Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.409
Filtrar
1.
Life Sci ; 241: 117163, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31837337

RESUMO

AIMS: The high sugar and lipid content of the Western diet (WD) is associated with metabolic dysfunction, non-alcoholic steatohepatitis, and it is an established risk factor for neuropsychiatric disorders. Our previous studies reported negative effects of the WD on rodent emotionality, impulsivity, and sociability in adulthood. Here, we investigated the effect of the WD on motor coordination, novelty recognition, and affective behavior in mice as well as molecular and cellular endpoints in brain and peripheral tissues. MAIN METHODS: Female C57BL/6 J mice were fed the WD for three weeks and were investigated for glucose tolerance, insulin resistance, liver steatosis, and changes in motor coordination, object recognition, and despair behavior in the swim test. Lipids and liver injury markers, including aspartate-transaminase, alanine-transaminase and urea were measured in blood. Serotonin transporter (SERT) expression, the density of Iba1-positive cells and concentration of malondialdehyde were measured in brain. KEY FINDINGS: WD-fed mice exhibited impaired glucose tolerance and insulin resistance, a loss of motor coordination, deficits in novel object exploration and recognition, increased helplessness, dyslipidemia, as well as signs of a non-alcoholic steatohepatitis (NASH)-like syndrome: liver steatosis and increased liver injury markers. Importantly, these changes were accompanied by decreased SERT expression, elevated numbers of microglia cells and malondialdehyde levels in, and restricted to, the prefrontal cortex. SIGNIFICANCE: The WD induces a spectrum of behaviors that are more reminiscent of ADHD and ASD than previously recognized and suggests that, in addition to the impairment of impulsivity and sociability, the consumption of a WD might be expected to exacerbate motor dysfunction that is also known to be associated with adult ADHD and ASD.


Assuntos
Transtornos Cognitivos/etiologia , Dieta Ocidental/efeitos adversos , Inflamação/etiologia , Transtornos Motores/etiologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Córtex Pré-Frontal/patologia , Animais , Comportamento Animal , Transtornos Cognitivos/patologia , Feminino , Inflamação/patologia , Camundongos , Camundongos Endogâmicos C57BL , Transtornos Motores/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , Córtex Pré-Frontal/imunologia
2.
Nat Genet ; 51(11): 1637-1644, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31676860

RESUMO

Volumetric variations of the human brain are heritable and are associated with many brain-related complex traits. Here we performed genome-wide association studies (GWAS) of 101 brain volumetric phenotypes using the UK Biobank sample including 19,629 participants. GWAS identified 365 independent genetic variants exceeding a significance threshold of 4.9 × 10-10, adjusted for testing multiple phenotypes. A gene-based association study found 157 associated genes (124 new), and functional gene mapping analysis linked 146 additional genes. Many of the discovered genetic variants and genes have previously been implicated in cognitive and mental health traits. Through genome-wide polygenic-risk-score prediction, more than 6% of the phenotypic variance (P = 3.13 × 10-24) in four other independent studies could be explained by the UK Biobank GWAS results. In conclusion, our study identifies many new genetic associations at the variant, locus and gene levels and advances our understanding of the pleiotropy and genetic co-architecture between brain volumes and other traits.


Assuntos
Encéfalo/anatomia & histologia , Transtornos Cognitivos/genética , Marcadores Genéticos , Estudo de Associação Genômica Ampla , Transtornos Mentais/genética , Polimorfismo de Nucleotídeo Único , Característica Quantitativa Herdável , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/metabolismo , Criança , Pré-Escolar , Transtornos Cognitivos/patologia , Estudos de Coortes , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Desequilíbrio de Ligação , Masculino , Transtornos Mentais/patologia , Saúde Mental , Pessoa de Meia-Idade , Herança Multifatorial , Fenótipo , Reino Unido , Adulto Jovem
3.
Life Sci ; 237: 116932, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31606384

RESUMO

The prevalence of dementia worldwide is growing at an alarming rate. A number of studies and meta-analyses have provided evidence for increased risk of dementia in patients with metabolic syndrome (MS) as compared to persons without MS. However, there are some reports demonstrating a lack of association between MS and increased dementia risk. In this review, taking into account the potential role of individual MS components in the pathogenesis of MS-related cognitive dysfunction, we considered the underlying mechanisms in arterial hypertension, diabetes mellitus, dyslipidemia, and obesity. The pathogenesis of dementia in MS is multifactorial, involving both vascular injury and non-ischemic neuronal death due to neurodegeneration. Neurodegenerative and ischemic lesions do not simply coexist in the brain due to independent evolution, but rather exacerbate each other, leading to more severe consequences for cognition than would either pathology alone. In addition to universal mechanisms of cognitive dysfunction shared by all MS components, other pathogenetic pathways leading to cognitive deficits and dementia, which are specific for each component, also play a role. Examples of such component-specific pathogenetic pathways include central insulin resistance and hypoglycemia in diabetes, neuroinflammation and adipokine imbalance in obesity, as well as arteriolosclerosis and lipohyalinosis in arterial hypertension. A more detailed understanding of cognitive disorders based on the recognition of underlying molecular mechanisms will aid in the development of new methods for prevention and treatment of devastating cognitive problems in MS.


