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1.
J Neurol ; 271(6): 3527-3536, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38538775

RESUMO

BACKGROUND: Vestibular dysfunction is closely associated with the pathophysiology of Parkinson's disease (PD) accompanied by freezing of gait (FOG); however, evidence supporting this clinical association is lacking. Vestibular-evoked myogenic potentials (VEMPs) have been widely acknowledged as a crucial electrophysiological parameter in the clinical evaluation of vestibular function. OBJECTIVE: The present study investigated the possible correlation of FOG occurrence with VEMP observations in patients diagnosed with PD. METHODS: Altogether, 95 idiopathic PD patients were recruited into the present cross-sectional study. All patients underwent motor and non-motor assessments using serial scales. In addition, the electrophysiological vestibular evaluation was conducted, which included cervical (cVEMP) and ocular VEMP (oVEMP) assessments. Furthermore, the correlations of bilateral c/oVEMP absence with clinical phenotypes, especially FOG, among the PD patients were analyzed. RESULTS: Among the 95 patients with PD, 44 (46.3%) had bilateral oVEMP absence and 23 (24.2%) had bilateral cVEMP absence, respectively. The proportions of patients with bilateral oVEMP absence (77.8% vs 30.9%, p = 0.004) and bilateral cVEMP absence (44.4% vs 19.5%, p = 0.035) were higher in the patient group exhibiting FOG than in the group without FOG. Following the adjustment of confounding variables, bilateral oVEMP absence (OR = 8.544, p = 0.007), rather than bilateral cVEMP absence, was shown to independently predict FOG occurrence in patients with PD. CONCLUSION: The close correlation between bilateral oVEMP absence and FOG in PD patients sheds new light on the possible role of central vestibular/upper brainstem dysfunction in FOG development in patients with PD.


Assuntos
Transtornos Neurológicos da Marcha , Doença de Parkinson , Potenciais Evocados Miogênicos Vestibulares , Humanos , Doença de Parkinson/fisiopatologia , Doença de Parkinson/complicações , Feminino , Masculino , Idoso , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/fisiopatologia , Potenciais Evocados Miogênicos Vestibulares/fisiologia , Estudos Transversais , Pessoa de Meia-Idade , Doenças Vestibulares/fisiopatologia , Doenças Vestibulares/etiologia
2.
Neurobiol Aging ; 136: 111-124, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38342072

RESUMO

In mammals, thick axonal calibers wrapped with heavy myelin sheaths are prevalent in the auditory nervous system. These features are crucial for fast traveling of nerve impulses with minimal attenuation required for sound signal transmission. In particular, the long-range projections from the cochlear nucleus - the axons of globular bush cells (GBCs) - to the medial nucleus of the trapezoid body (MNTB) are tonotopically organized. However, it remains controversial in gerbils and mice whether structural and functional adaptations are present among the GBC axons targeting different MNTB frequency regions. By means of high-throughput volume electron microscopy, we compared the GBC axons in full-tonotopy-ranged MNTB slices from the C57BL/6 mice at different ages. Our quantification reveals distinct caliber diameter and myelin profile of the GBC axons with endings at lateral and medial MNTB, arguing for modulation of functionally heterogeneous axon subgroups. In addition, we reported axon-specific differences in axon caliber, node of Ranvier, and myelin sheath among juvenile, adult, and old mice, indicating the age-related changes of GBC axon morphology over time. These findings provide structural insight into the maturation and degeneration of GBC axons with frequency tuning across the lifespan of mice.


Assuntos
Vias Auditivas , Núcleo Coclear , Camundongos , Animais , Vias Auditivas/fisiologia , Microscopia Eletrônica de Volume , Camundongos Endogâmicos C57BL , Axônios/fisiologia , Núcleo Coclear/fisiologia , Bainha de Mielina , Mamíferos
3.
Orphanet J Rare Dis ; 17(1): 65, 2022 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-35189936

