Dataset Information

Neural Stem Cells Rescue Cognitive and Motor Dysfunction in a Transgenic Model of Dementia with Lewy Bodies through a BDNF-Dependent Mechanism.

ABSTRACT: Accumulation of ?-synuclein (?-syn) into insoluble aggregates occurs in several related disorders collectively referred to as synucleinopathies. To date, studies have used neural stem cells (NSCs) to examine questions about ?-syn propagation, but have overlooked the therapeutic potential of NSC transplantation to modulate cognition in disorders such as dementia with Lewy bodies or Parkinson's disease dementia. Here, we show that striatal transplantation of NSCs into aged ?-syn transgenic mice significantly improves performance in multiple cognitive and motor domains. This recovery is associated with NSC expression of brain-derived neurotrophic factor (BDNF), which restores depleted levels and modulates dopaminergic and glutamatergic systems. Most importantly, transplantation of BDNF-depleted NSCs fails to improve behavior, whereas AAV-mediated BDNF delivery mimics the benefits of NSC transplantation, supporting a critical role for this neurotrophin in functional improvement. Thus, NSC transplantation could offer a promising approach to treat the understudied yet devastating cognitive components of many synucleinopathies.

SUBMITTER: Goldberg NRS

PROVIDER: S-EPMC4649255 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Neural Stem Cells Rescue Cognitive and Motor Dysfunction in a Transgenic Model of Dementia with Lewy Bodies through a BDNF-Dependent Mechanism.

Goldberg Natalie R S NRS Caesar Jacqueline J Park Ashley A Sedgh Shawn S Finogenov Gilana G Masliah Eliezer E Davis Joy J Blurton-Jones Mathew M

Stem cell reports 20151017 5

Accumulation of α-synuclein (α-syn) into insoluble aggregates occurs in several related disorders collectively referred to as synucleinopathies. To date, studies have used neural stem cells (NSCs) to examine questions about α-syn propagation, but have overlooked the therapeutic potential of NSC transplantation to modulate cognition in disorders such as dementia with Lewy bodies or Parkinson's disease dementia. Here, we show that striatal transplantation of NSCs into aged α-syn transgenic mice si ...[more]

PMID: 26489892

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Project description:Objective: Characteristic parkinsonism is the major comorbidity of dementia with Lewy bodies (DLB). We aimed to differentiate DLB from Alzheimer's disease (AD) with motor dysfunction using a composite scale with a characteristic motor dysfunction questionnaire (MDQ) and dopamine transporter (DAT) imaging. It could help detect DLB easily in healthcare settings without movement disorder specialists. Methods: This is a two-phase study. In the design phase, seven questions were selected and composed of a novel MDQ. In the test phase, all participants with DLB, AD, or non-dementia (ND) control completed dementia and parkinsonism survey, the novel designed questionnaire, DAT imaging, and composite scales of MDQ and DAT. The cutoff scores of the MDQ, semiquantitative analysis of the striatal-background ratio (SBR) and visual rating of DAT, and the composite scale of MDQ and DAT for discriminating DLB from AD or ND were derived and compared. Results: A total of 277 participants were included in this study (126 with DLB, 86 with AD, and 65 with ND). Compared with the AD or ND groups, the DLB group showed a significantly higher frequency in all seven items in the MDQ and a significantly lower SBR. For discrimination of DLB from non-DLB with MDQ, SBR, and composite scale, the cutoff scores of 3/2, 1.37/1.38, and 6/5 were suggested for the diagnosis of DLB with the sensitivities/specificities of 0.91/0.72, 0.91/0.80, and 0.87/0.93, respectively. The composite scale significantly improved the accuracy of discrimination compared with either the MDQ or SBR. Conclusion: This study showed that the novel designed simple questionnaire was a practical screening tool and had similar power to DAT scanning to detect DLB. The questionnaire can be applied in clinical practice and population studies for screening DLB. In addition, the composite scale of MDQ and DAT imaging further improved the diagnostic accuracy, indicating the superiority of the dual-model diagnostic tool.

Project description:Swallowing dysfunction is an increasingly recognized problem in patients with dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), which can result in aspiration pneumonia and death. Few studies have examined potential ways of improving swallowing function in this fragile patient group. The aim of this study was to evaluate swallowing dysfunction and carbonated liquid using videofluoroscopy in DLB and PDD patients.A total of 48 patients with DLB and PDD were referred for a clinical examination with videofluoroscopy. Descriptive overall assessments were provided at the time of the examination regarding swallowing function and the effects of different modifications, including carbonated thin liquid (CTL). Additionally, a repeated measures quantitative retrospective analysis has been performed comparing 1) thin liquids; 2) thickened liquids and 3) CTLs, with regard to the quantitative variables 1) pharyngeal transit time (PTT); 2) pharyngeal retention and 3) tracheal penetration.In all, 40/48 (83%) of the patients had a swallowing dysfunction, which was confirmed on videofluoroscopy, with 34/40 (85%) patients having a pharyngeal-type dysfunction. A total of 14/40 (35%) patients with an objective swallowing impairment did not have any subjective swallowing symptoms. Out of the patients with swallowing dysfunction, 87% had an overall improved swallowing function with carbonated liquid. PTT for carbonated liquid (median 633 ms, interquartile range [IQR] 516-786 ms) was quicker than for thin liquid (760 ms, IQR 613-940 ms, P=0.014) and thickened liquid (880.0 ms, IQR 600-1,500 ms, P<0.001). No significant effect was seen in residue or penetration.The majority of patients with DLB or PDD had a swallowing dysfunction, sometimes without subjective swallowing symptoms, which improved with carbonated liquid. This highlights the importance of investigating patients with videofluoroscopy and to carry out a prospective interventional study to further evaluate carbonated liquid, also addressing the effects on quality of life, aspiration and mortality.

Dataset Information

Neural Stem Cells Rescue Cognitive and Motor Dysfunction in a Transgenic Model of Dementia with Lewy Bodies through a BDNF-Dependent Mechanism.

Publications

Neural Stem Cells Rescue Cognitive and Motor Dysfunction in a Transgenic Model of Dementia with Lewy Bodies through a BDNF-Dependent Mechanism.

Similar Datasets

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