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1.
Atten Percept Psychophys ; 82(8): 3973-3992, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32935292

RESUMO

Correctly assessing the emotional state of others is a crucial part of social interaction. While facial expressions provide much information, faces are often not viewed in isolation, but occur with concurrent sounds, usually voices, which also provide information about the emotion being portrayed. Many studies have examined the crossmodal processing of faces and sounds, but results have been mixed, with different paradigms yielding different results. Using a psychophysical adaptation paradigm, we carried out a series of four experiments to determine whether there is a perceptual advantage when faces and voices match in emotion (congruent), versus when they do not match (incongruent). We presented a single face and a crowd of voices, a crowd of faces and a crowd of voices, a single face of reduced salience and a crowd of voices, and tested this last condition with and without attention directed to the emotion in the face. While we observed aftereffects in the hypothesized direction (adaptation to faces conveying positive emotion yielded negative, contrastive, perceptual aftereffects), we only found a congruent advantage (stronger adaptation effects) when faces were attended and of reduced salience, in line with the theory of inverse effectiveness.

2.
Brain Sci ; 9(8)2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31349644

RESUMO

One source of information we glean from everyday experience, which guides social interaction, is assessing the emotional state of others. Emotional state can be expressed through several modalities: body posture or movements, body odor, touch, facial expression, or the intonation in a voice. Much research has examined emotional processing within one sensory modality or the transfer of emotional processing from one modality to another. Yet, less is known regarding interactions across different modalities when perceiving emotions, despite our common experience of seeing emotion in a face while hearing the corresponding emotion in a voice. Our study examined if visual and auditory emotions of matched valence (congruent) conferred stronger perceptual and physiological effects compared to visual and auditory emotions of unmatched valence (incongruent). We quantified how exposure to emotional faces and/or voices altered perception using psychophysics and how it altered a physiological proxy for stress or arousal using salivary cortisol. While we found no significant advantage of congruent over incongruent emotions, we found that changes in cortisol were associated with perceptual changes. Following exposure to negative emotional content, larger decreases in cortisol, indicative of less stress, correlated with more positive perceptual after-effects, indicative of stronger biases to see neutral faces as happier.

3.
Front Hum Neurosci ; 12: 415, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30459579

RESUMO

Humans differ in their individual navigational performance, in part because successful navigation relies on several diverse abilities. One such navigational capability is path integration, the updating of position and orientation during movement, typically in a sparse, landmark-free environment. This study examined the relationship between path integration abilities and functional connectivity to several canonical intrinsic brain networks. Intrinsic networks within the brain reflect past inputs and communication as well as structural architecture. Individual differences in intrinsic connectivity have been observed for common networks, suggesting that these networks can inform our understanding of individual spatial abilities. Here, we examined individual differences in intrinsic connectivity using resting state magnetic resonance imaging (rsMRI). We tested path integration ability using a loop closure task, in which participants viewed a single video of movement in a circle trajectory in a sparse environment, and then indicated whether the video ended in the same location in which it started. To examine intrinsic brain networks, participants underwent a resting state scan. We found that better performance in the loop task was associated with increased connectivity during rest between the central executive network (CEN) and posterior hippocampus, parahippocampal cortex (PHC) and entorhinal cortex. We also found that connectivity between PHC and the default mode network (DMN) during rest was associated with better loop closure performance. The results indicate that interactions between medial temporal lobe (MTL) regions and intrinsic networks that involve prefrontal cortex (PFC) are important for path integration and navigation.

4.
Neurobiol Dis ; 82: 495-503, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26392287

RESUMO

Diminished lysosomal function can lead to abnormal cellular accumulation of specific proteins, including α-synuclein, contributing to disease pathogenesis of vulnerable neurons in Parkinson's disease (PD) and related α-synucleinopathies. GBA1 encodes for the lysosomal hydrolase glucocerebrosidase (GCase), and mutations in GBA1 are a prominent genetic risk factor for PD. Previous studies showed that in sporadic PD, and in normal aging, GCase brain activity is reduced and levels of corresponding glycolipid substrates are increased. The present study tested whether increasing GCase through AAV-GBA1 intra-cerebral gene delivery in two PD rodent models would reduce the accumulation of α-synuclein and protect midbrain dopamine neurons from α-synuclein-mediated neuronal damage. In the first model, transgenic mice overexpressing wildtype α-synuclein throughout the brain (ASO mice) were used, and in the second model, a rat model of selective dopamine neuron degeneration was induced by AAV-A53T mutant α-synuclein. In ASO mice, intra-cerebral AAV-GBA1 injections into several brain regions increased GCase activity and reduced the accumulation of α-synuclein in the substantia nigra and striatum. In rats, co-injection of AAV-GBA1 with AAV-A53T α-synuclein into the substantia nigra prevented α-synuclein-mediated degeneration of nigrostriatal dopamine neurons by 6 months. These neuroprotective effects were associated with altered protein expression of markers of autophagy. These experiments demonstrate, for the first time, the neuroprotective effects of increasing GCase against dopaminergic neuron degeneration, and support the development of therapeutics targeting GCase or other lysosomal genes to improve neuronal handling of α-synuclein.