RESUMO

BACKGROUND: POU3F4 is the causative gene for X-linked deafness-2 (DFNX2), characterized by incomplete partition type III (IP-III) malformation of the inner ear. The purpose of this study was to investigate the clinical characteristics and molecular findings in IP-III patients by Sanger or nanopore single-molecule sequencing. METHODS: Diagnosis of IP-III was mainly based on clinical characteristics including radiological and audiological findings. Sanger sequencing of POU3F4 was carried out for these IP-III patients. For those patients with negative results for POU3F4 Sanger sequencing, nanopore long-read single-molecule sequencing was used to identify the possible pathogenic variants. Hearing intervention outcomes of hearing aids (HAs) fitting and cochlear implantation (CI) were also analyzed. Aided pure tone average (PTA) was further compared between two groups of patients according to their different locations of POU3F4 variants: in the exon region or in the upstream region. RESULTS: In total, 18 male patients from 14 unrelated families were diagnosed with IP-III. 10 variants were identified in POU3F4 by Sanger sequencing and 6 of these were reported for the first time (p.Gln181*, p.Val215Gly, p.Arg282Gln, p.Gln316*, c.903_912 delins TGCCA and p.Arg205del). Four different deletions that varied from 80 to 486 kb were identified 876-1503 kb upstream of POU3F4 by nanopore long-read single-molecule sequencing. De novo genetic mutations occurred in 21.4% (3/14) of patients with POU3F4 mutations. Among these 18 patients, 7 had bilateral HAs and 10 patients received unilateral CI. The mean aided PTA for HAs and CI users were 41.1 ± 5.18 and 40.3 ± 7.59 dB HL respectively. The mean PTAs for patients with the variants located in the exon and upstream regions were 39.6 ± 6.31 versus 43.0 ± 7.10 dB HL, which presented no significant difference (p = 0.342). CONCLUSIONS: Among 14 unrelated IP-III patients, 28.6% (4/14) had no definite mutation in exon region of POU3F4. However, possible pathogenic deletions were identified in upstream region of this gene. De novo genetic mutations occurred in 21.4% (3/14) of patients with POU3F4 mutation. There was no significant difference of hearing intervention outcomes between the IP-III patients with variants located in the exon region and in the upstream region.


Assuntos
Perda Auditiva Neurossensorial , Perda Auditiva , Sequenciamento por Nanoporos , Nanoporos , Perda Auditiva/genética , Perda Auditiva Neurossensorial/genética , Humanos , Masculino , Mutação/genética , Fatores do Domínio POU/genética
4.
iScience ; 24(11): 103285, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34765914

RESUMO

Auditory brainstem response (ABR) serves as an objective indication of auditory perception at a given sound level and is nowadays widely used in hearing function assessment. Despite efforts for automation over decades, ABR threshold determination by machine algorithms remains unreliable and thereby one still relies on visual identification by trained personnel. Here, we described a procedure for automatic threshold determination that can be used in both animal and human ABR tests. The method terminates level averaging of ABR recordings upon detection of time-locked waveform through cross-correlation analysis. The threshold level was then indicated by a dramatic increase in the sweep numbers required to produce "qualified" level averaging. A good match was obtained between the algorithm outcome and the human readouts. Moreover, the method varies the level averaging based on the cross-correlation, thereby adapting to the signal-to-noise ratio of sweep recordings. These features empower a robust and fully automated ABR test.

5.
Front Pediatr ; 9: 655625, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34055691

RESUMO

Objective: To compare the hearing screening results of two-step transient evoked otoacoustic emissions (TEOAE) and one-step automatic auditory brainstem response (AABR) in non-risk newborns, and to explore a more suitable hearing screening protocol for infants discharged within 48 h after birth in remote areas of China. Methods: To analyze the age effect on pass rate for hearing screening, 2005 newborns were divided into three groups according to screening time after birth: <24, 24-48, and 48-72 h. All subjects received TEOAE + AABR test as first hearing screen, and those who failed in any test were rescreened with TEOAE + AABR at 6 weeks after birth. The first screening results of AABR and TEOAE were compared among the three groups. The results of two-step TEOAE screening and one-step AABR screening were compared for newborns who were discharged within 48 h. The time spent on screening was recorded for TEOAE and AABR. Results: The pass rate of TEOAE and AABR increased significantly with the increase of first screening time (P < 0.05), and the false positive rate decreased significantly with the increase of first screening time (P < 0.05). The failure rate of first screening of AABR within 48 h was 7.31%, which was significantly lower than that of TEOAE (9.93%) (P < 0.05). The average time spent on AABR was 12.51 ± 6.36 min, which was significantly higher than that of TEOAE (4.05 ± 1.56 min, P < 0.05). The failure rate of TEOAE two-step screening was 1.59%, which was significantly lower than one-step AABR. Conclusions: Compared with TEOAE, AABR screening within 48 h after birth can reduce the failure rate and false positive rate of first screening. However, compared with TEOAE two-step screening, one-step AABR screening has higher referral rate for audiological diagnosis. In remote areas of China, especially in hospitals with high delivery rate, one-step AABR screening is not feasible, and two-step TEOAE screening protocol is still applicable to UNHS screening as more and more infants discharged within 48 h after birth.

