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1.
Hear Res ; 452: 109106, 2024 10.
Artigo em Inglês | MEDLINE | ID: mdl-39181061

RESUMO

Several studies suggest that hearing loss results in changes in the balance between inhibition and excitation in the inferior colliculus (IC). The IC is an integral nucleus within the auditory brainstem. The majority of ascending pathways from the lateral lemniscus (LL), superior olivary complex (SOC), and cochlear nucleus (CN) synapse in the IC before projecting to the thalamus and cortex. Many of these ascending projections provide inhibitory innervation to neurons within the IC. However, the nature and the distribution of this inhibitory input have only been partially elucidated in the rat. The inhibitory neurotransmitter, gamma aminobutyric acid (GABA), from the ventral nucleus of the lateral lemniscus (VNLL), provides the primary inhibitory input to the IC of the rat with GABA from other lemniscal and SOC nuclei providing lesser, but prominent innervation. There is evidence that hearing related conditions can result in dysfunction of IC neurons. These changes may be mediated in part by changes in GABA inputs to IC neurons. We have previously used gene micro-arrays in a study of deafness-related changes in gene expression in the IC and found significant changes in GAD as well as the GABA transporters and GABA receptors (Holt 2005). This is consistent with reports of age and trauma related changes in GABA (Bledsoe et al., 1995; Mossop et al., 2000; Salvi et al., 2000). Ototoxic lesions of the cochlea produced a permanent threshold shift. The number, intensity, and density of GABA positive axon terminals in the IC were compared in normal hearing and deafened rats. While the number of GABA immunolabeled puncta was only minimally different between groups, the intensity of labeling was significantly reduced. The ultrastructural localization and distribution of labeling was also examined. In deafened animals, the number of immuno gold particles was reduced by 78 % in axodendritic and 82 % in axosomatic GABAergic puncta. The affected puncta were primarily associated with small IC neurons. These results suggest that reduced inhibition to IC neurons contribute to the increased neuronal excitability observed in the IC following noise or drug induced hearing loss. Whether these deafness diminished inhibitory inputs originate from intrinsic or extrinsic CNIC sources awaits further study.


Assuntos
Colículos Inferiores , Ratos Sprague-Dawley , Ácido gama-Aminobutírico , Animais , Colículos Inferiores/metabolismo , Colículos Inferiores/patologia , Ácido gama-Aminobutírico/metabolismo , Perda Auditiva Provocada por Ruído/metabolismo , Perda Auditiva Provocada por Ruído/fisiopatologia , Perda Auditiva Provocada por Ruído/patologia , Ototoxicidade/metabolismo , Ototoxicidade/etiologia , Masculino , Vias Auditivas/metabolismo , Vias Auditivas/patologia , Vias Auditivas/fisiopatologia , Modelos Animais de Doenças , Imuno-Histoquímica , Ratos , Glutamato Descarboxilase/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Inibição Neural
2.
Rev. otorrinolaringol. cir. cabeza cuello ; 82(2): 179-183, jun. 2022. ilus
Artigo em Espanhol | LILACS | ID: biblio-1389852

RESUMO

Resumen La patología del sistema nervioso central, habitualmente, no provoca síntomas auditivos unilaterales, ya que la vía auditiva central está formada por una red de conexiones cruzadas entre los diferentes núcleos que la forman. Además, hay que considerar que una lesión pequeña puede extenderse a más de una estructura provocando varios déficits neurológicos debido a la proximidad de los tractos y núcleos nerviosos. Las lesiones unilaterales circunscritas en el colículo inferior son infrecuentes. No obstante, se han descrito casos en los que lesiones unilaterales de diversas etiologías en esta localización causaban síntomas auditivos. Ya que la vía auditiva central es cruzada, síntomas auditivos detectados con más frecuencia afectaban concretamente a la capacidad de localización del sonido o la comprensión verbal. Presentamos el caso de un hombre de 44 años con acúfeno unilateral derecho de larga evolución, sin otra clínica asociada quien fue diagnosticado de un tumor en el colículo inferior derecho mediante resonancia magnética cerebral. Se exponen los hallazgos clínicos y radiológicos del caso.


Abstract Central nervous system diseases usually do not cause auditory symptoms because the central auditory pathway consists on a network of crossed connections between the different nuclei that form it. In addition, we must consider that a small lesion might extend to more than one structure producing many neurologic symptoms due to the proximity of tracts and nuclei in the midbrain. Unilateral circumscribed lesions at inferior colliculus are rare. Nevertheless, lesions at this location causing auditory symptoms have been described. Because of the crossed central auditory pathway, the most commonly detected auditory symptoms specifically affected the ability to locate sound or verbal comprehension. We present the case of a 44-year-old man with a long-term monoaural right-sided tinnitus without other complaints who was diagnosed of a tumour at right inferior colliculus by neuroimaging. Clinical and radiological findings of this case are discussed.


