scholarly journals mTOR Signaling in the Inner Ear as Potential Target to Treat Hearing Loss

2021 ◽  
Vol 22 (12) ◽  
pp. 6368
Author(s):  
Maurizio Cortada ◽  
Soledad Levano ◽  
Daniel Bodmer
Keyword(s):  
Hearing Loss ◽  
Cell Survival ◽  
Inner Ear ◽  
Hearing Aids ◽  
Noise Exposure ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Signaling ◽  
Curative Therapy ◽  
Age Related ◽  
Survival Pathways

Hearing loss affects many people worldwide and occurs often as a result of age, ototoxic drugs and/or excessive noise exposure. With a growing number of elderly people, the number of people suffering from hearing loss will also increase in the future. Despite the high number of affected people, for most patients there is no curative therapy for hearing loss and hearing aids or cochlea implants remain the only option. Important treatment approaches for hearing loss include the development of regenerative therapies or the inhibition of cell death/promotion of cell survival pathways. The mammalian target of rapamycin (mTOR) pathway is a central regulator of cell growth, is involved in cell survival, and has been shown to be implicated in many age-related diseases. In the inner ear, mTOR signaling has also started to gain attention recently. In this review, we will emphasize recent discoveries of mTOR signaling in the inner ear and discuss implications for possible treatments for hearing restoration.

scholarly journals Noise Induced Hearing Loss: A Case Study from a Speech-Language Pathologist’s Perspective

2021 ◽  
Author(s):  
Alejandro Brice
Keyword(s):  
Hearing Loss ◽  
Inner Ear ◽  
Hearing Aids ◽  
Noise Exposure ◽  
Chronic Health Condition ◽  
Noise Induced Hearing Loss ◽  
Speech Language Pathologist ◽  
The Individual ◽  
The U.S

Hearing loss is very common in the United States and the most widespread disability in the U.S. Hearing loss is the third most chronic health condition in the U.S. Noise induced hearing loss (NIHL) results from damaging external noise. This injury leads to temporarily or permanently affecting sensitive inner ear structures (e.g., cochlea, organ of Corti, and hair cells). NIHL can result from a single high-level noise exposure or repeated exposures to excessively loud noises [i.e., typically 85 dBA or greater, (A weighted decibel)]. Damage to the inner ear can also result from aging (i.e., presbycusis). This case study documents the hearing loss of an otherwise healthy 21-year-old, male individual and his progressive moderate-to-severe sensorineural hearing loss over a period of 41 years. His history will be reported along with his perspective as a speech-language pathologist and speech scientist. The individual with hearing loss has adapted to wearing hearing aids over the last five years. Issues that have occurred affecting comprehension along with compensatory strategies that assisted listening and comprehension will be discussed.

scholarly journals IGF-1 Haploinsufficiency Causes Age-Related Chronic Cochlear Inflammation and Increases Noise-Induced Hearing Loss

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1686
Author(s):  
Adelaida M. Celaya ◽  
Lourdes Rodríguez-de la Rosa ◽  
Jose M. Bermúdez-Muñoz ◽  
José M. Zubeldia ◽  
Carlos Romá-Mateo ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Inflammatory Cytokines ◽  
Noise Exposure ◽  
Sensorineural Deafness ◽  
Serum Levels ◽  
Genetic Syndromes ◽  
Expression Ratio ◽  
Postnatal Maturation ◽  
Age Related ◽  
Underlying Mechanisms

