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1.
Acta Neurochir Suppl ; 127: 69-75, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31407066

RESUMO

BACKGROUND: Subarachnoid hemorrhage (SAH) is a severe and emergent cerebrovascular disease, the prognosis of which usually very poor. Microthrombi formation highlighted with inflammation occurs early after SAH. As the main cause of DCI, microthrombosis associated with the prognosis of SAH. The aim of this study was to show HSP90 inhibitor 17-AAG effect on microthrombosis after SAH in rats. METHODS: Ninety-five SD rats were used for the experiment. For time course study, the rats were randomly divided into five groups: sham group and SAH group with different time point (1d, 2d, 3d, 5d). Endovascular perforation method was conducted for SAH model. Neurological score, SAH grade, and mortality were measured after SAH. The samples of the left hemisphere brain were collected. The expression of HSP90 was detected by Western blot. The microthrombosis after SAH in rats' brain was detected by immunohistochemistry. For mechanism study, rats were randomly divided into three groups: sham, SAH + vehicle, and SAH +17-AAG (n = 6/group). 17-AAG was given by intraperitoneal injection (80 mg/kg) 1 h after SAH. Neurological function were measured at 24 h after SAH. The expression of RIP3, NLRP3, ASC, and IL-1ß was measured by Western blot. Microthrombosis was detected by immunohistochemistry. RESULTS: Our results showed that the HSP90 protein level increased and peaked at 2 days after SAH. Microthrombosis caused by SAH was increased in 1 day and peaked at 2 days after SAH. Administration HSP90 specific inhibitor 17-AAG reduced expression of RIP3, NLRP3, ASC, and IL-1ß, reduced microthrombosis after SAH, and improved neurobehavior when compared to vehicle group. CONCLUSIONS: 17-AAG can ameliorate microthrombosis via HSP90/RIP3/NLRP3 pathway and improve neurobehavior after SAH.


Assuntos
Inibidores Enzimáticos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Hemorragia Subaracnóidea , Trombose , Animais , Córtex Cerebral , Inibidores Enzimáticos/farmacologia , Proteínas de Choque Térmico HSP90 , Inflamação , Ratos , Ratos Sprague-Dawley , Proteína Serina-Treonina Quinases de Interação com Receptores , Hemorragia Subaracnóidea/tratamento farmacológico , Hemorragia Subaracnóidea/metabolismo , Trombose/tratamento farmacológico
2.
Postepy Biochem ; 65(2): 135-142, 2019 06 06.
Artigo em Polonês | MEDLINE | ID: mdl-31642652

RESUMO

The thalamus is a major part of the diencephalon and a hub for integrating sensory, motor and emotional information. Thalamocortical neuronal loops are involved in processing of sensory stimuli, directing attention, regulating the level of conscious awareness and selecting behavioural responses. The establishment of topographic thalamo-cortical connections is critical for brain performance, and their dysfunctions can contribute to the development of mental disorders. Thalamic axon guidance is regulated by the expression of molecular cues along the way to the cortex. In this review we outline the guiding process from the early growth of thalamic axons to their topographic targeting to specific cortical areas.


Assuntos
Axônios/fisiologia , Córtex Cerebral/citologia , Tálamo/citologia
3.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(9): 1102-1107, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31657333