6.
Otol Neurotol ; 39(3): e173-e180, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29342042

RESUMO

HYPOTHESIS: We investigated whether salicylate induces tinnitus through alteration of the expression levels of brain-derived neurotrophic factor (BDNF), proBDNF, tyrosine kinase receptor B (TrkB), cAMP-responsive element-binding protein (CREB), and phosphorylated CREB (p-CREB) in the auditory cortex (AC). BACKGROUND: Salicylate medication is frequently used for long-term treatment in clinical settings, but it may cause reversible tinnitus. Salicylate-induced tinnitus is associated with changes related to central auditory neuroplasticity. Our previous studies revealed enhanced neural activity and ultrastructural synaptic changes in the central auditory system after long-term salicylate administration. However, the underlying mechanisms remained unclear. METHODS: Salicylate-induced tinnitus-like behavior in rats was confirmed using gap prepulse inhibition of acoustic startle and prepulse inhibition testing, followed by comparison of the expression levels of BDNF, proBDNF, TrkB, CREB, and p-CREB. Synaptic ultrastructure was observed under a transmission electron microscope. RESULTS: BDNF and p-CREB were upregulated along with ultrastructural changes at the synapses in the AC of rats treated chronically with salicylate (p < 0.05, compared with control group). These changes returned to normal after 14 days of recovery (p > 0.05). CONCLUSION: Long-term administration of salicylate increased BDNF expression and CREB activation, upregulated synaptic efficacy, and changed synaptic ultrastructure in the AC. There may be a relationship between these factors and the mechanism of tinnitus.


Assuntos
Córtex Auditivo/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/efeitos dos fármacos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/efeitos dos fármacos , Salicilatos/toxicidade , Animais , Córtex Auditivo/metabolismo , Córtex Auditivo/patologia , Masculino , Fosforilação/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Sinapses/efeitos dos fármacos , Sinapses/patologia , Zumbido
7.
Exp Ther Med ; 11(5): 1661-1667, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27168786

RESUMO

Mucous cell metaplasia/hyperplasia in the middle ear epithelium is associated with the occurrence of otitis media with effusion during infections. However, the mechanism by which Notch signaling regulates cell fate in the middle ear epithelium is unclear. The aim of the present study was to elucidate this mechanism by investigating the localization of Notch receptors, such as Notch1 and Notch2, and Notch ligands, such as Jagged1, in the normal mouse middle ear epithelium (NMMEE) using immunofluorescence. Furthermore, the mRNA expression levels of Notch receptors and ligands were evaluated using reverse transcription polymerase chain reaction (PCR). The effects of the γ-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine tert-butyl ester (DAPT) on epithelial cell proliferation were determined using 5-ethynyl-2'-deoxyuridine (EdU) staining and immunofluorescence staining of the apoptosis marker caspase-3 and the epithelial proliferation marker pan-cytokeratine. In addition, the differentiation of the NMMEE cells was characterized by evaluating the mRNA expression levels of the mucous cell-associated genes Arg2, Muc2, Spdef, Spink4 and Tff1 using quantitative PCR. Notch1, Notch2 and Jagged1 were observed to be co-localized throughout the mouse middle ear epithelium. Furthermore, Notch1-4, Jagged1, Jagged2, Dll1 and Dll4 mRNAs were expressed in the NMMEE cells. The inhibition of Notch by DAPT resulted in fewer EdU-positive cells and the upregulation of the expression levels of various mucous cell-associated genes. The results indicate that DAPT suppresses the proliferation of NMMEE cells while promoting their differentiation into mucous cells. Therefore, DAPT may provide a specific therapeutic strategy for the reversal of multiple pathological processes that are associated with epithelium thickening in the middle ear.