Assuntos
Humanos , Masculino , Adulto , Zumbido/complicações , Colículos Inferiores/patologia , Espectroscopia de Ressonância Magnética , Doenças do Sistema Nervoso Central , Neoplasias
3.
J Neurotrauma ; 38(23): 3248-3259, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34605670

RESUMO

In the present study, we have evaluated the blast-induced auditory neurodegeneration in chinchilla by correlating the histomorphometric changes with diffusion tensor imaging. The chinchillas were exposed to single unilateral blast-overpressure (BOP) at ∼172dB peak sound pressure level (SPL) and the pathological changes were compared at 1 week and 1 month after BOP. The functional integrity of the auditory system was assessed by auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE). The axonal integrity was assessed using diffusion tensor imaging at regions of interests (ROIs) of the central auditory neuraxis (CAN) including the cochlear nucleus (CN), inferior colliculus (IC), and auditory cortex (AC). Post-BOP, cyto-architecture metrics such as viable cells, degenerating neurons, and apoptotic cells were quantified at the CAN ROIs using light microscopic studies using cresyl fast violet, hematoxylin and eosin, and modified Crossmon's trichrome stains. We observed mean ABR threshold shifts of 30- and 10-dB SPL at 1 week and 1 month after BOP, respectively. A similar pattern was observed in DPAOE amplitudes shift. In the CAN ROIs, diffusion tensor imaging studies showed a decreased axial diffusivity in CN 1 month after BOP and a decreased mean diffusivity and radial diffusivity at 1 week after BOP. However, morphometric measures such as decreased viable cells and increased degenerating neurons and apoptotic cells were observed at CN, IC, and AC. Specifically, increased degenerating neurons and reduced viable cells were high on the ipsilateral side when compared with the contralateral side. These results indicate that a single blast significantly damages structural and functional integrity at all levels of CAN ROIs.


Assuntos
Córtex Auditivo/patologia , Traumatismos por Explosões/patologia , Núcleo Coclear/patologia , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Perda Auditiva Provocada por Ruído/patologia , Colículos Inferiores/patologia , Doenças Neurodegenerativas/patologia , Animais , Córtex Auditivo/diagnóstico por imagem , Traumatismos por Explosões/complicações , Traumatismos por Explosões/diagnóstico por imagem , Chinchila , Núcleo Coclear/diagnóstico por imagem , Imagem de Tensor de Difusão , Modelos Animais de Doenças , Perda Auditiva Provocada por Ruído/diagnóstico por imagem , Colículos Inferiores/diagnóstico por imagem , Doenças Neurodegenerativas/diagnóstico por imagem
4.
Neurobiol Aging ; 105: 1-15, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34004491

RESUMO

The age-related loss of GABA in the inferior colliculus (IC) likely plays a role in the development of age-related hearing loss. Perineuronal nets (PNs), specialized aggregates of extracellular matrix, increase with age in the IC. PNs, associated with GABAergic neurotransmission, can stabilize synapses and inhibit structural plasticity. We sought to determine whether PN expression increased on GABAergic and non-GABAergic IC cells that project to the medial geniculate body (MG). We used retrograde tract-tracing in combination with immunohistochemistry for glutamic acid decarboxylase and Wisteria floribunda agglutinin across three age groups of Fischer Brown Norway rats. Results demonstrate that PNs increase with age on lemniscal and non-lemniscal IC-MG cells, however two key differences exist. First, PNs increased on non-lemniscal IC-MG cells during middle-age, but not until old age on lemniscal IC-MG cells. Second, increases of PNs on lemniscal IC-MG cells occurred on non-GABAergic cells rather than on GABAergic cells. These results suggest that synaptic stabilization and reduced plasticity likely occur at different ages on a subset of the IC-MG pathway.


Assuntos
Envelhecimento/patologia , Neurônios GABAérgicos/patologia , Neurônios GABAérgicos/fisiologia , Colículos Inferiores/citologia , Colículos Inferiores/patologia , Rede Nervosa/patologia , Rede Nervosa/fisiopatologia , Tálamo/citologia , Tálamo/patologia , Animais , Vias Auditivas/fisiologia , Corpos Geniculados/citologia , Corpos Geniculados/patologia , Glutamato Descarboxilase/metabolismo , Perda Auditiva/etiologia , Perda Auditiva/patologia , Masculino , Lectinas de Plantas , Ratos , Receptores de N-Acetilglucosamina
5.
J Comp Neurol ; 529(5): 957-968, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32681585

RESUMO

Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a neurodegenerative disease due to mutations in TUBB4A. Patients suffer from extrapyramidal movements, spasticity, ataxia, and cognitive deficits. Magnetic resonance imaging features are hypomyelination and atrophy of the striatum and cerebellum. A correlation between the mutations and their cellular, tissue and organic effects is largely missing. The effects of these mutations on sensory functions have not been described so far. We have previously reported a rat carrying a TUBB4A (A302T) mutation and sharing most of the clinical and radiological signs with H-ABC patients. Here, for the first time, we did a comparative study of the hearing function in an H-ABC patient and in this mutant model. By analyzing hearing function, we found that there are no significant differences in the auditory brainstem response (ABR) thresholds between mutant rats and WT controls. Nevertheless, ABRs show longer latencies in central waves (II-IV) that in some cases disappear when compared to WT. The patient also shows abnormal AEPs presenting only Waves I and II. Distortion product of otoacoustic emissions and immunohistochemistry in the rat show that the peripheral hearing function and morphology of the organ of Corti are normal. We conclude that the tubulin mutation severely impairs the central hearing pathway most probably by progressive central white matter degeneration. Hearing function might be affected in a significant fraction of patients with H-ABC; therefore, screening for auditory function should be done on patients with tubulinopathies to evaluate hearing support therapies.