RESUMO

OBJECTIVE: To investigate the effects of fecal microbiota transplantation on septic gut flora and the cortex cholinergic anti-inflammatory pathway in rats. METHODS: Sixty clean grade male Sprague-Dawley (SD) rats were divided into normal saline (NS) control group, sepsis model group and fecal microbiota transplantation group by random number table, with 20 rats in each group. The rat model of sepsis was reproduced by injection of 10 mg/kg lipopolysaccharide (LPS) via tail vein, the rats in the NS control group was given the same amount of NS. The rats in the fecal microbiota transplantation group received nasogastric infusion of feces from healthy donor on the 1st day, 2 mL each time, for 3 times a day, the other two groups were given equal dose of NS by gavage. Fecal samples were collected on the 7th day after modeling, the levels of intestinal microbiota composition was determined using the 16SrDNA gene sequencing technology. The brain function was evaluated by electroencephalogram (EEG), and the proportion of each waveform in EEG was calculated. After sacrifice of rats, the brain tissues were harvested, the levels of protein expression of α7 nicotinic acetylcholine receptor (α7nAChR) were determined by Western Blot, and positive cells of Iba-1 in brain tissue were detected by immunohistochemistry method. The levels of interleukins (IL-6 and IL-1ß) and tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Seven days after the reproduction of the model, all rats in the NS control group survived, while 10 rats and 8 rats died in the sepsis model group and fecal microbiota transplantation group, respectively, with mortality rates of 50% and 40% respectively. Finally, there were 20 rats in the NS control group, 10 in the sepsis model group and 12 in the fecal microbiota transplantation group. Compared with the NS control group, the diversity and composition of intestinal flora were changed, the incidence of abnormal EEG increased significantly, the expression of α7nAchR in the cortex decreased significantly, and the levels of Iba-1, TNF-α, IL-6 and IL-1ß were significantly increased in the model group, suggested that the intestinal flora was dysbiosis, and severe inflammatory reaction occurred in the cerebral cortex, and brain function was impaired. Compared with the model group, the diversity of intestinal flora in the fecal microbiota transplantation group was significantly increased (species index: 510.24±58.76 vs. 282.50±47.42, Chao1 index: 852.75±25.24 vs. 705.50±46.50, both P < 0.05), the dysbiosis of intestinal flora at phylum, family, genus level induced by LPS were also significantly reversed, and with the improvement of intestinal flora, the incidence of abnormal EEG waveforms was lower in the fecal microbiota transplantation group compared with that in the model group [25.0% (3/12) vs. 80.0% (8/10), P < 0.05], and the expression of α7nAChR protein in the cerebral cortex was significantly increased (α7nAChR/ß-actin: 1.56±0.05 vs. 0.82±0.07, P < 0.05), immunohistochemistry analysis showed that Iba-1 positive expression of microglia decreased significantly, and cerebral cortex TNF-α, IL-6, IL-1ß levels were significantly decreased [TNF-α (ng/L): 6.28±0.61 vs. 12.02±0.54, IL-6 (ng/L): 28.26±3.15 vs. 60.58±4.62, IL-1ß (ng/L): 33.63±3.48 vs. 72.56±2.25, all P < 0.05]. CONCLUSIONS: The results reveal that fecal microbiota transplantation has remarkably modulated the dysbiosis of intestinal microbiota and activated cholinergic anti-inflammatory pathway, and ameliorate the brain dysfunction in septic rats.


Assuntos
Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Sepse , Animais , Anti-Inflamatórios , Córtex Cerebral , Colinérgicos , Masculino , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa
4.
Zhen Ci Yan Jiu ; 44(9): 632-6, 2019.
Artigo em Chinês | MEDLINE | ID: mdl-31532130

