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1.
Neuroimage ; 225: 117456, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33069863

RESUMO

Hallucinogenic agents have been proposed as potent antidepressants; this includes the serotonin (5-HT) receptor 2A agonist psilocybin. In human subjects, psilocybin alters functional connectivity (FC) within the default-mode network (DMN), a constellation of inter-connected regions that displays altered FC in depressive disorders. In this study, we investigated the effects of psilocybin on FC across the entire brain with a view to investigate underlying mechanisms. Psilocybin effects were investigated in lightly-anaesthetized mice using resting-state fMRI. Dual-regression analysis identified reduced FC within the ventral striatum in psilocybin- relative to vehicle-treated mice. Refinement of the analysis using spatial references derived from both gene expression maps and viral tracer projection fields revealed two distinct effects of psilocybin: it increased FC between 5-HT-associated networks and cortical areas, including elements of the murine DMN, thalamus, and midbrain; it decreased FC within dopamine (DA)-associated striatal networks. These results suggest that interactions between 5-HT- and DA-regulated neural networks contribute to the neural and therefore psychological effects of psilocybin. Furthermore, they highlight how information on molecular expression patterns and structural connectivity can assist in the interpretation of pharmaco-fMRI findings.


Assuntos
Encéfalo/efeitos dos fármacos , Rede de Modo Padrão/efeitos dos fármacos , Psilocibina/farmacologia , Agonistas do Receptor 5-HT2 de Serotonina/farmacologia , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Corpo Estriado/diagnóstico por imagem , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Rede de Modo Padrão/diagnóstico por imagem , Rede de Modo Padrão/metabolismo , Dopamina/metabolismo , Neuroimagem Funcional , Imageamento por Ressonância Magnética , Mesencéfalo/diagnóstico por imagem , Mesencéfalo/efeitos dos fármacos , Mesencéfalo/metabolismo , Camundongos , Vias Neurais/diagnóstico por imagem , Vias Neurais/efeitos dos fármacos , Vias Neurais/metabolismo , Descanso , Serotonina/metabolismo , Tálamo/diagnóstico por imagem , Tálamo/efeitos dos fármacos , Tálamo/metabolismo
2.
Neuroimage ; 205: 116278, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31614221

RESUMO

Preclinical applications of resting-state functional magnetic resonance imaging (rsfMRI) offer the possibility to non-invasively probe whole-brain network dynamics and to investigate the determinants of altered network signatures observed in human studies. Mouse rsfMRI has been increasingly adopted by numerous laboratories worldwide. Here we describe a multi-centre comparison of 17 mouse rsfMRI datasets via a common image processing and analysis pipeline. Despite prominent cross-laboratory differences in equipment and imaging procedures, we report the reproducible identification of several large-scale resting-state networks (RSN), including a mouse default-mode network, in the majority of datasets. A combination of factors was associated with enhanced reproducibility in functional connectivity parameter estimation, including animal handling procedures and equipment performance. RSN spatial specificity was enhanced in datasets acquired at higher field strength, with cryoprobes, in ventilated animals, and under medetomidine-isoflurane combination sedation. Our work describes a set of representative RSNs in the mouse brain and highlights key experimental parameters that can critically guide the design and analysis of future rodent rsfMRI investigations.


Assuntos
Encéfalo/fisiologia , Conectoma/métodos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Rede Nervosa/fisiologia , Animais , Encéfalo/diagnóstico por imagem , Conectoma/normas , Feminino , Processamento de Imagem Assistida por Computador/normas , Imageamento por Ressonância Magnética/normas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Rede Nervosa/diagnóstico por imagem , Reprodutibilidade dos Testes
3.
Pain ; 160(1): 151-159, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30161041