Assuntos
Deficiências do Desenvolvimento/genética , Distúrbios Distônicos/genética , Perda Auditiva Neurossensorial/genética , Tubulina (Proteína)/deficiência , Substituição de Aminoácidos , Animais , Percepção Auditiva , Pré-Escolar , Núcleo Coclear/patologia , Doenças Desmielinizantes/genética , Modelos Animais de Doenças , Orelha Interna/fisiopatologia , Potenciais Evocados Auditivos , Feminino , Perda Auditiva Neurossensorial/fisiopatologia , Humanos , Colículos Inferiores/patologia , Masculino , Mutação de Sentido Incorreto , Bainha de Mielina/patologia , Mutação Puntual , Ratos , Ratos Mutantes , Ratos Sprague-Dawley , Tubulina (Proteína)/genética
6.
Int J Mol Sci ; 21(22)2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33233709

RESUMO

Noise-induced hearing loss (NIHL) can lead to secondary changes that induce neural plasticity in the central auditory pathway. These changes include decreases in the number of synapses, the degeneration of auditory nerve fibers, and reorganization of the cochlear nucleus (CN) and inferior colliculus (IC) in the brain. This study investigated the role of microRNAs (miRNAs) in the neural plasticity of the central auditory pathway after acute NIHL. Male Sprague-Dawley rats were exposed to white band noise at 115 dB for 2 h, and the auditory brainstem response (ABR) and morphology of the organ of Corti were evaluated on days 1 and 3. Following noise exposure, the ABR threshold shift was significantly smaller in the day 3 group, while wave II amplitudes were significantly larger in the day 3 group compared to the day 1 group. The organ of Corti on the basal turn showed evidence of damage and the number of surviving outer hair cells was significantly lower in the basal and middle turn areas of the hearing loss groups relative to controls. Five and three candidate miRNAs for each CN and IC were selected based on microarray analysis and quantitative reverse transcription PCR (RT-qPCR). The data confirmed that even short-term acoustic stimulation can lead to changes in neuroplasticity. Further studies are needed to validate the role of these candidate miRNAs. Such miRNAs may be used in the early diagnosis and treatment of neural plasticity of the central auditory pathway after acute NIHL.


Assuntos
Núcleo Coclear , Perda Auditiva Provocada por Ruído/metabolismo , Colículos Inferiores , MicroRNAs/metabolismo , Plasticidade Neuronal , Animais , Núcleo Coclear/metabolismo , Núcleo Coclear/patologia , Potenciais Evocados Auditivos do Tronco Encefálico , Colículos Inferiores/metabolismo , Colículos Inferiores/patologia , Masculino , Órgão Espiral/patologia , Ratos , Ratos Sprague-Dawley
7.
Front Neural Circuits ; 14: 43, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32765226

RESUMO

The inferior colliculus processes nearly all ascending auditory information. Most collicular cells respond to sound, and for a majority of these cells, the responses can be modulated by acetylcholine (ACh). The cholinergic effects are varied and, for the most part, the underlying mechanisms are unknown. The major source of cholinergic input to the inferior colliculus is the pedunculopontine tegmental nucleus (PPT), part of the pontomesencephalic tegmentum known for projections to the thalamus and roles in arousal and the sleep-wake cycle. Characterization of PPT inputs to the inferior colliculus has been complicated by the mixed neurotransmitter population within the PPT. Using selective viral-tract tracing techniques in a ChAT-Cre Long Evans rat, the present study characterizes the distribution and targets of cholinergic projections from PPT to the inferior colliculus. Following the deposit of viral vector in one PPT, cholinergic axons studded with boutons were present bilaterally in the inferior colliculus, with the greater density of axons and boutons ipsilateral to the injection site. On both sides, cholinergic axons were present throughout the inferior colliculus, distributing boutons to the central nucleus, lateral cortex, and dorsal cortex. In each inferior colliculus (IC) subdivision, the cholinergic PPT axons appear to contact both GABAergic and glutamatergic neurons. These findings suggest cholinergic projections from the PPT have a widespread influence over the IC, likely affecting many aspects of midbrain auditory processing. Moreover, the effects are likely to be mediated by direct cholinergic actions on both excitatory and inhibitory circuits in the inferior colliculus.


Assuntos
Neurônios Colinérgicos/metabolismo , Colículos Inferiores/metabolismo , Neurônios/metabolismo , Núcleo Tegmental Pedunculopontino/metabolismo , Animais , Axônios/metabolismo , Axônios/patologia , Neurônios Colinérgicos/patologia , Colículos Inferiores/citologia , Colículos Inferiores/patologia , Técnicas de Rastreamento Neuroanatômico , Neurônios/patologia , Núcleo Tegmental Pedunculopontino/citologia , Núcleo Tegmental Pedunculopontino/patologia , Ratos , Ratos Long-Evans
8.
Hear Res ; 391: 107957, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32278945

RESUMO

We examined the effect of acoustic trauma on the spontaneous activities of the glutamatergic and GABAergic neurons in the inferior colliculus (IC) of mice. Optogenetics was used to identify the neuron type. In control animals, the spontaneous firing rate was higher in GABAergic neurons than in glutamatergic neurons. However, in the animals with acoustic trauma, the balance of spontaneous activities between glutamatergic and GABAergic neurons was inverted. The spontaneous firing rate was enhanced in glutamatergic neurons only, with bursting episodes occurring frequently. Moreover, the spike shapes of GABAergic and glutamatergic neurons were modified differently in both cell types. These results suggested that the acoustic trauma induced plastic changes in the neuronal circuits in the IC and altered the balance of the activities of excitatory and inhibitory neurons. This aberrant excitatory-inhibitory balance in the IC might underpin tinnitus perception.