RESUMO

OBJECTIVE: To explore the involvement of miR-34a in cerebral cortex mediated anti-hyperalgesic effect of electroacupuncture (EA) in mice with neuropathic pain induced by chronic constriction injury (CCI) of sciatic nerve, so as to reveal its mechanisms underlying improvement of neuropathic pain. METHODS: A total of 75 male C57BL/6 mice were equally randomized into 3 groups: sham, CCI model and CCI+EA (n=25 in each group). Mice of the sham group received simple separation of the right sciatic nerve without ligation. The CCI model was established by liagation of the right sciatic nerve. EA (2 Hz /15 Hz, 1 mA) was applied to bilateral "Zusanli" (ST36) and "Sanyinjiao" (SP9) for 30 min, once every other day. The mechanical and thermal pain threshold of the bilateral hind-paws was detected at the 3rd, 5th and 7th day after modeling, and the expression of miR-34a of bilateral cerebral cortex tissues and that of p53 protein of the left cerebral cortex were determined by using quantitive real time PCR and Western blot, respectively. RESULTS: The mechnical paw withdrawal frequency were significantly higher and the thermal paw withdrawal latencies (PWLs) were significantly shorter at the affected hind-limb (rather than at the healthy hind limb) on day 3, 5 and 7 in the CCI model group than those in the sham group (P<0.05), and considerably reversed at the affected hind-limb (rather than at the healthy hind limb) in the EA group than in the CCI model group (P<0.05), suggesting an analgesic effect of EA intervention. After modeling, the expression levels of miR-34a and p53 on day 3, 5 and 7 were significantly up-regulated in the left cerebral cortex tissue (rather than in the right cerebral cortex) of the CCI model group in comparison with the sham group (P<0.05). After EA intervention, the up-regulated expression levels of miR-34a and p53 in the left cerebral cortex tissue (rather than in the right cerebral cortex) were obviously suppressed in the EA group relevant to the CCI model group (P<0.05). CONCLUSION: EA stimulation of ST36 and SP9 can down-regulate the expression of miR-34a and p53 in the contra-lateral cerebral cortex tissue of the CCI mice, which may contribute to its anti-hyperalgesic effect.


Assuntos
Eletroacupuntura , Neuralgia , Animais , Córtex Cerebral , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs , Proteína Supressora de Tumor p53
5.
Brain Nerve ; 71(9): 993-1002, 2019 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-31506401

RESUMO

Joint attention behaviors involve sharing attention with others to an object or event by means of eye-gazing or pointing, which form the common basis for communication. There are two types of these behaviors: responding to joint attention (RJA) and initiating joint attention (IJA). RJA is the ability to follow the gaze of others, suggesting reception of a social signal from others; IJA is the ability to voluntarily direct the attention of others, to share the experience of an object or event, suggesting transmission of a social signal to others. Infants experience these roles (as signal receiver and signal transmitter) throughout the first year of life and learn social cognitive skills. Recent neuroimaging studies indicate that joint attention is supported by widely distributed neural systems with nodes in the dorsomedial prefrontal cortex, the orbitofrontal cortex and insula, the anterior and posterior cingulate cortex, the superior temporal cortex, the precuneus and parietal cortex, and the amygdala and striatum.


Assuntos
Atenção , Encéfalo/fisiologia , Comportamento Social , Córtex Cerebral , Humanos , Lactente , Lobo Parietal , Córtex Pré-Frontal , Lobo Temporal
6.
Medicine (Baltimore) ; 98(36): e17070, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31490406

RESUMO

Periventricular nodular heterotopia (PNH) is the most common type of epileptogenic neuronal migration disorder, and often presents with epilepsy and reading disability. The functional role of ectopic nodules has been widely studied. However, the associated structural cortical and subcortical volumetric alterations have not been well characterized. Moreover, it is unknown whether a correlation between volumetric changes and behavioral problems exists.40 subjects with bilateral PNH and 40 matched healthy controls were enrolled in this study. The total cerebral, gray matter, white matter, and cerebrospinal fluid (CSF) volumes were compared between the two groups. Furthermore, structural and functional correlations were evaluated between volumetric changes and reading disability.There were no significant differences detected in total cerebral, gray matter or CSF volumes between the two groups, but there was a significant trend of larger gray-matter volume in PNH. Specifically, smaller white matter volumes were found in the PNH patients. Moreover, the volume of white matter was negatively related to time in the digit rapid naming task and a similar but insignificant trend was seen between the volume of gray matter and backward digit span.These findings suggest that reading disability exists in our sample of bilateral PNH. Periventricular nodules would have normally migrated to the overlying cortex. However, the total cerebral, gray matter, and CSF volumes were unaffected. Alterations in neuronal migration may have an impact in the white matter associated reading dysfluency, that is, visually normal.