RESUMO

Cancer-induced bone pain is abundant among advanced-stage cancer patients and arises from a primary tumor in the bone or skeletal metastasis of common cancer types such as breast, lung, or prostate cancer. Recently, antibodies targeting nerve growth factor (NGF) have been shown to effectively relieve neuropathic and inflammatory pain states in mice and in humans. Although efficacy has been shown in mice on a behavioral level, effectiveness in preventing pain-induced functional rearrangements in the central nervous system has not been shown. Therefore, we assessed longitudinal whole-brain functional connectivity using resting-state functional magnetic resonance imaging in a mouse model of cancer-induced bone pain. We found functional connectivity between major hubs of ascending and descending pain pathways such as the periaqueductal gray, amygdala, thalamus, and cortical somatosensory regions to be affected by a developing cancer pain state. These changes could be successfully prevented through prospective administration of a monoclonal anti-NGF antibody (mAb911). This indicates efficacy of anti-NGF treatment to prevent pain-induced adaptations in brain functional networks after persistent nociceptive input from cancer-induced bone pain. In addition, it highlights the suitability of resting-state functional magnetic resonance imaging readouts as an indicator of treatment response on the basis of longitudinal functional network changes.


Assuntos
Anticorpos/uso terapêutico , Neoplasias Ósseas/complicações , Dor do Câncer/tratamento farmacológico , Dor do Câncer/etiologia , Fator de Crescimento Neural/imunologia , Animais , Neoplasias Ósseas/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Dor do Câncer/diagnóstico por imagem , Modelos Animais de Doenças , Feminino , Imageamento por Ressonância Magnética , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Pain ; 159(4): 719-727, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29319607

RESUMO

Functional neuroimaging has emerged as attractive option for characterizing pain states complementing behavioral readouts or clinical assessment. In particular, resting-state functional magnetic resonance imaging (rs-fMRI) enables monitoring of functional adaptations across the brain, for example, in response to chronic nociceptive input. We have used rs-fMRI in a mouse model of chronic pain from breast cancer-derived tibial bone metastases to identify pain-induced alterations in functional connectivity. Combined assessment of behavioral readouts allowed for defining a trajectory as model function for extracting pain-specific functional connectivity changes from the fMRI data reflective of a chronic pain state. Cingulate and prefrontal cortices as well as the ventral striatum were identified as predominantly affected regions, in line with findings from clinical and preclinical studies. Inhibition of the peripheral bone remodeling processes by antiosteolytic therapy led to a reduction of pain-induced network alterations, emphasizing the specificity of the functional readouts for a developing chronic pain state.


Assuntos
Neoplasias Ósseas/complicações , Neoplasias Ósseas/diagnóstico por imagem , Dor Crônica/etiologia , Imageamento por Ressonância Magnética , Animais , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Dor Crônica/diagnóstico por imagem , Dor Crônica/tratamento farmacológico , Modelos Animais de Doenças , Feminino , Processamento de Imagem Assistida por Computador , Camundongos , Camundongos Endogâmicos C57BL , Oxigênio/sangue , Medição da Dor , Descanso , Ácido Zoledrônico/uso terapêutico
5.
Mol Imaging Biol ; 18(2): 191-200, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26381672

RESUMO

PURPOSE: Assessing tumor vascular features including permeability and perfusion is essential for diagnostic and therapeutic purposes. The aim of this study was to compare fluorescence and magnetic resonance imaging (MRI)-based vascular readouts in subcutaneously implanted tumors in mice by simultaneous dynamic measurement of tracer uptake using a hybrid fluorescence molecular tomography (FMT)/MRI system. PROCEDURE: Vascular permeability was measured using a mixture of extravascular imaging agents, GdDOTA and the dye Cy5.5, and perfusion using a mixture of intravascular agents, Endorem and a fluorescent probe (Angiosense). Dynamic fluorescence reflectance imaging (dFRI) was integrated into the hybrid system for high temporal resolution. RESULTS: Excellent correspondence between uptake curves of Cy5.5/GdDOTA and Endorem/Angiosense has been found with correlation coefficients R > 0.98. The two modalities revealed good agreement regarding permeability coefficients and centers-of-gravity of the imaging agent distribution. CONCLUSION: The FMT/dFRI protocol presented is able to accurately map physiological processes and poses an attractive alternative to MRI for characterizing tumor neoangiogenesis.


Assuntos
Permeabilidade Capilar , Imageamento por Ressonância Magnética/métodos , Neoplasias/irrigação sanguínea , Perfusão , Animais , Feminino , Fluorescência , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias/patologia
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