Assuntos
Neurônios Dopaminérgicos/enzimologia , Terapia Genética/métodos , Glucosilceramidase/genética , Mesencéfalo/enzimologia , Doenças Neurodegenerativas/terapia , alfa-Sinucleína/metabolismo , Animais , Dependovirus/genética , Modelos Animais de Doenças , Dopamina/metabolismo , Neurônios Dopaminérgicos/patologia , Feminino , Vetores Genéticos , Glucosilceramidase/metabolismo , Humanos , Masculino , Mesencéfalo/patologia , Camundongos Transgênicos , Doenças Neurodegenerativas/enzimologia , Doenças Neurodegenerativas/patologia , Ratos Sprague-Dawley , alfa-Sinucleína/genética
5.
Antioxid Redox Signal ; 23(6): 550-64, 2015 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-26094487

RESUMO

AIMS: Loss-of-function mutations in GBA1, which cause the autosomal recessive lysosomal storage disease, Gaucher disease (GD), are also a key genetic risk factor for the α-synucleinopathies, including Parkinson's disease (PD) and dementia with Lewy bodies. GBA1 encodes for the lysosomal hydrolase glucocerebrosidase and reductions in this enzyme result in the accumulation of the glycolipid substrates glucosylceramide and glucosylsphingosine. Deficits in autophagy and lysosomal degradation pathways likely contribute to the pathological accumulation of α-synuclein in PD. In this report we used conduritol-ß-epoxide (CBE), a potent selective irreversible competitive inhibitor of glucocerebrosidase, to model reduced glucocerebrosidase activity in vivo, and tested whether sustained glucocerebrosidase inhibition in mice could induce neuropathological abnormalities including α-synucleinopathy, and neurodegeneration. RESULTS: Our data demonstrate that daily systemic CBE treatment over 28 days caused accumulation of insoluble α-synuclein aggregates in the substantia nigra, and altered levels of proteins involved in the autophagy lysosomal system. These neuropathological changes were paralleled by widespread neuroinflammation, upregulation of complement C1q, abnormalities in synaptic, axonal transport and cytoskeletal proteins, and neurodegeneration. INNOVATION: A reduction in brain GCase activity has been linked to sporadic PD and normal aging, and may contribute to the susceptibility of vulnerable neurons to degeneration. This report demonstrates that systemic reduction of GCase activity using chemical inhibition, leads to neuropathological changes in the brain reminiscent of α-synucleinopathy. CONCLUSIONS: These data reveal a link between reduced glucocerebrosidase and the development of α-synucleinopathy and pathophysiological abnormalities in mice, and support the development of GCase therapeutics to reduce α-synucleinopathy in PD and related disorders.


Assuntos
Complemento C1q/metabolismo , Glucosilceramidase/antagonistas & inibidores , Inositol/análogos & derivados , Microglia/fisiologia , Agregação Patológica de Proteínas/enzimologia , alfa-Sinucleína/metabolismo , Animais , Autofagia , Transporte Axonal , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Ativação do Complemento , Glucosilceramidase/metabolismo , Inositol/farmacologia , Masculino , Camundongos , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/enzimologia , Agregação Patológica de Proteínas/induzido quimicamente , Proteínas/metabolismo , Transmissão Sináptica
6.
Hum Mol Genet ; 23(17): 4510-27, 2014 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-24728190