Assuntos
Neurônios GABAérgicos/metabolismo , Ácido Glutâmico/metabolismo , Perda Auditiva Provocada por Ruído/metabolismo , Colículos Inferiores/metabolismo , Inibição Neural , Plasticidade Neuronal , Transmissão Sináptica , Animais , Modelos Animais de Doenças , Potenciais Evocados Auditivos do Tronco Encefálico , Feminino , Neurônios GABAérgicos/patologia , Perda Auditiva Provocada por Ruído/etiologia , Perda Auditiva Provocada por Ruído/patologia , Perda Auditiva Provocada por Ruído/fisiopatologia , Colículos Inferiores/patologia , Colículos Inferiores/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Ruído
9.
Hear Res ; 377: 318-329, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30878270

RESUMO

It is well known that quality of hearing decreases with increasing age due to changes in the peripheral or central auditory pathway. Along with the decrease in the number of neurons the neurotransmitter profile is also affected in the various parts of the auditory system. Particularly, changes in the inhibitory neurons in the inferior colliculus (IC) are known to affect quality of hearing with aging. To date, there is no information about the status of the inhibitory neurotransmitter GABA in the human IC during aging. We have collected and processed inferior colliculi of persons aged 11-97 years at the time of death for morphometry and immunohistochemical expression of glutamic acid decarboxylase (GAD67) and parvalbumin. We used unbiased stereology to estimate the number of cresyl-violet and immunostained neurons. Quantitative real-time PCR was used to measure the relative expression of the GAD67 mRNA. We found that the number of total, GABAergic and PV-positive neurons significantly decreased with increasing age (p < 0.05). The proportion of GAD67-ir neurons to total number of neurons was also negatively associated with increasing age (p = 0.004), but there was no change observed in the proportion of PV-ir neurons relative to GABAergic neurons (p = 0.25). Further, the fold change in the levels of GAD67 mRNA was negatively correlated to age (p = 0.024). We conclude that the poorer quality of hearing with increasing age may be due to decreased expression of inhibitory neurotransmitters and the decline in the number of inhibitory neurons in the IC.


Assuntos
Envelhecimento/patologia , Vias Auditivas/patologia , Neurônios GABAérgicos/patologia , Colículos Inferiores/patologia , Presbiacusia/patologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/metabolismo , Vias Auditivas/química , Vias Auditivas/fisiopatologia , Morte Celular , Criança , Feminino , Neurônios GABAérgicos/química , Glutamato Descarboxilase/análise , Glutamato Descarboxilase/genética , Audição , Humanos , Colículos Inferiores/química , Colículos Inferiores/fisiopatologia , Masculino , Pessoa de Meia-Idade , Parvalbuminas/análise , Presbiacusia/metabolismo , Presbiacusia/fisiopatologia , Adulto Jovem , Ácido gama-Aminobutírico/análise
10.
Neuroscience ; 396: 79-93, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30458220

RESUMO

Prenatal exposure to the antiepileptic valproic acid (VPA) is associated with an increased risk of autism spectrum disorder (ASD) in humans and is used as an animal model of ASD. The majority of individuals with ASD exhibit adverse reactions to sensory stimuli and auditory dysfunction. Previous studies of animals exposed to VPA reveal abnormal neuronal responses to sound and mapping of sound frequency in the cerebral cortex and hyperactivation, hypoplasia and abnormal neuronal morphology in the cochlear nuclei (CN) and superior olivary complex (SOC). Herein, we examine the neuronal populations in the lateral lemniscus and inferior colliculus in animals exposed in utero to VPA. We used a combination of morphometric techniques, histochemistry and immunofluorescence to examine the nuclei of the lateral lemniscus (NLL) and the central nucleus of the inferior colliculus (CNIC). We found that the VPA exposure resulted in larger neurons in the CNIC and the dorsal nucleus of the lateral lemniscus (DNLL). However, we found that there were significantly fewer neurons throughout all nuclei examined in the auditory brainstem of VPA-exposed animals. Additionally, we found significantly fewer calbindin-immunopositive neurons in the DNLL. VPA exposure had no impact on the proportions of perineuronal nets in the NLL or CNIC. Finally, consistent with our observations in the CN and SOC, VPA exposure resulted in fewer dopaminergic terminals in the CNIC. Together, these results indicate that in utero VPA exposure significantly impacts structure and function of nearly the entire central auditory pathway.