Assuntos
Transtornos Cognitivos/etiologia , Transtornos Cognitivos/patologia , Demência/etiologia , Demência/patologia , Síndrome Metabólica/complicações , Síndrome Metabólica/patologia , Animais , Humanos , Fatores de Risco , Transdução de Sinais
4.
Psychiatr Danub ; 31(Suppl 3): 517-519, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488783

RESUMO

BACKGROUND: In the literature we can find evidence that sex hormones are involved the alterations of cognition in schizophrenic patients. Another factor, which may have an impact on cognitive domains in this clinical group inflammatory processes. The objective of this review was to explore studies, in which the role of both immunological factors and sex hormones on cognitive functions in schizophrenia are analyzed. METHODS: The search of papers covering this topic in PubMed and Google Scholar was performed. RESULTS: Endocrine factors like: testosteron, estrogen, as well as immunomodulatory are observed to play a role in cognitive functioning in schizophrenia. CONCLUSIONS: More studies are necessary to confirm these possible co-relations.


Assuntos
Transtornos Cognitivos , Cognição , Hormônios Esteroides Gonadais , Inflamação , Esquizofrenia , Psicologia do Esquizofrênico , Transtornos Cognitivos/complicações , Transtornos Cognitivos/metabolismo , Transtornos Cognitivos/patologia , Hormônios Esteroides Gonadais/metabolismo , Humanos , Inflamação/metabolismo , Esquizofrenia/complicações , Esquizofrenia/metabolismo , Esquizofrenia/patologia
5.
Molecules ; 24(12)2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31226738

RESUMO

Alzheimer's disease (AD) is the most common type of dementia and is the leading cause of disability in elderly people worldwide. Current pharmacological therapies do not cure the disease, and for this reason, some pharmacotherapy studies have investigated preventive treatments focused on modifiable nutritional factors such as diet. Quercetin (Qc) is a flavonoid found in fruits and vegetables that has several biological properties. In this study, we evaluated the effect of chronic oral quercetin administration (100 mg/kg) on neurodegeneration markers and cognitive and emotional deficits in a triple transgenic Alzheimer's disease (3xTg-AD) mouse model using histological and behavioral analyses. Our results suggest that long-term (12 months) oral preventive treatment with quercetin has significant effects on ß-amyloidosis reduction and tends to decrease tauopathy in the hippocampus and amygdala. These decreases positively affected the cognitive functional recovery (without modifying the emotional skills) of 3xTg-AD mice. These findings suggest that preventive and chronic administration of Qc might help to delay the development of histopathological hallmarks and cognitive function deficits in AD.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Transtornos Cognitivos/tratamento farmacológico , Quercetina/farmacologia , Proteínas tau/genética , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Doença de Alzheimer/prevenção & controle , Peptídeos beta-Amiloides/genética , Precursor de Proteína beta-Amiloide/genética , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Transtornos Cognitivos/genética , Transtornos Cognitivos/patologia , Transtornos Cognitivos/prevenção & controle , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Humanos , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Transgênicos
6.
Orphanet J Rare Dis ; 14(1): 101, 2019 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-31060595

RESUMO

BACKGROUND/OBJECTIVES: Chediak-Higashi Disease (CHD) is a rare autosomal disorder, purported to have cognitive and neurological impairments. Prior descriptions of cognitive impairment, however, are solely based on subjective, unstructured observations rather than on formal neuropsychological measures. METHODS: Four pediatric and 14 adult patients with diagnostically confirmed CHD were administered a neuropsychological battery assessing memory, attention, processing speed, psychomotor speed, language fluency, executive function, and general intelligence. Nine of the adult patients received follow-up evaluations to elucidate the longitudinal progression or stability of cognition over time. RESULTS: Pediatric CHD patients performed within the average range. Adult patients, however, performed below average on nearly all measures administered, and endorsed subjective reports of learning difficulties and poor academic performance in childhood. In particular, patients struggled with memory and psychomotor speed tasks, with 75% or more of patients scoring in the bottom 2.3 percentile in these two domains. No significant declines in cognition were observed among the patients who completed follow-up evaluations (M = 39.90, SD = 8.03 months between visits). Exploratory analyses suggested that adult patients who had classic CHD and previously received bone marrow transplants (BMTs; n = 3) exhibited moderately greater cognitive impairment than adult patients who had atypical CHD and had not received BMTs (n = 10). CONCLUSIONS: Adult patients with CHD uniformly exhibit deficits in multiple domains, but in psychomotor speed and memory, in particular. Based on their neuropsychological profile, their ability to hold jobs and succeed in school may require support and special accommodations. The source of cognitive deficits is probably multifactorial including central nervous system involvement in CHD, and, for those transplanted, BMT-related side effects and complications. Absence of cognitive decline at three-year follow-up is encouraging but does not exclude progression at a slower time-scale. Future work should elucidate the possible effects and timing of BMT on cognition, as well as the mechanisms driving neuropsychological impairment in CHD.


