Expressão de proteínas ligantes de cálcio e receptores de melatonina em centros encefálicos da via auditiva no envelhecimento
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2019-05-06
Autores
Santos, Graziela Ligia da Silva [UNESP]
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Universidade Estadual Paulista (Unesp)
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Introdução: Durante o envelhecimento, em mamíferos, é comum o desenvolvimento da presbiacusia, caracterizada por perda de células ciliadas na cóclea associada a alterações nas funções neuronais dos núcleos do sistema auditivo central (SAC) que acarretam prejuízos auditivos. Dentre as alterações neuronais comuns no envelhecimento estão mudanças na expressão neuronal das proteínas ligantes de cálcio (CaBPs), fundamentais para o processamento nas estações da via auditiva, que podem compor assim o mecanismo da presbiacusia. Dentre as possíveis formas de tratamento e/ou prevenção da presbiacusia está a suplementação com substâncias antioxidantes e/ou neuroprotetoras que possam retardar a perda neuronal e/ou alterações funcionais dos neurônios. Dentre estas, o hormônio melatonina, tem demonstrado importante ação antioxidante e otoprotetora que podem ocorrer independente ou dependente dos receptores de melatonina MT1 e MT2. No entanto, não está claro, se nas estações do SAC encontram-se expressos tais receptores e se essa expressão poderia variar no envelhecimento. Considerando que as CaBPs estão alteradas em idosos, propõe-se verificar se estas alterações cursam com possíveis alterações na expressão dos receptores de melatonina no envelhecimento. Tal informação contribuirá para o entendimento dos mecanismos envolvidos na presbiacusia e para investigações sobre possíveis terapias otoprotetoras no envelhecimento. Objetivos: Avaliar a expressão das CaBPs e dos receptores de melatonina MT1 e MT2 em neurônios das estações sinápticas que compõem o SAC em ratos jovens e idosos. Comparar a morfologia dos neurônios imunorreativos as CaBPs entre ratos jovens e idosos. Materiais e Métodos: Cortes encefálicos de ratos jovens e idosos foram processados utilizando a técnica de imuno-histoquímica para identificar as proteínas parvalbumina (PV), calbindina (CB), calretinina (CR) e os receptores MT1 e MT2. Resultados: A densidade de células imunorreativas à PV (PV-ir) foi menor e o volume dos neurônios PV-ir no colículo inferior foi maior no grupo idoso. O número células CB- ir e CR-ir no complexo olivar superior também foi menor no grupo idoso quando comparado ao grupo jovem. No núcleo coclear, o número células CR-ir foi menor no grupo idoso quando comparado ao grupo jovem. No corpo geniculado medial não houve diferença na densidade de células e foi observado diminuição do volume dos neurônios CB-ir no grupo idoso. Houve aumento da expressão de MT1 no núcleo coclear, complexo olivar superior e colículo inferior de ratos idosos. A presença do MT1 foi verificada no corpo geniculado medial apenas no grupo idoso. Foi observado a presença do receptor MT2 na região do núcleo coclear, complexo olivar superior, colículo inferior e corpo geniculado medial apenas no grupo idoso. Discussão: A menor expressão de CaBPs e a alteração morfológica em neurônios CB-ir e PV-ir em núcleos da via auditiva central em ratos idosos indica que estes núcleos sofrem ação do envelhecimento. Já o aumento na expressão do receptor MT1 e a presença do receptor MT2 com o envelhecimento sugere que esta molécula tenha uma importante ação neuroprotetora nos núcleos da via auditiva. Conclusão: As CaBPs apresentaram menor expressão nos núcleos do SAC no grupo idoso. Os receptores de melatonina MT1 e MT2 apresentaram maior expressão nos núcleos do SAC no grupo idoso. O grupo idoso apresentou ainda maior volume dos neurônios PV-ir no colículo inferior e menor volume dos neurônios CB-ir no corpo geniculado medial.