Assuntos
Córtex Cerebral/diagnóstico por imagem , Dislexia/diagnóstico por imagem , Dislexia/etiologia , Heterotopia Nodular Periventricular/complicações , Heterotopia Nodular Periventricular/diagnóstico por imagem , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Filaminas/genética , Humanos , Imagem por Ressonância Magnética , Masculino , Heterotopia Nodular Periventricular/genética , Adulto Jovem
8.
J Assoc Physicians India ; 67(7): 78-80, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31559778

RESUMO

Alexia without agraphia (also called pure alexia or word blindness) was the first of the disconnection syndromes to be described. It results from the loss of visual input to the language area without involvement of the language area. The most common cause is occlusion of the left posterior cerebral artery with involvement of left occipital cortex and the splenium of corpus callosum. However, it can also be caused by any lesion affecting the splenium of corpus callosum disrupting the white matter tracts from the left visual cortex to the angular gyrus. We hereby describe five cases of alexia without agraphia, of which three are due to involvement of the left occipital cortex and splenium, and two are due to involvement of the splenium of corpus callosum alone.


Assuntos
Alexia Pura , Córtex Cerebral , Corpo Caloso , Humanos , Lobo Occipital
9.
Anticancer Res ; 39(9): 4905-4909, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519594

RESUMO

BACKGROUND/AIM: The differentiation between cerebral metastases (CM) and high-grade gliomas (HGG) can be difficult on magnetic resonance imaging (MRI). The aim of this study was to evaluate the usefulness of searching two MRI signs (signal alteration in the adjacent cortex, SAAC, and peripheral rim sign, PRS), in order to distinguish between these entities. PATIENTS AND METHODS: A total of 61 patients were retrospectively enrolled (28 HGG, 33 CM). Fluid Attenuated Inversion Recovery (FLAIR) sequences were used to assess SAAC and contrast-enhanced T1-weighted sequences for PRS. RESULTS: A positive SAAC sign was present in 61% of HGG, and 12% of CM. Conversely, in SAAC-negative lesions, PRS was observed in 78% of CM and in 32% of HGG. Their association had a higher frequency in HGG than in the CM group (21 vs. 3%). CONCLUSION: While SAAC is specific for HGG and PRS, in the absence of SAAC, is relatively specific for CMs, their combined presence is highly suggestive of HGG.


Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/secundário , Córtex Cerebral/patologia , Glioma/diagnóstico , Imagem por Ressonância Magnética , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Curva ROC , Intensificação de Imagem Radiográfica , Reprodutibilidade dos Testes
10.
Nat Neurosci ; 22(10): 1677-1686, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31551604

RESUMO

When experts are immersed in a task, do their brains prioritize task-related activity? Most efforts to understand neural activity during well-learned tasks focus on cognitive computations and task-related movements. We wondered whether task-performing animals explore a broader movement landscape and how this impacts neural activity. We characterized movements using video and other sensors and measured neural activity using widefield and two-photon imaging. Cortex-wide activity was dominated by movements, especially uninstructed movements not required for the task. Some uninstructed movements were aligned to trial events. Accounting for them revealed that neurons with similar trial-averaged activity often reflected utterly different combinations of cognitive and movement variables. Other movements occurred idiosyncratically, accounting for trial-by-trial fluctuations that are often considered 'noise'. This held true throughout task-learning and for extracellular Neuropixels recordings that included subcortical areas. Our observations argue that animals execute expert decisions while performing richly varied, uninstructed movements that profoundly shape neural activity.


Assuntos
Cognição/fisiologia , Movimento/fisiologia , Neurônios/fisiologia , Animais , Percepção Auditiva/fisiologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiologia , Tomada de Decisões/fisiologia , Modelos Lineares , Camundongos , Camundongos Endogâmicos C57BL , Neuroimagem , Desempenho Psicomotor/fisiologia , Percepção Visual/fisiologia
11.
Sheng Li Xue Bao ; 71(4): 581-587, 2019 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-31440755