Assuntos
Síndrome de Chediak-Higashi/patologia , Síndrome de Chediak-Higashi/fisiopatologia , Transtornos Cognitivos/patologia , Transtornos Cognitivos/fisiopatologia , Adolescente , Adulto , Transplante de Medula Óssea , Cognição/fisiologia , Feminino , Humanos , Deficiência Intelectual/patologia , Deficiência Intelectual/fisiopatologia , Masculino , Testes Neuropsicológicos , Neuropsicologia , Adulto Jovem
7.
Cell Mol Neurobiol ; 39(6): 857-869, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31089833

RESUMO

Status epilepticus without prompt seizure control always leads to neuronal death and long-term cognitive deficits, but effective intervention is still absent. Here, we found that hydrogen could alleviate the hippocampus-dependent spatial learning and memory deficit in lithium-pilocarpine model of status epilepticus in rats, as evidenced by the results in Morris water maze test. Hydrogen treatment downregulated the expression of necroptosis-related proteins, such as MLKL, phosphorylated-MLKL, and RIPK3 in hippocampus, and further protected neurons and astrocytes from necroptosis which was here first verified to occur in status epilepticus. Hydrogen also protected cells from apoptosis, which was indicated by the decreased cleaved-Caspase 3 expression. Meanwhile, Iba1+ microglial activation by status epilepticus was reduced by hydrogen treatment. These findings confirm the utility of hydrogen treatment in averting cell death including necroptosis and alleviating cognitive deficits caused by status epilepticus. Therefore, hydrogen may provide a potential and powerful clinical treatment for status epilepticus-related cognitive deficits.


Assuntos
Apoptose/efeitos dos fármacos , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/patologia , Hidrogênio/uso terapêutico , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/tratamento farmacológico , Animais , Região CA1 Hipocampal/efeitos dos fármacos , Região CA1 Hipocampal/patologia , Região CA1 Hipocampal/ultraestrutura , Transtornos Cognitivos/complicações , Transtornos Cognitivos/fisiopatologia , Modelos Animais de Doenças , Hidrogênio/farmacologia , Inflamação/patologia , Lítio , Masculino , Memória/efeitos dos fármacos , Necrose , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Pilocarpina , Ratos Sprague-Dawley , Aprendizagem Espacial/efeitos dos fármacos , Estado Epiléptico/complicações , Estado Epiléptico/patologia
8.
Neuron ; 103(2): 250-265.e8, 2019 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-31122677

RESUMO

Activity-dependent myelination is thought to contribute to adaptive neurological function. However, the mechanisms by which activity regulates myelination and the extent to which myelin plasticity contributes to non-motor cognitive functions remain incompletely understood. Using a mouse model of chemotherapy-related cognitive impairment (CRCI), we recently demonstrated that methotrexate (MTX) chemotherapy induces complex glial dysfunction for which microglial activation is central. Here, we demonstrate that remote MTX exposure blocks activity-regulated myelination. MTX decreases cortical Bdnf expression, which is restored by microglial depletion. Bdnf-TrkB signaling is a required component of activity-dependent myelination. Oligodendrocyte precursor cell (OPC)-specific TrkB deletion in chemotherapy-naive mice results in impaired cognitive behavioral performance. A small-molecule TrkB agonist rescues both myelination and cognitive impairment after MTX chemotherapy. This rescue after MTX depends on intact TrkB expression in OPCs. Taken together, these findings demonstrate a molecular mechanism required for adaptive myelination that is aberrant in CRCI due to microglial activation.