8.
Artigo em Inglês | MEDLINE | ID: mdl-26682914

RESUMO

AIMS: This study aims to investigate the roles of the number of accelerations and rotation angle in the treatment of posterior semicircular canal benign paroxysmal positional vertigo (PC-BPPV). METHODS: We enrolled 344 patients with unilateral PC-BPPV. Of these, 167 patients in the simple-step maneuver (SSM) group were accelerated twice and rotated 120° per step, whereas 177 patients in the multi-step maneuver (MSM) group were accelerated 4 times and rotated 60° per step. Dix-Hallpike (DH) tests were performed to categorize the treatment outcome as follows: 'symptom free' if the result was negative, 'symptom persistent' if the result remained positive after performing the maneuver 3 times or 'canal conversion' if horizontal nystagmus was evoked. RESULTS: Of the patients in the SSM and MSM groups, 78.4 and 91.5% became symptom free, respectively, while canal conversion occurred in 13.8 and 5.1%, respectively (p = 0.003, χ(2) test). The success rate after performing the maneuver once was 57.1% in the MSM and 32.3% in the SSM symptom-free patients (p = 0.001, χ(2) test). One month after the treatment, 22.0 and 9.6% of the SSM and MSM patients had symptom relapse, respectively (p = 0.007, χ(2) test). CONCLUSIONS: More accelerations and a smaller rotation angle improved the effectiveness and efficiency of the repositioning maneuvers and reduced canal conversion.


Assuntos
Vertigem Posicional Paroxística Benigna/terapia , Modalidades de Fisioterapia , Aceleração , Vertigem Posicional Paroxística Benigna/diagnóstico , Vertigem Posicional Paroxística Benigna/fisiopatologia , Equipamentos e Provisões , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Posicionamento do Paciente , Estudos Prospectivos , Rotação , Canais Semicirculares/fisiopatologia , Método Simples-Cego , Resultado do Tratamento
9.
Mol Med Rep ; 10(1): 15-20, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24788407

RESUMO

Atonal homolog 1 (Atoh1) is a basic helix­loop­helix transcription factor that is essential for inner ear hair cell differentiation. Previous studies have reported that Atoh1 gene transfer induces the production of ectopic hair cell­like cells (EHCLCs). In the present study, the effect of different Atoh1 expression levels and the duration of EHCLC formation on the lesser epithelial ridge (LER) of cochleae was examined using a human adenovirus serotype 5 (Ad5) vector encoding atoh1 and the reporter gene EGFP. Different Ad5­EGFP­atoh1/Ad5­EGFP virus titers were added to cultured cochlear explants and EHCLCs were detected in the LER at various time points. The results demonstrated that GFP alone did not induce EHCLCs. By contrast, Atoh1 expression induced EHCLCs as early as 2.5­5 days following EGFP­atoh1 infection in the LER and depending upon the viral titer, the number of EHCLCs increased with time. Higher Ad5­EGFP­atoh1 titers induced enhanced Atoh1 expression, resulting in an increase in EHCLCs. Lower Ad5­EGFP­atoh1 titers required more time for EHCLC formation and very low titers of Ad5­EGFP­atoh1 induced only weak Atoh1 expression and did not trigger EHCLC formation. In conclusion, the present study utilized an appropriate Ad5­EGFP­atoh1 titer range to induce Atoh1 expression and the subsequent production of EHCLCs. The results revealed that the Atoh1 expression level defined the fate of LER cells as either EHCLCs or nonsensory epithelial cells. This evidence may provide an important guideline for future studies into gene therapy strategies for the treatment of deafness.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Cóclea/citologia , Células Epiteliais/metabolismo , Adenoviridae/genética , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Células Epiteliais/citologia , Genes Reporter , Vetores Genéticos/metabolismo , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/genética
10.
Artigo em Chinês | MEDLINE | ID: mdl-22509692

RESUMO

OBJECTIVE: To evaluate the therapeutic results of endoscopic orbital decompression for thyroid-associated ophthalmopathy. METHOD: The records of nine patients (twelve orbits) received endoscopic orbital decompression for thyroid-associated ophthalmopathy were analyzed for changes in visual acuity, intraocular pressure, proptosis, corneal ulceration and movement. The follow-ups ranged from two months to thirty-six months. RESULT: Twelve orbits (100%) had improvement in visual acuity (range 0.1-0.7). Ten orbits (83.3%) decreased in intraocular pressure (range 0.2-21.4 mm Hg). Eight orbits (66.70%) decreased in proptosis (one-five mm). The orbit with corneal ulcer was healed after decompression. Diplopia was cured in one of four patients. CONCLUSION: Endoscopic orbital decompression is a safe and effective procedure for the treatment of thyroid-associated ophthalmopathy.


Assuntos
Descompressão Cirúrgica/métodos , Oftalmopatia de Graves/cirurgia , Órbita/cirurgia , Adulto , Endoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
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