Assuntos
Vias Auditivas/efeitos dos fármacos , Mesencéfalo/efeitos dos fármacos , Mesencéfalo/patologia , Neurônios/efeitos dos fármacos , Neurônios/patologia , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/patologia , Ácido Valproico/efeitos adversos , Animais , Transtorno do Espectro Autista/patologia , Calbindinas/metabolismo , Contagem de Células , Neurônios Dopaminérgicos/patologia , Feminino , Colículos Inferiores/efeitos dos fármacos , Colículos Inferiores/patologia , Masculino , Neurônios/metabolismo , Gravidez , Ratos
11.
Epilepsy Behav ; 88: 227-234, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30316149

RESUMO

It is known that audiogenic seizure (AGS) expression is based on the activation of the midbrain structures such as the inferior colliculus (IC). It was demonstrated that excessive sound exposure during the postnatal developments of the IC in rats led to AGS susceptibility in adulthood, which correlated with underdevelopment of the IC. In adult rodents, noise overstimulation induced apoptosis in the IC. The purpose of this study was to investigate postnatal development of the IC in rats genetically prone to AGS and to check if audiogenic kindling would activate apoptosis and/or proliferation in the IC. In our study, we used inbred audiogenic Krushinsky-Molodkina (KM) rats, which are characterized by age-dependent seizure expression. Analysis of postnatal development showed the increased number of proliferating cells in the IC central nucleus of KM rats on the 14th postnatal day (P14) in comparison with those of Wistar rats. Moreover, we also observed increased apoptosis level and decreased general cell population in the IC central nucleus. These data pointed towards a delayed development of the IC in KM rats. Analysis of the IC central nucleus of KM rat after audiogenic kindling for a week, with one AGS per day, demonstrated dramatically increased cell death, which was accompanied with a reduction of general cell population. Audiogenic kindling also decreased proliferation in the IC central nucleus. However, a week after the last AGS, the number of proliferating cells was increased, which supposes a certain compensatory mechanism to prevent cell loss.


Assuntos
Apoptose/fisiologia , Proliferação de Células/fisiologia , Epilepsia Reflexa/fisiopatologia , Colículos Inferiores/fisiopatologia , Estimulação Acústica/efeitos adversos , Animais , Epilepsia Reflexa/patologia , Feminino , Colículos Inferiores/crescimento & desenvolvimento , Colículos Inferiores/patologia , Excitação Neurológica/fisiologia , Masculino , Ratos , Ratos Endogâmicos , Ratos Wistar
12.
Hear Res ; 367: 207-212, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29954642

RESUMO

Neural plasticity is a characteristic of the brain that helps it adapt to changes in sensory input. We hypothesize that auditory deafferentation may induce plastic changes in the cytoskeleton of the neurons in the inferior colliculus (IC). In this study, we evaluated the dynamic status of neurofilament (NF) phosphorylation in the IC after hearing loss. We induced auditory deafferentation via unilateral or bilateral cochlear ablation in rats, aged 4 weeks. To evaluate cytoskeletal changes in neurons, we evaluated mRNA fold changes in NF heavy chain expression, non-phosphorylated NF protein fold changes using SMI-32 antibody, and the ratio of SMI-32 immunoreactive (SMI-32-ir) neurons to the total neuronal population in the IC at 4 and 12 weeks after deafness. In the bilateral deafness (BD) group, the ratios of SMI-32-ir neurons significantly increased at 4 weeks after ablation in the right and left IC (6.1 ±â€¯4.4%, 5.0 ±â€¯3.4%, respectively), compared with age-matched controls (P < 0.01, P < 0.01). At 12 weeks after ablation, the ratio of SMI-32 positive neurons was higher (right, 3.4 ±â€¯2.0%; left, 3.2 ±â€¯2.3%) than that in the age-matched control group, albeit not significant in the right and left side (P = 0.38, P = 0.24, respectively). Consistent with the results of the ratio of SMI-32-ir neurons, SMI-32-ir protein expression was increased at 4 weeks after BD, and the changes at 12 weeks after bilateral ablation were not significant in the right or left IC. The age-matched control fold changes of NF mRNA expression after bilateral deafness were not significant at 4 and 12 weeks after deafness in right and left IC. Unilateral deafness did not induce significant change of NF mRNA expression, SMI-32-ir protein expression, and the ratio of SMI-32-ir neurons in the IC at 4 and 12 weeks after hearing loss. Bilateral auditory deafferentation induces structural changes in the neuronal cytoskeleton within the IC, which is prominent at 4 weeks after BD. The structural remodeling of neurons stabilized at 12 weeks after BD. Unlike BD, unilateral auditory deafferentation did not affect the dynamic status of NFs in the IC.


Assuntos
Cóclea/inervação , Citoesqueleto/patologia , Surdez/patologia , Denervação/métodos , Colículos Inferiores/patologia , Plasticidade Neuronal , Neurônios/patologia , Animais , Citoesqueleto/metabolismo , Surdez/genética , Surdez/metabolismo , Surdez/fisiopatologia , Modelos Animais de Doenças , Regulação da Expressão Gênica , Colículos Inferiores/metabolismo , Colículos Inferiores/fisiopatologia , Masculino , Proteínas de Neurofilamentos/genética , Proteínas de Neurofilamentos/metabolismo , Neurônios/metabolismo , Fosforilação , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Fatores de Tempo
13.
Toxicol Appl Pharmacol ; 355: 28-42, 2018 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-29932956