Assuntos
Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/patologia , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Bainha de Mielina/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Channelrhodopsins/genética , Channelrhodopsins/metabolismo , Transtornos Cognitivos/genética , Modelos Animais de Doenças , Humanos , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Bainha de Mielina/patologia , Bainha de Mielina/ultraestrutura , Células Precursoras de Oligodendrócitos/efeitos dos fármacos , Compostos Orgânicos/uso terapêutico , Proteínas Tirosina Quinases/genética , Proteínas Tirosina Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Ureia/análogos & derivados , Ureia/metabolismo
9.
J Int Med Res ; 47(6): 2471-2482, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31014147

RESUMO

OBJECTIVES: Carotid endarterectomy (CEA) is efficient in preventing stroke for patients with significant carotid stenosis, but results in mild cognitive dysfunction. Dexmedetomidine is neuroprotective in stroke models. We hypothesized that dexmedetomidine may improve cognition after CEA. METHODS: Forty-nine patients scheduled for elective CEA were randomly assigned to intravenous dexmedetomidine treatment group (n = 25) and control group C (normal saline, n = 24). Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MOCA), as well as lactate, TNF-α, IL-6, and BDNF levels in blood, were assessed before, during, and after surgery. RESULTS: MMSE and MOCA scores showed subtle decline in both groups at 24 hours postoperatively; this decline remained at 48 hours postoperatively in group C. Both scores were higher in group D than in group C at 48 and 72 hours postoperatively. TNF-α and IL-6 were lower from 5 minutes post-clamping through 24 hours postoperatively in group D; lactate was lower at 5 minutes post-clamping in group D. BDNF was higher from 5 minutes post-clamping through 1 hour postoperatively in both groups, and remained high in group D at 24 hours postoperatively. CONCLUSIONS: Dexmedetomidine improved recovery of cognition after CEA, potentially due to reduced inflammation and enhanced BDNF expression.


Assuntos
Isquemia Encefálica/prevenção & controle , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Estenose das Carótidas/cirurgia , Transtornos Cognitivos/tratamento farmacológico , Dexmedetomidina/uso terapêutico , Endarterectomia das Carótidas/efeitos adversos , Inflamação/prevenção & controle , Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/etiologia , Isquemia Encefálica/patologia , Estenose das Carótidas/patologia , Estudos de Casos e Controles , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/patologia , Feminino , Seguimentos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/etiologia , Inflamação/patologia , Masculino , Prognóstico
10.
Pituitary ; 22(3): 270-282, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30929221

RESUMO

Traumatic brain injury (TBI) causes substantial neurological disabilities and mental distress. Annual TBI incidence is in magnitude of millions, making it a global health challenge. Categorization of TBI into severe, moderate and mild by scores on the Glasgow coma scale (GCS) is based on clinical grounds and standard brain imaging (CT). Recent research focused on repeated mild TBI (sport and non-sport concussions) suggests that a considerable number of patients have long-term disabling neurocognitive and neurobehavioral sequelae. These relate to subtle neuronal injury (diffuse axonal injury) visible only by using advanced neuroimaging distinguishing microstructural tissue damage. With advanced MRI protocols better characterization of TBI is achievable. Diffusion tensor imaging (DTI) visualizes white matter pathology, susceptibility weight imaging (SWI) detects microscopic bleeding while functional magnetic resonance imaging (fMRI) provides closer understanding of cognitive disorders etc. However, advanced imaging is still not integrated in the clinical care of patients with TBI. Patients with chronic TBI may experience many somatic disorders, cognitive disturbances and mental complaints. The underlying pathophysiological mechanisms occurring in TBI are complex, brain injuries are highly heterogeneous and include neuroendocrine dysfunctions. Post-traumatic neuroendocrine dysfunctions received attention since the year 2000. Occurrence of TBI-related hypopituitarism does not correlate to severity of the GCS scores. Complete or partial hypopituitarism (isolated growth hormone (GH) deficiency as most frequent) may occur after mild TBI equally as after moderate-to-severe TBI. Many symptoms of hypopituitarism overlap with symptoms occurring in patients with chronic TBI, i.e. they have lower scores on neuropsychological examinations (cognitive disability) and have more symptoms of mental distress (depression and fatigue). The great challenges for the endocrinologist are: (1) detection of hypopituitarism in patients with TBI prospectively (in the acute phase and months to years after TBI), (2) assessment of the extent of cognitive impairment at baseline, and (3) monitoring of treatment effects (alteration of cognitive functioning and mental distress with hormone replacement therapy). Only few studies recently suggest that with growth hormone (rhGH) replacement in patients with chronic TBI and with abnormal GH secretion, cognitive performance may not change while symptoms related to depression and fatigue improve. Stagnation in post-TBI rehabilitation progress is recommended as a signal for clinical suspicion of neuroendocrine dysfunction. This remains a challenging area for more research.