Insulin-like growth factor 1 (IGF-1) deficiency is an ultrarare syndromic human sensorineural deafness. Accordingly, IGF-1 is essential for the postnatal maturation of the cochlea and the correct wiring of hearing in mice. Less severe decreases in human IGF-1 levels have been associated with other hearing loss rare genetic syndromes, as well as with age-related hearing loss (ARHL). However, the underlying mechanisms linking IGF-1 haploinsufficiency with auditory pathology and ARHL have not been studied. Igf1-heterozygous mice express less Igf1 transcription and have 40% lower IGF-1 serum levels than wild-type mice. Along with ageing, IGF-1 levels decreased concomitantly with the increased expression of inflammatory cytokines, Tgfb1 and Il1b, but there was no associated hearing loss. However, noise exposure of these mice caused increased injury to sensory hair cells and irreversible hearing loss. Concomitantly, there was a significant alteration in the expression ratio of pro- and anti-inflammatory cytokines in Igf1+/− mice. Unbalanced inflammation led to the activation of the stress kinase JNK and the failure to activate AKT. Our data show that IGF-1 haploinsufficiency causes a chronic subclinical proinflammatory age-associated state and, consequently, greater susceptibility to stressors. This work provides the molecular bases to further understand hearing disorders linked to IGF-1 deficiency.

scholarly journals Crosstalk of the Caspase Family and Mammalian Target of Rapamycin Signaling

2021 ◽  
Vol 22 (2) ◽  
pp. 817
Author(s):  
Junfang Yan ◽  
Yi Xie ◽  
Jing Si ◽  
Lu Gan ◽  
Hongyan Li ◽  
...  
Keyword(s):  
Cell Growth ◽  
Cell Survival ◽  
Cell Fate ◽  
Cellular Stress ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Signaling ◽  
Target Of Rapamycin ◽  
Dependent Manner ◽  
Caspase Family ◽  
Mediate Cell

Cell can integrate the caspase family and mammalian target of rapamycin (mTOR) signaling in response to cellular stress triggered by environment. It is necessary here to elucidate the direct response and interaction mechanism between the two signaling pathways in regulating cell survival and determining cell fate under cellular stress. Members of the caspase family are crucial regulators of inflammation, endoplasmic reticulum stress response and apoptosis. mTOR signaling is known to mediate cell growth, nutrition and metabolism. For instance, over-nutrition can cause the hyperactivation of mTOR signaling, which is associated with diabetes. Nutrition deprivation can inhibit mTOR signaling via SH3 domain-binding protein 4. It is striking that Ras GTPase-activating protein 1 is found to mediate cell survival in a caspase-dependent manner against increasing cellular stress, which describes a new model of apoptosis. The components of mTOR signaling-raptor can be cleaved by caspases to control cell growth. In addition, mTOR is identified to coordinate the defense process of the immune system by suppressing the vitality of caspase-1 or regulating other interferon regulatory factors. The present review discusses the roles of the caspase family or mTOR pathway against cellular stress and generalizes their interplay mechanism in cell fate determination.

scholarly journals Chronic Oral Selegiline Treatment Mitigates Age-Related Hearing Loss in BALB/c Mice

2021 ◽  
Vol 22 (6) ◽  
pp. 2853
Author(s):  
Judit Szepesy ◽  
Viktória Humli ◽  
János Farkas ◽  
Ildikó Miklya ◽  
Júlia Tímár ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hearing Aids ◽  
Dose Range ◽  
Auditory Brainstem ◽  
High Frequency Hearing Loss ◽  
Age Related ◽  
Hearing Function ◽  
Brainstem Response ◽  
Aging Societies ◽  
Age Related Hearing Loss

Age-related hearing loss (ARHL), a sensorineural hearing loss of multifactorial origin, increases its prevalence in aging societies. Besides hearing aids and cochlear implants, there is no FDA approved efficient pharmacotherapy to either cure or prevent ARHL. We hypothesized that selegiline, an antiparkinsonian drug, could be a promising candidate for the treatment due to its complex neuroprotective, antioxidant, antiapoptotic, and dopaminergic neurotransmission enhancing effects. We monitored by repeated Auditory Brainstem Response (ABR) measurements the effect of chronic per os selegiline administration on the hearing function in BALB/c and DBA/2J mice, which strains exhibit moderate and rapid progressive high frequency hearing loss, respectively. The treatments were started at 1 month of age and lasted until almost a year and 5 months of age, respectively. In BALB/c mice, 4 mg/kg selegiline significantly mitigated the progression of ARHL at higher frequencies. Used in a wide dose range (0.15–45 mg/kg), selegiline had no effect in DBA/2J mice. Our results suggest that selegiline can partially preserve the hearing in certain forms of ARHL by alleviating its development. It might also be otoprotective in other mammals or humans.