RESUMO

Acute exposure to high concentrations of H2S causes severe brain injury and long-term neurological disorders, but the mechanisms involved are not known. To better understand the cellular and molecular mechanisms involved in acute H2S-induced neurodegeneration we used a broad-spectrum proteomic analysis approach to identify key molecules and molecular pathways involved in the pathogenesis of acute H2S-induced neurotoxicity and neurodegeneration. Mice were subjected to acute inhalation exposure of up to750 ppm of H2S. H2S induced behavioral deficits and severe lesions including hemorrhage in the inferior colliculus (IC). The IC was microdissected for proteomic analysis. Tandem mass tags (TMT) liquid chromatography mass spectrometry (LC-MS/MS)-based quantitative proteomics was applied for protein identification and quantitation. LC-MS/MS identified 598, 562, and 546 altered proteomic changes at 2 h, and on days 2 and 4 post-H2S exposure, respectively. Of these, 77 proteomic changes were statistically significant at any of the 3 time points. Mass spectrometry data were subjected to Perseus 1.5.5.3 statistical analysis, and gene ontology heat map clustering. Expressions of several key molecules were verified to confirm H2S-dependent proteomics changes. Webgestalt pathway overrepresentation enrichment analysis with Panther engine revealed H2S exposure disrupted several biological processes including metabotropic glutamate receptor group 1 and inflammation mediated by chemokine and cytokine signaling pathways among others. Further analysis showed that energy metabolism, integrity of blood-brain barrier, hypoxic, and oxidative stress signaling pathways were also implicated. Collectively, this broad-spectrum proteomics data has provided important clues to follow up in future studies to further elucidate mechanisms of H2S-induced neurotoxicity.


Assuntos
Sulfeto de Hidrogênio/toxicidade , Colículos Inferiores/metabolismo , Colículos Inferiores/patologia , Síndromes Neurotóxicas/genética , Síndromes Neurotóxicas/patologia , Proteômica , Animais , Comportamento Animal/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Exposição por Inalação , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Convulsões/induzido quimicamente , Transdução de Sinais/efeitos dos fármacos
14.
BMC Vet Res ; 13(1): 255, 2017 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-28821261

RESUMO

BACKGROUND: Canine visceral leishmaniasis (CVL) is endemic in São Luís Maranhão/Brazil and it leads a varied clinical picture, including neurological signs. RESULTS: Histopathological evaluation showed that 14 dogs exhibited pathological alterations in at least one of the analyzed areas. Of these, mononuclear inflammatory reaction was the most frequent, although other lesions, such as hemorrhage, chromatolysis and gliosis were also observed. The presence of L. infantum amastigotes was confirmed in eight dogs, identified in four regions: telencephalon, hippocampus, thalamus and caudal colliculus, but only one presented neurological signs. Polymerase chain reaction results detected the DNA of the parasite in 11 samples from seven dogs. The positive areas were the telencephalon, thalamus, hippocampus, cerebellum, caudal and rostral colliculus. CONCLUSION: These results reveal that during canine visceral leishmaniasis, the central nervous system may display some alterations, without necessarily exhibiting clinical neurological manifestations. In addition, the L. infantum parasite has the ability to cross the blood brain barrier and penetrate the central nervous system.


Assuntos
Sistema Nervoso Central/parasitologia , Doenças do Cão/parasitologia , Leishmania infantum , Leishmaniose Visceral/veterinária , Animais , Sistema Nervoso Central/patologia , DNA de Protozoário/genética , Doenças do Cão/patologia , Cães , Feminino , Hipocampo/parasitologia , Hipocampo/patologia , Colículos Inferiores/parasitologia , Colículos Inferiores/patologia , Leishmania infantum/genética , Leishmaniose Visceral/parasitologia , Leishmaniose Visceral/patologia , Masculino , Reação em Cadeia da Polimerase/veterinária , Telencéfalo/parasitologia , Telencéfalo/patologia , Tálamo/parasitologia , Tálamo/patologia
15.
Epilepsy Behav ; 71(Pt B): 238-242, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-27993512

RESUMO

Herpes virus technology involving manipulation of GAD65 was used to study effects on audiogenic seizures (AGS). Audiogenic seizure behaviors were examined following injections of replication-defective herpes simplex virus (HSV-1) vectors incorporating sense or antisense toward GAD65 along with 10% lac-Z into the central nucleus of inferior colliculus (CNIC) of Long-Evans rats. In seizure-sensitive animals developmentally primed by intense sound exposure, injection of GAD65 in the sense orientation increased wild running latencies and reduced incidence of clonus compared with lac-Z only, unoperated, and vehicle seizure groups. In contrast, infection of CNIC with GAD65 antisense virus resulted in 100% incidence of wild running and clonus behaviors in AGS animals. Unprimed animals not operated continued to show uniform absence of seizure activity. Administration of GAD65 antisense virus into CNIC produced novel wild running and clonus behaviors in some unprimed animals. Staining for ß-galactosidase in all vector animals revealed no differences in pattern or numbers of immunoreactive cells at injection sites. Qualitatively, typical small and medium multipolar/stellate and medium fusiform neurons appeared in the CNIC of vector animals. These results demonstrate that HSV-1 vector constructs implanted into the CNIC can predictably influence incidence and severity of AGS and suggest that viral vectors can be useful in studying GABA mechanisms with potential for therapeutic application in epilepsy. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic".