Assuntos
Lesões Encefálicas Traumáticas/patologia , Encéfalo/patologia , Animais , Encéfalo/diagnóstico por imagem , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Transtornos Cognitivos/diagnóstico por imagem , Transtornos Cognitivos/patologia , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Testes Neuropsicológicos
11.
Neurology ; 92(17): e2015-e2026, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-30944239

RESUMO

OBJECTIVES: To investigate the independent and interaction effects of Alzheimer disease (AD) and Lewy body disease (LBD) on cognition and brain atrophy. METHODS: We consecutively recruited 38 controls and 108 patients with AD-related cognitive impairment (ADCI) and/or LBD-related cognitive impairment (LBCI) from university-based dementia and movement clinics. Diagnoses of ADCI and LBCI were supported by 18F-florbetaben PET and 18F-N-(3-fluoropropyl)-2ß-carbon ethoxy-3ß-(4-iodophenyl) nortropane-PET, respectively. There were 38 controls, 26 patients with pure ADCI (18 mild cognitive impairment [MCI] and 8 dementia), 28 patients with pure LBCI (13 MCI and 15 dementia), and 54 patients with mixed ADCI and LBCI (17 MCI and 37 dementia). We performed group-wise comparisons for neuropsychological z scores and regional cortical thickness. We also evaluated the effects of ADCI and LBCI using general linear models. RESULTS: Compared to the controls, patients in the pure ADCI group and pure LBCI group had focused cortical thinning in the bilateral entorhinal/right anterior temporal cortices and bilateral anteromedial temporal/basal frontal cortices, respectively, while the mixed disease group had additional cortical thinning in the widespread association cortices. The independent effects of ADCI and LBCI on regional cortical thinning overlapped in the widespread association cortices, especially at the bilateral temporoparietal junction and parietal cortices. ADCI and LBCI had independent detrimental effects on the copying item of the Rey-Osterrieth Complex Figure Test. CONCLUSIONS: Concomitant ADCI and LBCI are associated with the accentuation of neurodegeneration to widespread association cortices, and both diseases contribute to visuospatial dysfunction.


Assuntos
Doença de Alzheimer/patologia , Encéfalo/patologia , Transtornos Cognitivos/patologia , Cognição/fisiologia , Disfunção Cognitiva/patologia , Doença por Corpos de Lewy/patologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/psicologia , Atrofia/diagnóstico por imagem , Atrofia/patologia , Encéfalo/diagnóstico por imagem , Transtornos Cognitivos/diagnóstico por imagem , Transtornos Cognitivos/psicologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/psicologia , Feminino , Humanos , Doença por Corpos de Lewy/diagnóstico por imagem , Doença por Corpos de Lewy/psicologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons
12.
Behav Neurol ; 2019: 3248519, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30944661

RESUMO

There has been growing awareness of the correlation between an episode of traumatic brain injury (TBI) and the development of Alzheimer's disease (AD) later in life. It has been reported that TBI accelerated amyloid-ß (Aß) pathology and cognitive decline in the several lines of AD model mice. However, the short-term and long-term effects of TBI by the weight-drop method on amyloid-ß pathology and cognitive performance are unclear in wild-type (WT) mice. Hence, we examined AD-related histopathological changes and cognitive impairment after TBI in wild-type C57BL6J mice. Five- to seven-month-old WT mice were subjected to either TBI by the weight-drop method or a sham treatment. Seven days after TBI, the WT mice exhibited significantly lower spatial learning than the sham-treated WT mice. However, 28 days after TBI, the cognitive impairment in the TBI-treated WT mice recovered. Correspondingly, while significant amyloid-ß (Aß) plaques and amyloid precursor protein (APP) accumulation were observed in the TBI-treated mouse hippocampus 7 days after TBI, the Aß deposition was no longer apparent 28 days after TBI. Thus, TBI induced transient amyloid-ß deposition and acute cognitive impairments in the WT mice. The present study suggests that the TBI could be a risk factor for acute cognitive impairment even when genetic and hereditary predispositions are not involved. The system might be useful for evaluating and developing a pharmacological treatment for the acute cognitive deficits.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Lesões Encefálicas Traumáticas/metabolismo , Transtornos Cognitivos/patologia , Disfunção Cognitiva/patologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Lesões Encefálicas Traumáticas/patologia , Cognição/fisiologia , Transtornos Cognitivos/metabolismo , Disfunção Cognitiva/metabolismo , Modelos Animais de Doenças , Masculino , Camundongos Endogâmicos C57BL
13.
Horm Behav ; 112: 20-31, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30917909