scholarly journals A Review on Recent Advancement on Age-Related Hearing Loss: The Applications of Nanotechnology, Drug Pharmacology, and Biotechnology

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1041
Author(s):  
Jacqueline Chester ◽  
Edan Johnston ◽  
Daniel Walker ◽  
Melissa Jones ◽  
Corina Mihaela Ionescu ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Bile Acid ◽  
Hearing Aids ◽  
Stria Vascularis ◽  
Cellular Damage ◽  
Relevant Evidence ◽  
Neuronal Signalling ◽  
Age Related ◽  
Recent Advancement ◽  
Age Related Hearing Loss

Aging is considered a contributing factor to many diseases such as cardiovascular disease, Alzheimer’s disease, and hearing loss. Age-related hearing loss, also termed presbycusis, is one of the most common sensory impairments worldwide, affecting one in five people over 50 years of age, and this prevalence is growing annually. Associations have emerged between presbycusis and detrimental health outcomes, including social isolation and mental health. It remains largely untreatable apart from hearing aids, and with no globally established prevention strategies in the clinical setting. Hence, this review aims to explore the pathophysiology of presbycusis and potential therapies, based on a recent advancement in bile acid-based bio-nanotechnologies. A comprehensive online search was carried out using the following keywords: presbycusis, drugs, hearing loss, bile acids, nanotechnology, and more than 150 publications were considered directly relevant. Evidence of the multifaceted oxidative stress and chronic inflammation involvement in cellular damage and apoptosis that is associated with a loss of hair cells, damaged and inflamed stria vascularis, and neuronal signalling loss and apoptosis continues to emerge. New robust and effective therapies require drug delivery deeper into the various layers of the cochlea. Bile acid-based nanotechnology has gained wide interest in its permeation-enhancing ability and potential for numerous applications in treating presbycusis.

Vztah mezi presbyakuzí a poruchou kognitivních funkcí ve stáří PDF uzamčeno English info

2021 ◽  
Vol 70 (4) ◽  
pp. 223-233
Author(s):  
Jakub Fuksa ◽  
Milan Profant ◽  
Martin Chovanec ◽  
Josef Syka
Keyword(s):  
Hearing Loss ◽  
Cognitive Impairment ◽  
Hearing Aids ◽  
Cognitive Functions ◽  
Auditory Information ◽  
Ageing Population ◽  
Published Evidence ◽  
Age Related ◽  
Keywords Dementia ◽  
Increased Risk

Age-related hearing loss, presbycusis, is one of the most frequent sensory impairments in the ageing population. It is associated with pathologies of both inner ear and the central parts of the auditory system. Intact cognitive functions are necessary for the proper processing of complex auditory information. Since the beginning of the 80s, there is an increasing amount of evidence linking presbycusis to cognitive impairment and increased risk of dementia. The exact cause, which connects these two pathologies, is still unknown, although there are several hypotheses with various levels of evidence available. This review aims to describe the role of cognitive functions in the auditory processing, to summarize published evidence for a relationship between the hearing loss and cognitive impairment with a possible mechanism, which would explain this link. In addition, we discuss specific features of cognitive assessment in a person with hearing loss and describe the effect of hearing loss treatment, e. g. with hearing aids, cochlear implant and cognitive-hearing training on cognitive functions. Keywords: dementia – hearing loss – presbycusis – cognitive decline

AGE-RELATED ISSUES OF THE QUALITY OF LIFE IN HEARING IMPAIRED PATIENTS

2021 ◽  
pp. 885-892
Author(s):  
Л. Е. Голованова ◽  
Е. А. Огородникова ◽  
Е. С. Лаптева ◽  
М. Ю. Бобошко
Keyword(s):  
Quality Of Life ◽  
Hearing Loss ◽  
Hearing Aids ◽  
Pure Tone Audiometry ◽  
Hearing Impaired ◽  
Hearing Disorders ◽  
Age Related ◽  
Sf 36 ◽  
Significant Difference