RESUMO

The purpose of this study was to establish a method to record the dynamic process of vascular regeneration and remodeling in rat cerebral ischemic regions. An animal brain window model was established to continuously observe the changes of rat cortical vascular ischemia in vivo, and the model of cerebral ischemia was established by photochemical embolization. Optical coherence tomography (OCT) was performed to record the formation of vascular blockage and the injury and regeneration of small vessels during cerebral ischemia recovery. The results showed that 30 min of laser irradiation could completely block the cortical vessels in rats. Within 24-48 h after ischemia, the degree of brain injury was the greatest, and the number of blood vessels in the ischemic region reached the minimum. Then the blocked blood vessels began to be dredged, and the small blood vessels around the ischemic area began to regenerate. Small blood vessels in the superficial/deep layers of the cortex disappeared significantly after laser irradiation. During 10 d after ischemia, the blocked blood vessels were gradually dredged and recovered. On the 10th day after laser irradiation, a large number of neovascularization appeared in the superficial layer of cortex, but the deep vessels did not recover. These results indicate that the method established in this study can observe the changes of blood vessel in cerebral ischemic region continuously, which lays a foundation for further quantitative study on the dynamics of embolized blood vessels and peripheral capillaries during the recovery of cerebral ischemia.


Assuntos
Isquemia Encefálica , Encéfalo/irrigação sanguínea , Córtex Cerebral/irrigação sanguínea , Regeneração , Animais , Ratos
12.
Chem Commun (Camb) ; 55(67): 9955-9958, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31364619

RESUMO

A silver nanocluster-based ratiometric fluorescent nanosensor was developed for the determination of ATP in the cerebrospinal fluid of a mouse brain. Using this useful tool with good stability and high selectivity as well as a wide linear detection range, it was found that the ATP concentration in a mouse brain with Alzheimer's disease was 2300-fold higher than that in a normal one.


Assuntos
Trifosfato de Adenosina/líquido cefalorraquidiano , Química Encefálica , DNA/química , Corantes Fluorescentes/química , Nanopartículas Metálicas/química , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Encéfalo/citologia , Encéfalo/patologia , Córtex Cerebral/química , Hipocampo/química , Camundongos , Conformação de Ácido Nucleico , Prata/química , Espectrometria de Fluorescência/métodos
13.
Minerva Med ; 110(5): 455-463, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31368292

RESUMO

Peripheral neuropathies are frequently encountered in clinical practice and are associated with a major impairment in quality of life. However, their management remains poor, and current therapies are often burdened with major side effects and can present poor efficacy on pain and functionality. Therefore, it has been suggested that the combination of two or more different drugs may improve analgesic efficacy and reduce side effects. Tricortin® 1000 is formulated with 12 mg of Brain cortex phospholipid liposomes + 1000 µg of Cyanocobalamin injectable solution (PL+CNCbl) for intramuscular use and is indicated in the treatment of poly-algo-neuropathic syndromes. This combination exerts a marked neurotrophic action by promoting the synthesis of endogenous phospholipids; moreover, the peculiar formulation optimizes the delivery of CNCbl which has analgesic and neurotrophic action. This paper discusses the pharmacotherapy of peripheral neuropathies, including low-back pain, neck pain, postherpetic neuropathy (PHN) and focuses on the fixed dose combination PL+CNCbl clinical efficacy in association with other treatments or in monotherapy.


Assuntos
Analgésicos/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Fosfolipídeos/uso terapêutico , Vitamina B 12/uso terapêutico , Analgésicos/administração & dosagem , Analgésicos/efeitos adversos , Córtex Cerebral/química , Ensaios Clínicos como Assunto , Combinação de Medicamentos , Humanos , Injeções Intramusculares , Lipossomos , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/efeitos adversos , Doenças do Sistema Nervoso Periférico/etiologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Fosfolipídeos/administração & dosagem , Fosfolipídeos/efeitos adversos , Vitamina B 12/administração & dosagem , Vitamina B 12/efeitos adversos
14.
Nat Commun ; 10(1): 3096, 2019 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-31363096