Assuntos
Estimulação Acústica/efeitos adversos , Epilepsia Reflexa/induzido quimicamente , Glutamato Descarboxilase/toxicidade , Herpesvirus Humano 1 , Colículos Inferiores/efeitos dos fármacos , Convulsões/induzido quimicamente , Animais , Epilepsia Reflexa/patologia , Epilepsia Reflexa/fisiopatologia , Feminino , Glutamato Descarboxilase/administração & dosagem , Colículos Inferiores/patologia , Colículos Inferiores/fisiopatologia , Masculino , Neurônios/efeitos dos fármacos , Neurônios/patologia , Ratos , Ratos Long-Evans , Convulsões/fisiopatologia
16.
Epilepsy Behav ; 71(Pt B): 160-164, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-25812940

RESUMO

In this review of neuroanatomical studies of the genetically epilepsy-prone rat (GEPR), three main topics will be covered. First, the number of GABAergic neurons and total neurons in the inferior colliculus of GEPRs will be compared to those of the nonepileptic Sprague-Dawley rat. Next, the number of small neurons in the inferior colliculus will be described in both developmental and genetic analyses of GEPRs and their backcrosses. Last, results from two types of studies on the propagation pathways for audiogenic seizures in GEPRs will be shown. Together, these studies demonstrate a unique GABAergic, small neuron defect in the inferior colliculus of GEPRs that may play a vital role in the initiation and spread of seizure activity during audiogenic seizures. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic".


Assuntos
Estimulação Acústica/efeitos adversos , Epilepsia Reflexa/genética , Epilepsia Reflexa/patologia , Neurônios GABAérgicos/patologia , Colículos Inferiores/patologia , Animais , Epilepsia Reflexa/fisiopatologia , Colículos Inferiores/fisiopatologia , Ratos , Ratos Sprague-Dawley , Convulsões/genética , Convulsões/patologia , Convulsões/fisiopatologia
17.
Hear Res ; 332: 7-16, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26631689

RESUMO

There are powerful pathways descending from the auditory cortex (AC) to the inferior colliculus (IC), yet their function is not fully understood. The aim of this study is to examine the effects of a reversible cortical inactivation, achieved by cooling of the AC, on the responses of neurons in the rat IC. Extracellular single-unit or multi-unit activity was recorded in the IC of anaesthetized rats with a 16-channel multielectrode probe introduced along the IC dorso-ventral axis through the dorsal cortex (DCIC) to the central nucleus of the IC (CIC). Cooling of the AC produced an increase in spontaneous activity and magnitude of the sound-evoked response in 47% of the IC neurons. Maximal changes in the neuronal activity were observed in the DCIC and the central part of the CIC. The final segments of the sustained responses to 60 ms stimuli and the off responses were more affected than the onset segments. Inactivation of the AC resulted in a suppression of the post-excitatory inhibition and neuronal adaptation, which was reflected in a pronounced enhancement of synchronized responses to a series of fast repeated clicks. The response parameters recovered, at least partly, to the pre-cooling levels 1 h after the cooling cessation. The frequency tuning properties of the IC neurons did not show any significant changes during the cooling period. The results demonstrate that AC cooling inactivates excitatory corticofugal pathways and results in a less activated intrinsic inhibitory network in the IC.


Assuntos
Córtex Auditivo/fisiopatologia , Regulação da Temperatura Corporal , Hipotermia Induzida , Colículos Inferiores/fisiopatologia , Estimulação Acústica , Adaptação Fisiológica , Animais , Córtex Auditivo/metabolismo , Córtex Auditivo/patologia , Vias Auditivas/fisiopatologia , Potenciais Evocados Auditivos , Feminino , Neurônios GABAérgicos/metabolismo , Colículos Inferiores/metabolismo , Colículos Inferiores/patologia , Inibição Neural , Ratos Long-Evans , Fatores de Tempo
18.
Brain Struct Funct ; 221(1): 617-29, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25408549

RESUMO

In previous studies (Grécová et al., Eur J Neurosci 29:1921-1930, 2009; Bures et al., Eur J Neurosci 32:155-164, 2010), we demonstrated that after an early postnatal short noise exposure (8 min 125 dB, day 14) changes in the frequency tuning curves as well as changes in the coding of sound intensity are present in the inferior colliculus (IC) of adult rats. In this study, we analyze on the basis of the Golgi-Cox method the morphology of neurons in the IC, the medial geniculate body (MGB) and the auditory cortex (AC) of 3-month-old Long-Evans rats exposed to identical noise at postnatal day 14 and compare the results to littermate controls. In rats exposed to noise as pups, the mean total length of the neuronal tree was found to be larger in the external cortex and the central nucleus of the IC and in the ventral division of the MGB. In addition, the numerical density of dendritic spines was decreased on the branches of neurons in the ventral division of the MGB in noise-exposed animals. In the AC, the mean total length of the apical dendritic segments of pyramidal neurons was significantly shorter in noise-exposed rats, however, only slight differences with respect to controls were observed in the length of basal dendrites of pyramidal cells as well as in the neuronal trees of AC non-pyramidal neurons. The numerical density of dendritic spines on the branches of pyramidal AC neurons was lower in exposed rats than in controls. These findings demonstrate that early postnatal short noise exposure can induce permanent changes in the development of neurons in the central auditory system, which apparently represent morphological correlates of functional plasticity.