Целью исследования было изучение качества жизни лиц с нарушениями слуха в разных возрастных группах. Обследованы 100 пациентов, обратившихся в городской сурдологический центр для взрослых в связи с нарушением слуха: 50 человек - 34-59 лет, 50 - 60 лет и старше, из которых 32 человека были пожилого возраста (60-74 года)и 18 - старческого (75-86 лет). Степень тугоухости оценивали на основании результатов тональной пороговой аудиометрии. Для исследования качества жизни все пациенты заполняли общий опросник MOS SF-36, отражающий физический и психологический компоненты здоровья, а также специальный опросник HHIА(E)-S для лиц с нарушениями слуха. Установлено, что шкала HHIА(E)-S демонстрирует высокую корреляцию со степенью тугоухости у пациентов моложе 60 лет ( R =0,98; достоверность различий на уровне p <0,05), которая снижается у пациентов 60 лет и старше ( R =0,94; различия в оценках при разной степени тугоухости недостоверны). Значительные трудности в старшей возрастной группе могут быть связаны с тем, что людям пожилого и, особенно, старческого возраста сложно пользоваться слуховыми аппаратами (или они для них неэффективны) и оценивать свои затруднения по шкалам опросника. Целесообразно использовать шкалу HHIА(Е)-S в качестве скринингового инструмента для раннего выявления тугоухости, направления пациентов к сурдологу и своевременного слухопротезирования. The aim of the research was to study the quality of life in hearing impaired patients of different age. 100 patients referred to the city audiology centre because of their hearing disorders were examined: 50 patients from 34 to 59 years old and 50 patients from 60 years and older, from which 32 patients were of older age (60 to 74 years old) and 18 of oldest age (75 to 86 years old). A degree of hearing loss was assessed according to results of pure tone audiometry. To study the quality of life all patients filled in the questionnaire MOS SF-36, which evaluates physical and psychological components of health, and the questionnaire HHIA(E)-S, designed specifically for patients with hearing disorders. The HHIA(E)-S scale was found to show high correlation with hearing loss degree in patients younger than 60 years old ( R =0,98 with statistically significant difference, p <0,05), with decreasing correlation in patients from 60 years and older ( R =0,98; no significant difference while assessing various hearing loss degrees). Considerable difficulties in this age group may be explained by the fact, that older and especially oldest patients have a challenge with hearing aids usage (or they are of low efficiency for them) and with assessing theirs difficulties on the questionnaire scales. The HHIA(E)-S scale is useful as a screening tool for early detection of hearing loss, referral of patients to an audiologist and prompt hearing aid fitting.

scholarly journals Macroautophagy—a novel β-amyloid peptide-generating pathway activated in Alzheimer's disease

2005 ◽  
Vol 171 (1) ◽  
pp. 87-98 ◽  
Author(s):  
W. Haung Yu ◽  
Ana Maria Cuervo ◽  
Asok Kumar ◽  
Corrinne M. Peterhoff ◽  
Stephen D. Schmidt ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Survival ◽  
Mammalian Target Of Rapamycin ◽  
Amyloid Peptide ◽  
Survival Pathways ◽  
Secretase Activity ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Β Amyloid Peptide

Macroautophagy, which is a lysosomal pathway for the turnover of organelles and long-lived proteins, is a key determinant of cell survival and longevity. In this study, we show that neuronal macroautophagy is induced early in Alzheimer's disease (AD) and before β-amyloid (Aβ) deposits extracellularly in the presenilin (PS) 1/Aβ precursor protein (APP) mouse model of β-amyloidosis. Subsequently, autophagosomes and late autophagic vacuoles (AVs) accumulate markedly in dystrophic dendrites, implying an impaired maturation of AVs to lysosomes. Immunolabeling identifies AVs in the brain as a major reservoir of intracellular Aβ. Purified AVs contain APP and β-cleaved APP and are highly enriched in PS1, nicastrin, and PS-dependent γ-secretase activity. Inducing or inhibiting macroautophagy in neuronal and nonneuronal cells by modulating mammalian target of rapamycin kinase elicits parallel changes in AV proliferation and Aβ production. Our results, therefore, link β-amyloidogenic and cell survival pathways through macroautophagy, which is activated and is abnormal in AD.