During aging, in mammals, it is common the development of presbycusis, characterized by loss of cells in the cochlea associated with changes in the neuronal functions of the nuclei of the central auditory system (SAC) that cause auditory impairment. Among the common neuronal changes in aging are changes in the neuronal expression calcium-binding proteins (CaBPs), which are essential for processing in the auditory pathway stations, which can thus constitute the mechanism of presbycusis. Among the possible forms of treatment and/ or prevention of presbyacusis is the supplementation with antioxidant and/ or neuroprotective substances that may delay the neuronal loss and/ or functional alterations of the neurons. Among these, the hormone melatonin, has demonstrated important antioxidant and otoprotective action that can occur independent or dependent on the melatonin receptor MT1 and MT2. However, it is unclear whether SAC stations express suche receptors and whether such expression could vary in aging. Considerering that the CaBPs are altered in the elderly, it is proposed to verify if these altererations occur with possible alterations in the expression of the melatonin receptors in aging. Such information will contribute to understanding the mechanisms involved in presbycusis and to investigating possible otoprotective therapies in aging. Objective: To evaluate the expression of CaBPs and melatonin MT1 and MT2 receptors in synaptic stations neurons that compose SAC in young and elderly rats. To compare the morphology of immunoreactive neurons to CaBPs between young and elderly rats. Methods: Enceplhalic cords from young and elderly rats were processed using immunohistochemistry technique to indentify the proteins of parvalbumin (PV), calbindin (CB), calretinin (CR) and the MT1 and MT2 receptors. Quantification of the number of CaBPs positive cells will be performed by stereology and receptor expression will be assessed by optical density. Results: The density of PV immunoreactive cells (PV-ir) was lower and the PV-IR neuron volume in the inferior colliculus was higher in the elderly group. The number of CB-IR and CR-IR cells in the superior olivary complex was also lower in the elderly group when compared to the young group. In the cochlear nucleus, the numbers of CR-IR cells was lower in the elderly group when compared to the young group. In the medial geniculate body there was no difference in cell density and aa decrease in the volume of CB-IR neurons was observed in the elderly group. There was an increase in MT1 expression in the cochlear nucleus, superior olivary complex and inferior colliculus of elderly rats. The presence of MT1 was verified in the medial geniculate body only in the elderly group. The presence of the MT2 receptor was observed in the cochlear nucleus region, superior olivary complex, inferior colliculus and medial geniculate body only in the elderly group. Discussion: The lower expression of CaBPs and the morphological alteration in CB-IR and PV-IR neurons in central auditory pathways in elderly rats indicates that these nuclei undergo aging. Already the increase in MT1 receptor expression and the presence of the MT2 receptor with aging suggests that this molecule has an important neuroprotective action in the nuclei of the auditory pathway. Conclusion: The CaBPs presented lower expression in the nuclei of the SAC in the elderly group. The MT1 and MT2 melatonin receptors presented greater expression in the SAC nuclei in the elderly group. The older group presented an even higher volume of the PV-IR neurons of the inferior colliculus and lower volume of the CB-IR in the medial geniculate body.
During aging, in mammals, it is common the development of presbycusis, characterized by loss of cells in the cochlea associated with changes in the neuronal functions of the nuclei of the central auditory system (SAC) that cause auditory impairment. Among the common neuronal changes in aging are changes in the neuronal expression calcium-binding proteins (CaBPs), which are essential for processing in the auditory pathway stations, which can thus constitute the mechanism of presbycusis. Among the possible forms of treatment and/ or prevention of presbyacusis is the supplementation with antioxidant and/ or neuroprotective substances that may delay the neuronal loss and/ or functional alterations of the neurons. Among these, the hormone melatonin, has demonstrated important antioxidant and otoprotective action that can occur independent or dependent on the melatonin receptor MT1 and MT2. However, it is unclear whether SAC stations express suche receptors and whether such expression could vary in aging. Considerering that the CaBPs are altered in the elderly, it is proposed to verify if these altererations occur with possible alterations in the expression of the melatonin receptors in aging. Such information will contribute to understanding the mechanisms involved in presbycusis and to investigating possible otoprotective therapies in aging. Objective: To evaluate the expression of CaBPs and melatonin MT1 and MT2 receptors in synaptic stations neurons that compose SAC in young and elderly rats. To compare the morphology of immunoreactive neurons to CaBPs between young and elderly rats. Methods: Enceplhalic cords from young and elderly rats were processed using immunohistochemistry technique to indentify the proteins of parvalbumin (PV), calbindin (CB), calretinin (CR) and the MT1 and MT2 receptors. Quantification of the number of CaBPs positive cells will be performed by stereology and receptor expression will be assessed by optical density. Results: The density of PV immunoreactive cells (PV-ir) was lower and the PV-IR neuron volume in the inferior colliculus was higher in the elderly group. The number of CB-IR and CR-IR cells in the superior olivary complex was also lower in the elderly group when compared to the young group. In the cochlear nucleus, the numbers of CR-IR cells was lower in the elderly group when compared to the young group. In the medial geniculate body there was no difference in cell density and aa decrease in the volume of CB-IR neurons was observed in the elderly group. There was an increase in MT1 expression in the cochlear nucleus, superior olivary complex and inferior colliculus of elderly rats. The presence of MT1 was verified in the medial geniculate body only in the elderly group. The presence of the MT2 receptor was observed in the cochlear nucleus region, superior olivary complex, inferior colliculus and medial geniculate body only in the elderly group. Discussion: The lower expression of CaBPs and the morphological alteration in CB-IR and PV-IR neurons in central auditory pathways in elderly rats indicates that these nuclei undergo aging. Already the increase in MT1 receptor expression and the presence of the MT2 receptor with aging suggests that this molecule has an important neuroprotective action in the nuclei of the auditory pathway. Conclusion: The CaBPs presented lower expression in the nuclei of the SAC in the elderly group. The MT1 and MT2 melatonin receptors presented greater expression in the SAC nuclei in the elderly group. The older group presented an even higher volume of the PV-IR neurons of the inferior colliculus and lower volume of the CB-IR in the medial geniculate body.
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Palavras-chave
Envelhecimento, Sistema auditivo, CaBPs, Melatonina, Presbiacusia, Elderly, Auditory system, Melatonin, Presbyacusis