RESUMO

Chronic exposure to stress during adolescent period has been demonstrated to impair cognitive functions and the dendritic morphology of pyramidal neurons in the rat hippocampal CA3 area. The present study investigated the combined protective effects of Spirulina platensis (SP), a supplement made from blue-green algae with neuroprotective properties, voluntary exercise (EX) and environmental enrichment (EE) against cognitive deficits, alternations in hippocampal BDNF levels, and abnormal neuronal remodeling in adult female rats (PND 60) induced by exposure to chronic restraint stress during adolescent period (PND 30-40). Rats were exposed to restraint stress (2 h/day for 10 days, PND 30-40). Then, the animals were subjected to treatment with SP (200 mg/kg/day), EX, EE and the combined treatments (SP + EX, and SP + EE) between PND 41 and 55 of age. Following the interventions, spatial learning and memory, passive avoidance performance, hippocampal dendritic morphology and BDNF levels were assessed. Results showed that plasma corticosterone levels increased at PND 40 and remained elevated at PND 55 and 70 in the stressed rats. Stressed rats showed deficits in spatial learning and memory and passive avoidance performance, decreased BDNF levels in the hippocampus, and reduced apical dendritic length and branch points of the CA3 pyramidal neurons. These deficits were alleviated by the SP, EX and EE, and the combined treatments, which accompanied with a decline in serum corticosterone in stressed animals. Some treatments even enhanced cognitive functions, and BDNF levels and neuroanatomical remodeling in the hippocampus of non-stressed animals. Our findings provide important evidences that physical activity, exposure to EE, and the SP treatment during adolescent period can protect against adolescent stress induced behavioral, biochemical and neuroanatomical impairments in adulthood.


Assuntos
Extratos Celulares/farmacologia , Transtornos Cognitivos/prevenção & controle , Plasticidade Neuronal , Condicionamento Físico Animal/fisiologia , Meio Social , Spirulina/química , Estresse Psicológico/complicações , Animais , Animais Recém-Nascidos , Aprendizagem da Esquiva/efeitos dos fármacos , Aprendizagem da Esquiva/fisiologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Cognição/efeitos dos fármacos , Cognição/fisiologia , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/patologia , Transtornos Cognitivos/fisiopatologia , /fisiologia , Feminino , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Hipocampo/fisiopatologia , Memória/efeitos dos fármacos , Memória/fisiologia , Plasticidade Neuronal/efeitos dos fármacos , Ratos , Ratos Wistar , Restrição Física/fisiologia , Restrição Física/psicologia , Maturidade Sexual/efeitos dos fármacos , Maturidade Sexual/fisiologia , Aprendizagem Espacial/efeitos dos fármacos , Estresse Psicológico/metabolismo , Estresse Psicológico/patologia , Estresse Psicológico/psicologia
14.
Subcell Biochem ; 91: 107-122, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30888651

RESUMO

With an increasingly ageing population that is expected to double by 2050 in the U.S., it is paramount that we further understand the neurological changes that occur during ageing. This is relevant not only in the context of "pathological" ageing, where the development of many neurodegenerative disorders is typically a feature of only the older population (and indeed, age is the primary risk factor for many conditions such as Alzheimer's disease), but also for what is considered to be "normal" or "healthy" ageing. Specifically, a significant proportion of the older population are affected by "age-related cognitive decline" (ARCD), which is both independent of dementia and has an incidence 70% higher than dementia alone. However, whilst it is reported that there are pathogenic and phenotypic overlaps between healthy and pathological ageing, it is clear that there is a need to identify the pathways and understand the mechanisms that contribute to this loss of cognitive function with normal ageing, particularly in light of the increasing life expectancy of the global population. Importantly, there is an increasing body of evidence implicating zinc homeostasis as a key player in learning and memory and also potentially ARCD. Further research will ultimately contribute to the development of targeted therapeutics that will promote successful brain ageing. In this chapter we will explore the notion of ARCD, with a perspective on potential key neurochemical pathways that can be targeted for future intervention.


Assuntos
Envelhecimento/fisiologia , Envelhecimento/psicologia , Transtornos Cognitivos/patologia , Transtornos Cognitivos/psicologia , Cognição/fisiologia , Envelhecimento/patologia , Doença de Alzheimer/patologia , Doença de Alzheimer/psicologia , Doença de Alzheimer/terapia , Transtornos Cognitivos/terapia , Humanos , Zinco/metabolismo
15.
J Med Syst ; 43(5): 117, 2019 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-30905048

RESUMO

In order to explore the brain functional and structural imaging results of patients with bipolar disorder and depressive episode without taking medicine, and to further explore the disease mechanism of bipolar disorder by combining with clinical symptoms and cognitive function (neuropsychological test), DPABI (Data Processing and Analysis (Resting-State) For Brain Image) software is used to pre-process fMRI (functional magnetic resonance imaging) data and calculate fALFF (ratio low frequency fluctuation amplitude) index. In addition, SPM8 is applied for grey matter volume analysis based on voxel morphology. Pearson correlation model is used to analyze the relationship between functional and morphological changes and clinical symptoms and cognitive tests. DPABI software and SPSS 22.0 software are used to analyze the data. The results show that corresponding abnormal brain areas are found in both functional and structural aspects of patients with bipolar disorder and depression, involving LCSPT emotional circuits. More importantly, the superior frontal gyrus shows significant abnormalities in both functional and structural analysis.