RESUMO

Natural communication often occurs in dialogue, differentially engaging auditory and sensorimotor brain regions during listening and speaking. However, previous attempts to decode speech directly from the human brain typically consider listening or speaking tasks in isolation. Here, human participants listened to questions and responded aloud with answers while we used high-density electrocorticography (ECoG) recordings to detect when they heard or said an utterance and to then decode the utterance's identity. Because certain answers were only plausible responses to certain questions, we could dynamically update the prior probabilities of each answer using the decoded question likelihoods as context. We decode produced and perceived utterances with accuracy rates as high as 61% and 76%, respectively (chance is 7% and 20%). Contextual integration of decoded question likelihoods significantly improves answer decoding. These results demonstrate real-time decoding of speech in an interactive, conversational setting, which has important implications for patients who are unable to communicate.


Assuntos
Mapeamento Encefálico/métodos , Córtex Cerebral/fisiologia , Fala/fisiologia , Interfaces Cérebro-Computador , Eletrocorticografia/instrumentação , Eletrocorticografia/métodos , Eletrodos Implantados , Epilepsia/diagnóstico , Epilepsia/fisiopatologia , Feminino , Humanos , Fatores de Tempo
15.
Arkh Patol ; 81(4): 59-65, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31407720

RESUMO

Involutional changes in the cerebral cortex substantially affect the activity of the cortex itself and the function of target organs. This necessitates pharmacological correction of age-related diseases, primarily a high level of cell death. OBJECTIVE: To investigate the role of cytoflavin in mechanisms for the apoptotic regulation of cerebral cortical cells during physiological and pathological aging (in the presence of HER-2/neu overexpression). MATERIAL AND METHODS: HER-2/neu transgenic mice were used; wild-type FVB/N mice served as controls. The levels of apoptosis (TUNEL) and the expression of its associated proteins (p53, CD95, Mcl-1, p-AKT, and p-ERK) (Western blotting) were estimated in the sensorimotor cortex. RESULTS: Activation of fundamental AKT and ERK survival pathways promotes a low level of cell death in young FVB/N mice; the extrinsic receptor mechanism of apoptosis is observed to be initiated by aging. The high p-AKT levels in the cortical cells provide suppressed cell death in transgenic mice regardless of their age. After cytoflavin administration, the old wild-type mice show a lower level of apoptosis in the cortical neurons apparently due to the increased expression of the anti-apoptotic protein Mcl-1, while the old transgenic mice exhibited suppression of the AKT and ERK survival pathways and, accordingly, activation of the extrinsic receptor and p53-dependent apoptosis pathways. CONCLUSION: Thus, cytoflavin exerts a pronounced neuroprotective effect during physiological and accelerated aging, while its effect on the level of neuronal apoptosis is ambiguous and depends on the genetic line of animals. So, this is a moderate stimulation of apoptosis when its level is low in HER-2/neu mice with a high level of carcinogenesis, as well as a decrease in the high level of apoptosis in old wild-type animals, which prevents neurodegeneration.


Assuntos
Envelhecimento , Córtex Cerebral , Mononucleotídeo de Flavina , Inosina Difosfato , Niacinamida , Succinatos , Animais , Apoptose , Córtex Cerebral/efeitos dos fármacos , Modelos Animais de Doenças , Combinação de Medicamentos , Feminino , Mononucleotídeo de Flavina/farmacologia , Inosina Difosfato/farmacologia , Camundongos , Niacinamida/farmacologia , Succinatos/farmacologia
16.
Postgrad Med ; 131(7): 509-522, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31422718