RESUMO

A long-term goal of modeling Huntington's disease (HD) is to recapitulate the cardinal features of the disease in mice that express both mutant and wild-type (WT) huntingtin (Htt), as HD commonly manifests as a heterozygous condition in humans, and loss of WT Htt is associated with loss-of-function. In a new heterozygous Q175 knock-in (KI) mouse model, we performed an extensive evaluation of motor and cognitive functional deficits, neuropathological and biochemical changes and levels of proteins involved in synaptic function, the cytoskeleton and axonal transport, at 1-16 months of age. Motor deficits were apparent at 6 months of age in Q175 KI mice and at that time, postmortem striatal gamma-aminobutyric acid (GABA) levels were elevated and mutant Htt inclusions were present throughout the brain. From 6 months of age, levels of proteins associated with synaptic function, including SNAP-25, Rab3A and PSD-95, and with axonal transport and microtubules, including KIF3A, dynein and dynactin, were altered in the striatum, motor cortex, prefrontal cortex and hippocampus of Q175 KI mice, compared with WT levels. At 12-16 months of age, Q175 KI mice displayed motor and cognitive deficits, which were paralleled at postmortem by striatal atrophy, cortical thinning, degeneration of medium spiny neurons, dense mutant Htt inclusion formation, decreased striatal dopamine levels and loss of striatal brain-derived neurotrophic factor (BDNF). Data from this study indicate that the heterozygous Q175 KI mouse represents a realistic model for HD and also provides new insights into the specific and progressive synaptic, cytoskeletal and axonal transport protein abnormalities that may accompany the disease.


Assuntos
Transporte Axonal , Comportamento Animal , Doença de Huntington/genética , Doença de Huntington/patologia , Sinapses/metabolismo , Envelhecimento/patologia , Animais , Atrofia/genética , Atrofia/patologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Citoesqueleto/metabolismo , Modelos Animais de Doenças , Técnicas de Introdução de Genes , Heterozigoto , Corpos de Inclusão/metabolismo , Metaboloma , Camundongos , Camundongos Endogâmicos C57BL , Mutação/genética , Neostriado/metabolismo , Neostriado/patologia , Neurotransmissores/metabolismo , Receptor trkB/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo
7.
J Neurochem ; 119(6): 1173-82, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21955359

RESUMO

The chemokine BRAK/CXCL14 is an ancient member of the chemokine family whose functions in the brain are completely unknown. We examined the distribution of CXCL14 in the nervous system during development and in the adult. Generally speaking, CXCL14 was not expressed in the nervous system prior to birth, but it was expressed in the developing whisker follicles (E14.5) and subsequently in the hair follicles and skin. Postnatally, CXCL14 was also highly expressed in many regions of the brain, including the cortex, basal ganglia, septum and hippocampus. CXCL14 was also highly expressed in the dorsal root ganglia. We observed that in the hippocampal dentate gyrus (DG) CXCL14 was expressed by GABAergic interneurons. We demonstrated that CXCL14 inhibited GABAergic transmission to nestin-EGFP-expressing neural stem/progenitor cells in the adult DG. CXCL14 inhibited both the tonic and phasic effects of synaptically released GABA. In contrast CXCL12 enhanced the effects of GABA at these same synapses. CXCL14 increased [Ca(2+)](i) in neural stem cells cultured from the postnatal brain indicating that they expressed the CXCL14 receptor. These observations are consistent with the view that CXCL12 and CXCL14 may normally act as positive and negative regulators of the effects of GABA in the adult DG stem cell niche.


Assuntos
Quimiocinas CXC/metabolismo , Giro Denteado/anatomia & histologia , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Neurônios/fisiologia , Nicho de Células-Tronco/fisiologia , Transmissão Sináptica/fisiologia , 2-Amino-5-fosfonovalerato/farmacologia , Animais , Animais Recém-Nascidos , Cálcio/metabolismo , Quimiocina CXCL12/metabolismo , Quimiocina CXCL12/farmacologia , Quimiocinas CXC/genética , Quimiocinas CXC/farmacologia , Giro Denteado/crescimento & desenvolvimento , Embrião de Mamíferos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Regulação da Expressão Gênica no Desenvolvimento/genética , Glutamato Descarboxilase/metabolismo , Proteínas de Fluorescência Verde/genética , Técnicas In Vitro , Proteínas de Filamentos Intermediários/genética , Masculino , Camundongos , Camundongos Transgênicos , Proteínas do Tecido Nervoso/genética , Nestina , Neurônios/efeitos dos fármacos , Técnicas de Patch-Clamp , Quinoxalinas/farmacologia , RNA Mensageiro/metabolismo , Receptores CXCR/metabolismo , Nicho de Células-Tronco/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/genética
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