and atopic dermatitis. However, the role of IL-33 and its receptor ST2 in chronic rhinosinusitis remains unclear.

Expression of IL-33 and its receptor ST2 in chronic rhinosinusitis with nasal polyps.

Recurrent meningitis resulting from a partial defect of the stapedial footplate is most frequently treated by complete obliteration of the inner ear. Herein, we report the use of a partial obliteration technique in which the fistula is plugged with a shaped incus.

Novel repair of stapedial footplate defect associated with recurrent meningitis.

Hearing loss is the most frequent sensory disorder in humans. Auditory hair cells (HCs) are postmitotic at late-embryonic differentiation and postnatal stages, and their damage is the major cause of hearing loss. There is no measurable HC regeneration in the mammalian cochlea, and the maintenance of cell function is crucial for preservation of hearing. Here we generated mice deficient in autophagy-related 5 (Atg5), a gene essential for autophagy, in the HCs to investigate the effect of basal autophagy on hearing acuity. Deletion of Atg5 resulted in HC degeneration and profound congenital hearing loss. In autophagy-deficient HCs, polyubiquitinated proteins and p62/SQSTM1, an autophagy substrate, accumulated as inclusion bodies during the first postnatal week, and these aggregates increased in number. These findings revealed that basal autophagy has an important role in maintenance of HC morphology and hearing acuity.

Autophagy is essential for hearing in mice.

The highly organized spatial arrangement of sensory hair cells in the organ of Corti is essential for inner ear function. Here, we report a new analytical pipeline, based on optical clearing of tissue, for the construction of a single-cell resolution map of the organ of Corti. A sorbitol-based optical clearing method enabled imaging of the entire cochlea at subcellular resolution. High-fidelity detection and analysis of all hair cell positions along the entire longitudinal axis of the organ of Corti were performed automatically by machine learning-based pattern recognition. Application of this method to samples from young, adult, and noise-exposed mice extracted essential information regarding cellular pathology, including longitudinal and radial spatial characteristics of cell loss, implying that multiple mechanisms underlie clustered cell loss. Our method of cellular mapping is effective for system-level phenotyping of the organ of Corti under both physiological and pathological conditions.

Cellular cartography of the organ of Corti based on optical tissue clearing and machine learning.

Lysosome-associated membrane protein 5 (LAMP5) is a mammalian ortholog of the Caenorhabditis elegans protein, UNC-46, which functions as a sorting factor to localize the vesicular GABA transporter UNC-47 to synaptic vesicles. In the mouse forebrain, LAMP5 is expressed in a subpopulation of GABAergic neurons in the olfactory bulb and the striato-nigral system, where it is required for fine-tuning of GABAergic synaptic transmission. Here we focus on the prominent expression of LAMP5 in the brainstem and spinal cord and suggest a role for LAMP5 in these brain regions. LAMP5 was highly expressed in several brainstem nuclei involved with auditory processing including the cochlear nuclei, the superior olivary complex, nuclei of the lateral lemniscus and grey matter in the spinal cord. It was localized exclusively in inhibitory synaptic terminals, as has been reported in the forebrain. In the absence of LAMP5, localization of the vesicular inhibitory amino acid transporter (VIAAT) was unaltered in the lateral superior olive and the ventral cochlear nuclei, arguing against a conserved role for LAMP5 in trafficking VIAAT. Lamp5 knockout mice showed no overt behavioral abnormality but an increased startle response to auditory and tactile stimuli. In addition, LAMP5 deficiency led to a larger intensity-dependent increase of wave I, II and V peak amplitude of auditory brainstem response. Our results indicate that LAMP5 plays a pivotal role in sensorimotor processing in the brainstem and spinal cord.

LAMP5 in presynaptic inhibitory terminals in the hindbrain and spinal cord: a role in startle response and auditory processing.

Olfactory dysfunction is one of the most frequent and specific symptoms of coronavirus disease 2019 (COVID-19). Information on the damage and repair of the neuroepithelium and its impact on olfactory function after COVID-19 is still incomplete. While severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes the ongoing worldwide outbreak of COVID-19, little is known about the changes triggered by SARS-CoV-2 in the olfactory epithelium (OE) at the cellular level. Here, we report profiles of the OE after SARS-CoV-2 infection in golden Syrian hamsters, which is a reliable animal model of COVID-19. We observed severe damage in the OE as early as 3 days postinoculation and regionally specific damage and regeneration of the OE within the nasal cavity; the nasal septal region demonstrated the fastest recovery compared to other regions in the nasal turbinates. These findings suggest that anosmia related to SARS-CoV-2 infection may be fully reversible.

Regeneration Profiles of Olfactory Epithelium after SARS-CoV-2 Infection in Golden Syrian Hamsters.

The impact of SARS-CoV-2 on the olfactory pathway was studied over several time points using Syrian golden hamsters. We found an incomplete recovery of the olfactory sensory neurons, prolonged activation of glial cells in the olfactory bulb, and a decrease in the density of dendritic spines within the hippocampus. These data may be useful for elucidating the mechanism underlying long-lasting olfactory dysfunction and cognitive impairment as a post-acute COVID-19 syndrome.

Article	Year
Surgical management of a giant cervical ganglioneuroma. Auris, nasus, larynx\| PubMed ID: 23433475	2013
Expression of IL-33 and its receptor ST2 in chronic rhinosinusitis with nasal polyps. The Laryngoscope\| PubMed ID: 24122812	2014
Novel repair of stapedial footplate defect associated with recurrent meningitis. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology\| PubMed ID: 25141185	2014
Autophagy is essential for hearing in mice. Cell death & disease\| PubMed ID: 28492547	2017
Cellular cartography of the organ of Corti based on optical tissue clearing and machine learning. eLife\| PubMed ID: 30657453	2019
LAMP5 in presynaptic inhibitory terminals in the hindbrain and spinal cord: a role in startle response and auditory processing. Molecular brain\| PubMed ID: 30867010	2019
Regeneration Profiles of Olfactory Epithelium after SARS-CoV-2 Infection in Golden Syrian Hamsters. ACS chemical neuroscience\| PubMed ID: 33522795	2021
Prolonged and extended impacts of SARS-CoV-2 on the olfactory neurocircuit. Scientific reports\| PubMed ID: 35388072	2022

Shinji Urata

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