RESUMO

Objectives: Visual hallucinations (VH) are common in Lewy body disease (LBD), and have been associated with cognitive and structural brain alterations. Evidence so far concerns mainly Parkinson's disease (PD), but little is known about symptom-specific pathophysiological mechanisms across the LBD spectrum, especially related to the presence of dementia. The aim of the present pilot study was to investigate the neuroanatomical, and neuropsychological characteristics related to VH in two forms of LBD, namely dementia with Lewy bodies (DLB) and PD without dementia. Methods: Whole brain voxel-based morphometry (VBM) analyses on 3D MRI acquired structural brain scans, and neuropsychological testing were performed on 28 clinically diagnosed DLB (11 with VH, 17 NVH), and 24 PD (9 with VH, and 15 NVH) patients. In order to assess differences in gray matter (GM) regional volumes, and cognitive performance, hallucinating patients for each group were compared with corresponding non-hallucinating ones. Results: DLB patients with VH presented significantly worse visual attention deficits compared to those without, which persisted even when controlling for visual perception. Whole brain VBM analysis revealed decreased GM volume in DLB with VH in the right superior and medial frontal gyri, putamen, caudate nucleus and insula. Subcortical regional volumes were also significantly associated with visual attention performance. Hallucinating PD patients, instead, presented more severe executive dysfunction, but VBM showed no volumetric differences between the two PD subgroups. Post hoc region of interest analyses revealed striatal GM loss in PD with VH. Conclusion: Frontal and striatal GM atrophy may contribute to the emergence of VH in DLB, which may be fostered by the more severe attention deficits. Striatal GM loss and executive dysfunction, instead, appeared to underlie VH in PD without dementia.


Assuntos
Núcleo Caudado/diagnóstico por imagem , Lobo Frontal/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Alucinações/diagnóstico por imagem , Doença por Corpos de Lewy/diagnóstico por imagem , Doença de Parkinson/diagnóstico por imagem , Putamen/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Atenção , Estudos de Casos e Controles , Núcleo Caudado/patologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Feminino , Lobo Frontal/patologia , Substância Cinzenta/patologia , Alucinações/psicologia , Humanos , Doença por Corpos de Lewy/psicologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tamanho do Órgão , Doença de Parkinson/psicologia , Putamen/patologia , Percepção Visual
17.
Nat Neurosci ; 22(9): 1424-1437, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31455886

RESUMO

Triggering behavioral adaptation upon the detection of adversity is crucial for survival. The insular cortex has been suggested to process emotions and homeostatic signals, but how the insular cortex detects internal states and mediates behavioral adaptation is poorly understood. By combining data from fiber photometry, optogenetics, awake two-photon calcium imaging and comprehensive whole-brain viral tracings, we here uncover a role for the posterior insula in processing aversive sensory stimuli and emotional and bodily states, as well as in exerting prominent top-down modulation of ongoing behaviors in mice. By employing projection-specific optogenetics, we describe an insula-to-central amygdala pathway to mediate anxiety-related behaviors, while an independent nucleus accumbens-projecting pathway regulates feeding upon changes in bodily state. Together, our data support a model in which the posterior insular cortex can shift behavioral strategies upon the detection of aversive internal states, providing a new entry point to understand how alterations in insula circuitry may contribute to neuropsychiatric conditions.


Assuntos
Adaptação Fisiológica/fisiologia , Comportamento Animal/fisiologia , Córtex Cerebral/fisiologia , Vias Neurais/fisiologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL
18.
Nat Neurosci ; 22(9): 1402-1412, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31455887

RESUMO

RNA editing critically regulates neurodevelopment and normal neuronal function. The global landscape of RNA editing was surveyed across 364 schizophrenia cases and 383 control postmortem brain samples from the CommonMind Consortium, comprising two regions: dorsolateral prefrontal cortex and anterior cingulate cortex. In schizophrenia, RNA editing sites in genes encoding AMPA-type glutamate receptors and postsynaptic density proteins were less edited, whereas those encoding translation initiation machinery were edited more. These sites replicate between brain regions, map to 3'-untranslated regions and intronic regions, share common sequence motifs and overlap with binding sites for RNA-binding proteins crucial for neurodevelopment. These findings cross-validate in hundreds of non-overlapping dorsolateral prefrontal cortex samples. Furthermore, ~30% of RNA editing sites associate with cis-regulatory variants (editing quantitative trait loci or edQTLs). Fine-mapping edQTLs with schizophrenia risk loci revealed co-localization of eleven edQTLs with six loci. The findings demonstrate widespread altered RNA editing in schizophrenia and its genetic regulation, and suggest a causal and mechanistic role of RNA editing in schizophrenia neuropathology.