Assuntos
Transtorno Bipolar/patologia , Transtornos Cognitivos/patologia , Transtorno Depressivo/patologia , Substância Cinzenta/patologia , Processamento de Imagem Assistida por Computador/métodos , Adolescente , Adulto , Grupo com Ancestrais do Continente Asiático , Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/epidemiologia , Encéfalo/patologia , Transtornos Cognitivos/diagnóstico por imagem , Transtornos Cognitivos/epidemiologia , Transtorno Depressivo/diagnóstico por imagem , Transtorno Depressivo/epidemiologia , Escolaridade , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tamanho do Órgão/fisiologia , Adulto Jovem
16.
J Med Syst ; 43(4): 89, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30825011

RESUMO

In order to explore the relationship between hippocampal structure changes and performance symptoms as well as cognitive function in adolescent schizophrenia, taking the brain response signals of psychiatric patients as the research object, the relationship between hippocampal volume drawn by schizophrenia and language memory of negative symptoms is explored based on morphological analysis method. It is found that the left hippocampal volume of schizophrenic patients is abnormal when the whole brain volume is returned, which is significantly lower than that of normal people. It is also found that the left hippocampus volume of schizophrenic patients is a mediator between negative symptoms and speech memory. The results show that the left hippocampus of schizophrenic patients plays an important role in the pathogenesis of schizophrenia.


Assuntos
Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Imagem por Ressonância Magnética/métodos , Memória/fisiologia , Esquizofrenia/patologia , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Criança , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/patologia , Feminino , Humanos , Linguagem , Masculino , Esquizofrenia/epidemiologia , Adulto Jovem
17.
Neurosci Lett ; 703: 11-18, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-30851305

RESUMO

Diabetes related cognitive impairment is a severe complication. The diabetes-induced cognitive impairment is associated with insulin resistance and glucose-induced neuron apoptosis in the brain. We intended to investigate the association of long non-coding RNAs with diabetes-induced cognitive impairment in rats. Here, Type 1diabetes (T1D) rat model was induced using streptozotocin (STZ). The diabetic rats showed significant cognitive dysfunction, with increased latency period to find the hidden platform during morris water maze test. The brain injury and reduced neuronsin STZ-induced diabetic rats was determined using hematoxylin and eosin staining and Nissl's staining. We performed the LncRNA microarray analysis and identified 101 differentially expressed lncRNAs in streptozotocin (STZ)-induced type 1 diabetes (T1D) comparing with control. Among these lncRNA, LOC103690121 was upregulated. in vitro glucose treatment in hippocampal neurons showed LOC103690121 and neuron apoptosis was increased by glucose treatment. Transfection experiments showed LOC103690121 overexpression promoted neuron apoptosis, and its inhibition suppressed glucose-induced apoptosis. Western blot analysis showed that the expression profiles of apoptosis related proteins (cleaved-caspase-3, -8, -9, and Bax) were in line with LOC103690121 expression, while the profiles of Bcl-2 and PI3K/Akt signaling pathway was contrast to LOC103690121 expression. In conclusion, the results of our study confirmed lncRNA LOC103690121 promoted STZ-induced cognitive impairment in diabetic rats by promoting neuron apoptosis through PI3K/Akt signaling pathway.


Assuntos
Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 1/genética , Hipocampo/patologia , Neurônios/patologia , RNA Longo não Codificante/genética , Animais , Apoptose , Proliferação de Células , Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/genética , Transtornos Cognitivos/patologia , Complicações do Diabetes/induzido quimicamente , Complicações do Diabetes/genética , Complicações do Diabetes/patologia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/patologia , Glucose/metabolismo , Glucose/farmacologia , Hipocampo/efeitos dos fármacos , Neurônios/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais , Estreptozocina
18.
Mol Med Rep ; 19(5): 3783-3790, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30864708

RESUMO

Alzheimer's disease (AD) is an irreversible, progressive neurodegenerative disorder of the central nervous system that causes severe cognitive impairment. One of the most significant pathological features of AD is the accumulation of ß­amyloid (Aß) peptide in the brain. Resveratrol (Res) is a polyphenol derived from peanuts, red grapes and other plants, which has received increasing attention due to its neuroprotective features. Tg6799 mice are transgenic mice with five familial AD (FAD) mutations that are also known as 5XFAD mice. The present study aimed to investigate the effects of Res on Tg6799 mice. The transgenic mice were randomly divided into the Res treatment group and the vehicle control group, and were treated with 0.5% Res solution (60 mg/kg) or volume­matched normal saline, respectively. Treatment was administered by oral gavage daily for 60 consecutive days. Res reduced amyloid plaque formation and the levels of Aß42, and ß­secretase 1 levels were also significantly decreased. Furthermore, Res was able to reduce the expression of amyloid precursor protein and its cleavage products. The administration of Res to Tg6799 mice also improved their spatial working memory, as measured by the Y­maze test, and rescued spatial memory deficits, as measured using the Morris water maze test; however, Res did not affect their motor function. In conclusion, this study suggested that Res may reduce Aß­induced neuronal damage, thus preventing memory loss.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Precursor de Proteína beta-Amiloide/fisiologia , Transtornos Cognitivos/prevenção & controle , Modelos Animais de Doenças , Placa Amiloide/prevenção & controle , Presenilina-1/fisiologia , Resveratrol/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Comportamento Animal/efeitos dos fármacos , Transtornos Cognitivos/metabolismo , Transtornos Cognitivos/patologia , Masculino , Transtornos da Memória/metabolismo , Transtornos da Memória/patologia , Transtornos da Memória/prevenção & controle , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Placa Amiloide/metabolismo , Placa Amiloide/patologia
19.
Front Neural Circuits ; 13: 12, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30853901