scholarly journals Association of Age-Related Hearing Loss with Cognitive Decline

2020 ◽  
Vol 63 (4) ◽  
pp. 145-153
Author(s):  
Juyong Chung
Keyword(s):  
Hearing Loss ◽  
Cognitive Decline ◽  
Cochlear Implants ◽  
Hearing Aids ◽  
Microvascular Disease ◽  
Single Mechanism ◽  
Hearing Aid Use ◽  
Age Related ◽  
Age Related Hearing Loss

A number of studies have demonstrated a significant association between age-related hearing loss (ARHL) and cognitive decline. However their relationship is not clear. In this review, we focused on the etiological mechanisms between ARHL and cognitive decline to explain the nature of this relationship: 1) causal mechanisms (e.g., cognitive load hypothesis, cascade hypothesis); 2) common cause mechanisms (e.g., microvascular disease); 3) overdiagnosis or harbinger hypothesis. We conclude that no single mechanism is sufficient and hearing and cognition related to each other in several different ways. In addition, we reviewed the effectiveness of hearing intervention (e.g., hearing aids and cochlear implants) on cognition function, and the role of hearing aid use and cochlear implant depends on the relevant mechanism.

scholarly journals Shift of musical hallucinations to visual hallucinations after correction of the hearing deficit in a patient with Lewy body dementia: a case report

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Alexandre Montalvo ◽  
Eryco Azevedo ◽  
Alexandre de Mendonça
Keyword(s):  
Hearing Loss ◽  
Hearing Aids ◽  
Instrumental Music ◽  
Auditory Hallucination ◽  
Sensory Modality ◽  
Lewy Bodies ◽  
Lewy Body Dementia ◽  
Visual Hallucinations ◽  
Sensory Deficits ◽  
Age Related

Abstract Background Musical hallucinations are a particular type of auditory hallucination in which the patient perceives instrumental music, musical sounds, or songs. Musical hallucinations are associated with acquired hearing loss, particularly within the elderly. Under conditions of reduced auditory sensory input, perception-bearing circuits are disinhibited and perceptual traces released, implying an interaction between peripheral sensory deficits and central factors related to brain dysfunction. Case presentation A 71-year-old Caucasian man with hearing loss complained of memory difficulties and resting tremor of the right upper limb in the previous 2 years. He already had difficulties in instrumental activities of daily life. Neurological examination showed Parkinsonian signs and hypoacusia. Neuropsychological examination identified deficits in executive functions and memory tests. Brain computerized tomography and nuclear magnetic resonance scans showed mild cortical and subcortical atrophy. The clinical diagnosis of possible dementia with Lewy bodies was established. Five years later, the patient began complaining of musical hallucinations. There had been no previous change in medication. An otorhinolaryngologist diagnosed age-related hearing loss and prescribed bilateral hearing aids. After using the hearing aids, the patient did not hear the songs any longer, only some tinnitus, described as a whistle. However, at the same time, the patient started experiencing visual hallucinations he never had before. Discussion To our knowledge, the immediate shift of hallucinations from one sensory modality to another sensory modality when perception is improved has not been previously described. This report emphasizes the interaction between brain pathology and sensory deficits for the genesis of hallucinations, and reinforces the theory that attention and control networks must couple properly to the default mode network, as well as integrate and select adequately peripheral signals to the somatosensory cortices, in order to keep a clear state of mind. Conclusion The clinician should bear in mind and let the patient know that improving one sensory modality to ameliorate hallucinations may sometimes paradoxically lead to hallucinations in a different sensory modality.

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