Assuntos
Córtex Cerebral/metabolismo , Edição de RNA/genética , Esquizofrenia/genética , Córtex Cerebral/fisiopatologia , Estudos de Coortes , Estudo de Associação Genômica Ampla , Humanos , Locos de Características Quantitativas/genética
19.
Nat Methods ; 16(8): 778-786, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31363222

RESUMO

Point-scanning two-photon microscopy enables high-resolution imaging within scattering specimens such as the mammalian brain, but sequential acquisition of voxels fundamentally limits its speed. We developed a two-photon imaging technique that scans lines of excitation across a focal plane at multiple angles and computationally recovers high-resolution images, attaining voxel rates of over 1 billion Hz in structured samples. Using a static image as a prior for recording neural activity, we imaged visually evoked and spontaneous glutamate release across hundreds of dendritic spines in mice at depths over 250 µm and frame rates over 1 kHz. Dendritic glutamate transients in anesthetized mice are synchronized within spatially contiguous domains spanning tens of micrometers at frequencies ranging from 1-100 Hz. We demonstrate millisecond-resolved recordings of acetylcholine and voltage indicators, three-dimensional single-particle tracking and imaging in densely labeled cortex. Our method surpasses limits on the speed of raster-scanned imaging imposed by fluorescence lifetime.


Assuntos
Córtex Cerebral/fisiologia , Ácido Glutâmico/metabolismo , Neurônios/fisiologia , Tomografia/métodos , Animais , Cálcio/metabolismo , Córtex Cerebral/citologia , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/citologia , Fótons , Ratos
20.
Br J Anaesth ; 123(3): 298-308, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31277837

RESUMO

BACKGROUND: Emergence from sedation entails rapid increase in the levels of both awareness and wakefulness, the two axes of consciousness. Functional MRI (fMRI) studies of emergence from sedation often focus on the recovery period, with no description of the moment of emergence. We hypothesised that by focusing on the moment of emergence, novel insights, primarily about subcortical activity and increased wakefulness, will be gained. METHODS: We conducted a resting state fMRI analysis of 17 male subjects (20-40 yr old) gradually entering into and emerging from deep sedation (average computed propofol concentrations of 2.41 and 1.11 µg ml-1, respectively), using target-controlled infusion of propofol. RESULTS: Functional connectivity analysis revealed a robust spatiotemporal signature of return of consciousness, in which subcortical seeds showed transient positive correlations that rapidly turned negative shortly after emergence. Elements of this signature included four components of the ascending reticular activating system: the ventral tegmentum area, the locus coeruleus, median raphe, and the mammillary body. The involvement of the rostral dorsolateral pontine tegmentum, which is specifically impaired in comatose patients with pontine lesions, in emergence was previously unknown. CONCLUSIONS: Emergence from propofol sedation is characterised, and possibly driven, by a transient activation of brainstem loci. Some of these loci are known components of the ascending reticular activating system, whereas an additional locus was found that is also impaired in comatose patients.


Assuntos
Córtex Cerebral/efeitos dos fármacos , Sedação Profunda/métodos , Hipnóticos e Sedativos/farmacologia , Propofol/farmacologia , Adulto , Período de Recuperação da Anestesia , Mapeamento Encefálico/métodos , Tronco Encefálico/diagnóstico por imagem , Tronco Encefálico/efeitos dos fármacos , Tronco Encefálico/fisiologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiologia , Estado de Consciência/efeitos dos fármacos , Esquema de Medicação , Humanos , Hipnóticos e Sedativos/administração & dosagem , Imagem por Ressonância Magnética , Masculino , Rede Nervosa/efeitos dos fármacos , Propofol/administração & dosagem , Adulto Jovem
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