Assuntos
Córtex Auditivo/patologia , Corpos Geniculados/patologia , Colículos Inferiores/patologia , Neurônios/patologia , Ruído/efeitos adversos , Estimulação Acústica , Fatores Etários , Animais , Animais Recém-Nascidos , Córtex Auditivo/crescimento & desenvolvimento , Vias Auditivas/patologia , Espinhas Dendríticas/patologia , Corpos Geniculados/crescimento & desenvolvimento , Colículos Inferiores/crescimento & desenvolvimento , Rede Nervosa/patologia , Plasticidade Neuronal , Células Piramidais/patologia , Ratos Long-Evans
19.
Brain Struct Funct ; 221(3): 1465-80, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25560311

RESUMO

While there is ample evidence that the structure and function of visual cortical areas are affected by early visual deprivation, little is known of how early blindness modifies subcortical relay and association thalamic nuclei, as well as mesencephalic structures. Therefore, in the present multicenter study, we used MRI to measure volume of the superior and inferior colliculi, as well as of the thalamic nuclei relaying sensory and motor information to the neocortex, parcellated according to atlas-based thalamo-cortical connections, in 29 individuals with congenital blindness of peripheral origin (17 M, age 35.7 ± 14.3 years) and 29 sighted subjects (17 M, age 31.9 ± 9.0). Blind participants showed an overall volume reduction in the left (p = 0.008) and right (p = 0.007) thalami, as compared to the sighted individuals. Specifically, the lateral geniculate (i.e., primary visual thalamic relay nucleus) was 40% reduced (left: p = 4 × 10(-6), right: p < 1 × 10(-6)), consistent with findings from animal studies. In addition, associated thalamic nuclei that project to temporal (left: p = 0.005, right: p = 0.005), prefrontal (left: p = 0.010, right: p = 0.014), occipital (left: p = 0.005, right: p = 0.023), and right premotor (p = 0.024) cortical regions were also significantly reduced in the congenitally blind group. Conversely, volumes of the relay nuclei directly involved in auditory, motor, and somatosensory processing were not affected by visual deprivation. In contrast, no difference in volume was observed in either the superior or the inferior colliculus between the two groups. Our findings indicate that visual loss since birth leads to selective volumetric changes within diencephalic, but not mesencephalic, structures. Both changes in reciprocal cortico-thalamic connections or modifications in the intrinsic connectivity between relay and association nuclei of the thalamus may contribute to explain these alterations in thalamic volumes. Sparing of the superior colliculi is in line with their composite, multisensory projections, and with their not exclusive visual nature.


Assuntos
Cegueira/congênito , Diencéfalo/patologia , Mesencéfalo/patologia , Adulto , Feminino , Humanos , Colículos Inferiores/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neocórtex/patologia , Colículos Superiores/patologia , Tálamo/patologia , Adulto Jovem
20.
Brain Pathol ; 26(2): 186-98, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25990815

RESUMO

Maturation of the auditory pathway is dependent on the central nervous system myelination and it can be affected by pathologies such as neonatal hypoxic ischemic (HI) encephalopathy. Our aim was to evaluate the functional integrity of the auditory pathway and to visualize, by histological and cellular methods, the damage to the brainstem using a neonatal rat model of HI brain injury. To carry out this morphofunctional evaluation, we studied the effects of the administration of the antioxidants nicotine, melatonin, resveratrol and docosahexaenoic acid after hypoxia-ischemia on the inferior colliculus and the auditory pathway. We found that the integrity of the auditory pathway in the brainstem was altered as a consequence of the HI insult. Thus, the auditory brainstem response (ABR) showed increased I-V and III-V wave latencies. At a histological level, HI altered the morphology of the inferior colliculus neurons, astrocytes and oligodendricytes, and at a molecular level, the mitochondria membrane potential and integrity was altered during the first hours after the HI and reactive oxygen species (ROS) activity is increased 12 h after the injury in the brainstem. Following antioxidant treatment, ABR interpeak latency intervals were restored and the body and brain weight was recovered as well as the morphology of the inferior colliculus that was similar to the control group. Our results support the hypothesis that antioxidant treatments have a protective effect on the functional changes of the auditory pathway and on the morphological damage which occurs after HI insult.


Assuntos
Antioxidantes/farmacologia , Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Colículos Inferiores/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Animais , Animais Recém-Nascidos , Astrócitos/efeitos dos fármacos , Astrócitos/patologia , Astrócitos/fisiologia , Peso Corporal , Modelos Animais de Doenças , Ácidos Docosa-Hexaenoicos/farmacologia , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Gliose/tratamento farmacológico , Gliose/patologia , Gliose/fisiopatologia , Hipóxia-Isquemia Encefálica/patologia , Hipóxia-Isquemia Encefálica/fisiopatologia , Colículos Inferiores/crescimento & desenvolvimento , Colículos Inferiores/patologia , Colículos Inferiores/fisiopatologia , Melatonina/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/patologia , Neurônios/fisiologia , Nicotina/farmacologia , Oligodendroglia/efeitos dos fármacos , Oligodendroglia/patologia , Oligodendroglia/fisiologia , Tamanho do Órgão , Distribuição Aleatória , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Resveratrol , Estilbenos/farmacologia
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