Aims: Synaptic dysfunction in Parkinson's disease is caused by propagation of pathogenic α-synuclein between neurons. Previously, in multiple system atrophy (MSA), pathologically characterised by ectopic deposition of abnormal α-synuclein predominantly in oligodendrocytes, we demonstrated that the occurrence of memory impairment was associated with the number of α-synuclein-positive neuronal cytoplasmic inclusions (NCIs) in the hippocampus. In the present study, we aimed to investigate how abnormal α-synuclein in the hippocampus can lead to memory impairment.
Methods: We performed pathological and biochemical analyses using a mouse model of adult-onset MSA and human cases (MSA, N = 25; Parkinson's disease, N = 3; Alzheimer's disease, N = 2; normal controls, N = 11). In addition, the MSA model mice were examined behaviourally and physiologically.
Results: In the MSA model, inducible human α-synuclein was first expressed in oligodendrocytes and subsequently accumulated in the cytoplasm of excitatory hippocampal neurons (NCI-like structures) and their presynaptic nerve terminals with the development of memory impairment. α-Synuclein oligomers increased simultaneously in the hippocampus of the MSA model. Hippocampal dendritic spines also decreased in number, followed by suppression of long-term potentiation. Consistent with these findings obtained in the MSA model, post-mortem analysis of human MSA brain tissues showed that cases of MSA with memory impairment developed more NCIs in excitatory hippocampal neurons along with α-synuclein oligomers than those without.
Conclusions: Our results provide new insights into the role of α-synuclein oligomers as a possible pathological cause of memory impairment in MSA.
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http://dx.doi.org/10.1111/nan.12844 | DOI Listing |
Psychopharmacology (Berl)
December 2024
Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, Kings College London, De Crespigny Park, London, SE5 8AF, UK.
Rationale: Working memory impairment is a prominent feature of schizophrenia which predicts clinical and functional outcomes. Preclinical data suggest histamine-3 receptor (H3R) expression in cortical pyramidal neurons may have a role in working memory, and post-mortem data has found disruptions of H3R expression in schizophrenia.
Objectives: We examined the role of H3R in vivo to elucidate its role on working memory impairment in schizophrenia.
Brain Res
December 2024
Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Departamento de Ciências Morfológicas, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Congenital Zika Syndrome (CZS) is a condition that arises when a neonate presents with abnormalities resulting from Zika virus infection during gestation. While microcephaly is a prominent feature of the syndrome, other forms of brain damage are also observed, often accompanied by significant neurological complications. It is therefore essential to investigate the long-term effects of CZS, with special attention to sex differences, particularly concerning hippocampal function, given its vulnerability to viral infections.
View Article and Find Full Text PDFMagn Reson Imaging
December 2024
Department of Neurology, Yichang Central People's Hospital, The First College of Clinical Medical Science, China Three Gorges University, Yichang, China. Electronic address:
Introduction: More and more evidence suggesting that internal carotid artery stenosis is not only a risk factor for ischemic stroke but also for cognitive impairments. Hypoperfusion and silent micro emboli have been reported as the pathophysiological mechanisms causing cognitive impairment. The effect of carotid artery stenting (CAS) on cognitive function varied from study to study.
View Article and Find Full Text PDFArch Clin Neuropsychol
December 2024
Department of Psychology, University of Saskatchewan, 9 Campus Drive, Saskatoon, SK, S7N 5A5, Canada.
Objective: Technology can be combined with psychological interventions to support older adults with memory concerns. Using a bi-phasic design, cognitive rehabilitation (CR) was integrated with off-the-shelf technology and delivered to two people with cognitive impairment, and one care partner.
Method: Pre- and post-intervention assessments were completed for all participants.
Epilepsy Behav
December 2024
Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye.
Electrical status epilepticus in sleep (ESES) is an electrographic pattern associated with cognitive impairment. Our study aimed to prospectively evaluate the psychiatric findings and language skills in patients diagnosed with ESES and to determine the immune modulatory treatment-responsive subgroups. We assessed the patients for psychiatric features and language skills at the baseline and 12 months after.
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