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1.
Neurobiol Aging ; 107: 142-152, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34433125

RESUMO

With the emergence of disease-modifying therapies for Parkinson's disease, reliable longitudinal markers are needed to quantify pathology and demonstrate disease progression. We developed the A53T-AAV rat model of synucleinopathy by combining longitudinal measures over 12 weeks. We first characterized the progression of the motor and dopaminergic deficits. Then, we monitored the disease progression using the [18F]FMT Positron Emission Tomography (PET) radiotracer. The nigral injection of A53T-AAV led to an increase in phosphorylated α-synuclein on S129, a progressive accumulation of α-synuclein aggregates, and a decrease of dopaminergic function associated with a deterioration of motor activity. The longitudinal monitoring of A53T-AAV rats with [18F]FMT PET showed a progressive reduction of the Kc outcome parameter in the caudate putamen from the lesioned side. Interestingly, the progressive reduction in the [18F]FMT PET signal correlated with defects in the stepping test. In conclusion, we established a progressive rat model of α-synuclein pathology which monitors the deficit longitudinally using both the [18F]FMT PET tracer and behavioral parameters, 2 features that have strong relevance for translational approaches.


Assuntos
Dependovirus , Neurônios Dopaminérgicos/patologia , Neurônios Dopaminérgicos/fisiologia , Atividade Motora , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/fisiopatologia , Sinucleinopatias/diagnóstico por imagem , Sinucleinopatias/fisiopatologia , Animais , Modelos Animais de Doenças , Progressão da Doença , Radioisótopos de Flúor , Masculino , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Fosforilação , Tomografia por Emissão de Pósitrons , Agregados Proteicos , Ratos Sprague-Dawley , Sinucleinopatias/metabolismo , Sinucleinopatias/patologia , Tirosina , alfa-Sinucleína/metabolismo
2.
Int J Mol Sci ; 21(19)2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32977526

RESUMO

Seizures are common in patients with high-grade gliomas (30-60%) and approximately 15-30% of glioblastoma (GB) patients develop drug-resistant epilepsy. Reliable animal models are needed to develop adequate treatments for glioma-related epilepsy. Therefore, fifteen rats were inoculated with F98 GB cells (GB group) and four rats with vehicle only (control group) in the right entorhinal cortex. MRI was performed to visualize tumor presence. A subset of seven GB and two control rats were implanted with recording electrodes to determine the occurrence of epileptic seizures with video-EEG recording over multiple days. In a subset of rats, tumor size and expression of tumor markers were investigated with histology or mRNA in situ hybridization. Tumors were visible on MRI six days post-inoculation. Time-dependent changes in tumor morphology and size were visible on MRI. Epileptic seizures were detected in all GB rats monitored with video-EEG. Twenty-one days after inoculation, rats were euthanized based on signs of discomfort and pain. This study describes, for the first time, reproducible tumor growth and spontaneous seizures upon inoculation of F98 cells in the rat entorhinal cortex. The development of this new model of GB-related epilepsy may be valuable to design new therapies against tumor growth and associated epileptic seizures.


Assuntos
Neoplasias Encefálicas , Eletroencefalografia , Epilepsia , Glioma , Neoplasias Experimentais , Animais , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/fisiopatologia , Linhagem Celular Tumoral , Epilepsia/metabolismo , Epilepsia/patologia , Epilepsia/fisiopatologia , Glioma/metabolismo , Glioma/patologia , Glioma/fisiopatologia , Masculino , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Neoplasias Experimentais/fisiopatologia , Ratos , Ratos Endogâmicos F344
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