RESUMO

Prolonged performance of a demanding cognitive task induces cognitive fatigue. We examined the behavioral and neural responses to fatigue-induced cognitive impairments in young and older adults. Particular emphasis was placed on whether the brain exhibited compensatory neural activity in response to cognitive fatigue. High-density EEG was recorded from a young (n = 16; 18-33 years of age) and an older (n = 18; 60-87 years of age) cohort who performed a Stroop task continuously for ∼2 h with no breaks. In the young cohort, behavioral performance declined as the experiment progressed, reflecting the deleterious effects of cognitive fatigue. Neurophysiologically, in addition to declining neural activity as cognitive fatigue developed, there is also evidence of region- and time-specific increase in neural activity, suggesting neural compensation. The compensatory activities followed patterns paralleling that of posterior-anterior shift in aging (PASA) and early to late shift in aging (ELSA) observed in cognitive aging and helped to moderate fatigue-induced behavioral deterioration. In the older cohort, behavioral performance did not decline as the experiment progressed, and neural activity either declined or stayed unchanged, showing no evidence of neural compensation, in contrast to the young. These results suggest that young and older adults coped with cognitive fatigue differently by exhibiting differential responses as a function of time-on-task at both the behavioral level and the neural level.


Assuntos
Envelhecimento/fisiologia , Mapeamento Encefálico , Ondas Encefálicas/fisiologia , Transtornos Cognitivos/patologia , Fadiga/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos Cognitivos/complicações , Sinais (Psicologia) , Eletroencefalografia , Fadiga/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Reação/fisiologia , Teste de Stroop , Adulto Jovem
20.
Eur Radiol ; 29(9): 4937-4947, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30796570

RESUMO

OBJECTIVES: The aims of this study were to examine whether visual MRI rating scales used in diagnostics of cognitive disorders can be estimated computationally and to compare the visual rating scales with their computed counterparts in differential diagnostics. METHODS: A set of volumetry and voxel-based morphometry imaging biomarkers was extracted from T1-weighted and FLAIR images. A regression model was developed for estimating visual rating scale values from a combination of imaging biomarkers. We studied three visual rating scales: medial temporal lobe atrophy (MTA), global cortical atrophy (GCA), and white matter hyperintensities (WMHs) measured by the Fazekas scale. Images and visual ratings from the Amsterdam Dementia Cohort (ADC) (N = 513) were used to develop the models and cross-validate them. The PredictND (N = 672) and ADNI (N = 752) cohorts were used for independent validation to test generalizability. RESULTS: The correlation coefficients between visual and computed rating scale values were 0.83/0.78 (MTA-left), 0.83/0.79 (MTA-right), 0.64/0.64 (GCA), and 0.76/0.75 (Fazekas) in ADC/PredictND cohorts. When performance in differential diagnostics was studied for the main types of dementia, the highest balanced accuracy, 0.75-0.86, was observed for separating different dementias from cognitively normal subjects using computed GCA. The lowest accuracy of about 0.5 for all the visual and computed scales was observed for the differentiation between Alzheimer's disease and frontotemporal lobar degeneration. Computed scales produced higher balanced accuracies than visual scales for MTA and GCA (statistically significant). CONCLUSIONS: MTA, GCA, and WMHs can be reliably estimated automatically helping to provide consistent imaging biomarkers for diagnosing cognitive disorders, even among less experienced readers. KEY POINTS: • Visual rating scales used in diagnostics of cognitive disorders can be estimated computationally from MRI images with intraclass correlations ranging from 0.64 (GCA) to 0.84 (MTA). • Computed scales provided high diagnostic accuracy with single-subject data (area under the receiver operating curve range, 0.84-0.94).


Assuntos
Transtornos Cognitivos/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Idoso , Doença de Alzheimer/diagnóstico por imagem , Atrofia , Biomarcadores , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Transtornos Cognitivos/patologia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA