scholarly journals Synaptic tau: A pathological or physiological phenomenon?

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Miranda Robbins ◽  
Emma Clayton ◽  
Gabriele S. Kaminski Schierle
Keyword(s):  
Neurofibrillary Tangles ◽  
Declarative Memory ◽  
Synaptic Function ◽  
Current Evidence ◽  
Tau Pathology ◽  
Research Focus ◽  
Synaptic Loss ◽  
Physiological Phenomenon ◽  
Synaptic Pathology

AbstractIn this review, we discuss the synaptic aspects of Tau pathology occurring during Alzheimer’s disease (AD) and how this may relate to memory impairment, a major hallmark of AD. Whilst the clinical diagnosis of AD patients is a loss of working memory and long-term declarative memory, the histological diagnosis is the presence of neurofibrillary tangles of hyperphosphorylated Tau and Amyloid-beta plaques. Tau pathology spreads through synaptically connected neurons to impair synaptic function preceding the formation of neurofibrillary tangles, synaptic loss, axonal retraction and cell death. Alongside synaptic pathology, recent data suggest that Tau has physiological roles in the pre- or post- synaptic compartments. Thus, we have seen a shift in the research focus from Tau as a microtubule-stabilising protein in axons, to Tau as a synaptic protein with roles in accelerating spine formation, dendritic elongation, and in synaptic plasticity coordinating memory pathways. We collate here the myriad of emerging interactions and physiological roles of synaptic Tau, and discuss the current evidence that synaptic Tau contributes to pathology in AD.

scholarly journals Synaptic plasticity in multiple sclerosis and in experimental autoimmune encephalomyelitis

2014 ◽  
Vol 369 (1633) ◽  
pp. 20130162 ◽  
Author(s):  
Robert Nisticò ◽  
Francesco Mori ◽  
Marco Feligioni ◽  
Ferdinando Nicoletti ◽  
Diego Centonze
Keyword(s):  
Multiple Sclerosis ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Long Term Potentiation ◽  
Synaptic Function ◽  
Autoimmune Encephalomyelitis ◽  
Term Potentiation ◽  
Synaptic Pathology ◽  
New Treatments ◽  
Experimental Autoimmune

Approximately half of all patients with multiple sclerosis (MS) experience cognitive dysfunction, including learning and memory impairment. Recent studies suggest that hippocampal pathology is involved, although the mechanisms underlying these deficits remain poorly understood. Evidence obtained from a mouse model of MS, the experimental autoimmune encephalomyelitis (EAE), suggests that in the hippocampus of EAE mice long-term potentiation (LTP) is favoured over long-term depression in response to repetitive synaptic activation, through a mechanism dependent on enhanced IL-1β released from infiltrating lymphocytes or activated microglia. Facilitated LTP during an immune-mediated attack might underlie functional recovery, but also cognitive deficits and excitotoxic neurodegeneration. Having identified that pro-inflammatory cytokines such as IL-1β can influence synaptic function and integrity in early MS, it is hoped that new treatments targeted towards preventing synaptic pathology can be developed.

scholarly journals In vivo tau pathology is associated with synaptic loss and altered synaptic function

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Emma M. Coomans ◽  
Deborah N. Schoonhoven ◽  
Hayel Tuncel ◽  
Sander C. J. Verfaillie ◽  
Emma E. Wolters ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synaptic Function ◽  
Oscillatory Activity ◽  
Binding Potential ◽  
Alpha Power ◽  
Spectral Measures ◽  
Tau Pathology ◽  
Synaptic Loss ◽  
Synaptic Density

Abstract Background The mechanism of synaptic loss in Alzheimer’s disease is poorly understood and may be associated with tau pathology. In this combined positron emission tomography (PET) and magnetoencephalography (MEG) study, we aimed to investigate spatial associations between regional tau pathology ([18F]flortaucipir PET), synaptic density (synaptic vesicle 2A [11C]UCB-J PET) and synaptic function (MEG) in Alzheimer’s disease. Methods Seven amyloid-positive Alzheimer’s disease subjects from the Amsterdam Dementia Cohort underwent dynamic 130-min [18F]flortaucipir PET, dynamic 60-min [11C]UCB-J PET with arterial sampling and 2 × 5-min resting-state MEG measurement. [18F]flortaucipir- and [11C]UCB-J-specific binding (binding potential, BPND) and MEG spectral measures (relative delta, theta and alpha power; broadband power; and peak frequency) were assessed in cortical brain regions of interest. Associations between regional [18F]flortaucipir BPND, [11C]UCB-J BPND and MEG spectral measures were assessed using Spearman correlations and generalized estimating equation models. Results Across subjects, higher regional [18F]flortaucipir uptake was associated with lower [11C]UCB-J uptake. Within subjects, the association between [11C]UCB-J and [18F]flortaucipir depended on within-subject neocortical tau load; negative associations were observed when neocortical tau load was high, gradually changing into opposite patterns with decreasing neocortical tau burden. Both higher [18F]flortaucipir and lower [11C]UCB-J uptake were associated with altered synaptic function, indicative of slowing of oscillatory activity, most pronounced in the occipital lobe. Conclusions These results indicate that in Alzheimer’s disease, tau pathology is closely associated with reduced synaptic density and synaptic dysfunction.

Mechanism of Intermittent Theta-Burst Stimulation in Synaptic Pathology in the Prefrontal Cortex in an Antidepressant-Resistant Depression Rat Model

2020 ◽  
Vol 31 (1) ◽  
pp. 575-590
Author(s):  
Chi-Wei Lee ◽  
Han-Fang Wu ◽  
Ming-Chia Chu ◽  
Yueh-Jung Chung ◽  
Wei-Chang Mao ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Rat Model ◽  
Synaptic Function ◽  
Theta Burst Stimulation ◽  
Burst Stimulation ◽  
Long Term Depression ◽  
Synaptic Pathology ◽  
Resistant Depression ◽  
Theta Burst

Abstract Intermittent theta-burst stimulation (iTBS), a form of repetitive transcranial magnetic stimulation, is considered a potential therapy for treatment-resistant depression. The synaptic mechanism of iTBS has long been known to be an effective method to induce long-term potentiation (LTP)-like plasticity in humans. However, there is limited evidence as to whether the antidepressant effect of iTBS is associated with change in synaptic function in the prefrontal cortex (PFC) in preclinical study. Hence, we applied an antidepressant (i.e., fluoxetine)-resistant depression rat model induced by severe foot-shocks to investigate the antidepressant efficacy of iTBS in the synaptic pathology. The results showed that iTBS treatment improved not only the impaired LTP, but also the aberrant long-term depression in the PFC of antidepressant-resistant depression model rats. Moreover, the mechanism of LTP improvement by iTBS involved downstream molecules of brain-derived neurotrophic factor, while the mechanism of long-term depression improvement by iTBS involved downstream molecules of proBDNF. The aberrant spine morphology was also improved by iTBS treatment. This study demonstrated that the mechanism of the iTBS paradigm is complex and may regulate not only excitatory but also inhibitory synaptic effects in the PFC.

Effect of sleep on memory for binding different types of visual information

2020 ◽  
Author(s):  
John J Shaw ◽  
Zhisen Urgolites ◽  
Padraic Monaghan
Keyword(s):  
Visual Information ◽  
Storage Capacity ◽  
Declarative Memory ◽  
Recognition Task ◽  
Forced Choice ◽  
Long Term Memory ◽  
Term Memory ◽  
Different Types ◽  
Types Of Information

Visual long-term memory has a large and detailed storage capacity for individual scenes, objects, and actions. However, memory for combinations of actions and scenes is poorer, suggesting difficulty in binding this information together. Sleep can enhance declarative memory of information, but whether sleep can also boost memory for binding information and whether the effect is general across different types of information is not yet known. Experiments 1 to 3 tested effects of sleep on binding actions and scenes, and Experiments 4 and 5 tested binding of objects and scenes. Participants viewed composites and were tested 12-hours later after a delay consisting of sleep (9pm-9am) or wake (9am-9pm), on an alternative forced choice recognition task. For action-scene composites, memory was relatively poor with no significant effect of sleep. For object-scene composites sleep did improve memory. Sleep can promote binding in memory, depending on the type of information to be combined.

«Благочестивые путешествия» в Иерусалим: российские паломники-писатели XVIII столетия

2019 ◽  
Author(s):  
S.A. Kirillina
Keyword(s):  
Travel Literature ◽  
Religious Affiliation ◽  
Russian Literature ◽  
Social Background ◽  
Cultural Significance ◽  
Research Focus ◽  
Russian Orthodoxy ◽  
Ottoman History ◽  
Holy Places

Abstract The culmination of long-term development of the traditional pilgrimage genre in Russian literature falls on the eighteenth century. Reports of Russian pilgrims to the Christian Holy Places of the Middle East produced during this period, not only precede the nineteenth century the Golden age of travel literature in Russia, but also retain their great historical and cultural significance and still remain a subject of research for scholars dwelling on the Arab-Ottoman history. The authors attention is focused on 12 pilgrims accounts written by Ivan Lukjanov (dates of travel: 17011703), Makariy and Seliverst (17041707), Andrey Ignatiev (17071708), Ippolit Vishenskiy (17071709), Varlaam (17121714), Matvey Nechaev (17211722), Sylvester and Nicodim (1722), Vasiliy Grigorowich-Barskiy (17231747), Serapion (17491751), Ignatiy Denshin (17661776), Leontiy (17631765) and Meletiy (17931794). The research focus of the article is on the personalities of the pilgrimagewriters, their biographical data and social background as well as the fates of their writings after their completion. Some of the pilgrims accounts received due credit long after they had been produced, others gained great popularity at the time of writing and some of them were almost forgotten and mostly neglected by scholars of the following generations. The article also deals with the religious affiliation of the pilgrimage-writers, which predetermined their perception of the Arab-Ottoman world through the prism of Russian Orthodoxy and the values preached by this particular brand of Christianity.Аннотация В XVIII в. традиционный паломнический жанр в русской словесности достиг подлинного расцвета и подошел к своему логическому завершению. Паломнические описания Святой Земли, составленные в XVIII в., не только предваряют XIX столетие золотой век путешествий в русской литературе, но и сохраняют свою самостоятельную историко-культурную значимость, а их содержательная сторона продолжает оставаться объектом исследований ученых, в том числе арабистов и османистов. Внимание автора сосредоточено на 12 паломнических описаниях, авторство которых принадлежит Ивану Лукьянову (даты путешествия: 17011703 гг.), Макарию и Селиверсту (17041707 гг.), Андрею Игнатьеву (17071708 гг.), Ипполиту Вишенскому (17071709 гг.), Варлааму (17121714 гг.), Матвею Нечаеву (17211722 гг.), Сильвестру и Никодиму (1722 г.), Василию Григоровичу-Барскому (17231747 гг.), Серапиону (17491751 гг.), Игнатию Деншину (17661776 гг.), Леонтию (17631765 гг.) и Мелетию (17931794 гг.). В исследовательском фокусе статьи находятся личности паломников и дошедшие до нас сведения об их биографиях, их социальное происхождение, а также последующая судьба их произведений. Одни письменные свидетельства богомольцев о хождениях к святым местам Ближнего Востока завоевали признание современников, другие были по достоинству оценены значительно позднее, а некоторые практически выпали из поля зрения последующих поколений исследователей. В статье также отдельно рассмотрена конфессиональная принадлежность паломников-писателей, которая предопределила их восприятие арабо-османского мира сквозь призму Русского Православия.

Integrated Biomarkers for Depression in Alzheimer’s Disease: A Critical Review

2017 ◽  
Vol 14 (4) ◽  
pp. 441-452 ◽  
Author(s):  
Sofia Wenzler ◽  
Christian Knochel ◽  
Ceylan Balaban ◽  
Dominik Kraft ◽  
Juliane Kopf ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Affect Regulation ◽  
Current Evidence ◽  
Diagnostic Process ◽  
Neuropsychiatric Manifestation ◽  
The Brain ◽  
Control Functional

Depression is a common neuropsychiatric manifestation among Alzheimer’s disease (AD) patients. It may compromise everyday activities and lead to a faster cognitive decline as well as worse quality of life. The identification of promising biomarkers may therefore help to timely initiate and improve the treatment of preclinical and clinical states of AD, and to improve the long-term functional outcome. In this narrative review, we report studies that investigated biomarkers for AD-related depression. Genetic findings state AD-related depression as a rather complex, multifactorial trait with relevant environmental and inherited contributors. However, one specific set of genes, the brain derived neurotrophic factor (BDNF), specifically the Val66Met polymorphism, may play a crucial role in AD-related depression. Regarding neuroimaging markers, the most promising findings reveal structural impairments in the cortico-subcortical networks that are related to affect regulation and reward / aversion control. Functional imaging studies reveal abnormalities in predominantly frontal and temporal regions. Furthermore, CSF based biomarkers are seen as potentially promising for the diagnostic process showing abnormalities in metabolic pathways that contribute to AD-related depression. However, there is a need for standardization of methodological issues and for replication of current evidence with larger cohorts and prospective studies.

Acute and chronic synaptic pathology in multiple sclerosis gray matter

2021 ◽  
pp. 135245852110221
Author(s):  
Marco Vercellino ◽  
Stella Marasciulo ◽  
Silvia Grifoni ◽  
Elena Vallino-Costassa ◽  
Chiara Bosa ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Brain Tissue ◽  
Gray Matter ◽  
Axonal Loss ◽  
Strong Indication ◽  
Synaptic Loss ◽  
Synaptic Density ◽  
Synaptic Pathology ◽  
Gabaergic Synapses ◽  
And Control

Objectives: To investigate the extent of synaptic loss, and the contribution of gray matter (GM) inflammation and demyelination to synaptic loss, in multiple sclerosis (MS) brain tissue. Methods: This study was performed on two different post-mortem series of MS and control brains, including deep GM and cortical GM. MS brain samples had been specifically selected for the presence of active demyelinating GM lesions. Over 1,000,000 individual synapses were identified and counted using confocal microscopy, and further characterized as glutamatergic/GABAergic. Synaptic counts were also correlated with neuronal/axonal loss. Results: Important synaptic loss was observed in active demyelinating GM lesions (−58.9%), while in chronic inactive GM lesions, synaptic density was only mildly reduced compared to adjacent non-lesional gray matter (NLGM) (−12.6%). Synaptic loss equally affected glutamatergic and GABAergic synapses. Diffuse synaptic loss was observed in MS NLGM compared to control GM (−21.2% overall). Conclusion: This study provides evidence, in MS brain tissue, of acute synaptic damage/loss during active GM inflammatory demyelination and of synaptic reorganization in chronically demyelinated GM, affecting equally glutamatergic and GABAergic synapses. Furthermore, this study provides a strong indication of widespread synaptic loss in MS NLGM also independently from focal GM demyelination.

Cerebrovascular and Neurodegenerative Pathologies in Long-Term Stable Mild Cognitive Impairment

2021 ◽  
pp. 1-15
Author(s):  
Manu J. Sharma ◽  
Brandy L. Callahan
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cerebral Amyloid Angiopathy ◽  
Neurofibrillary Tangles ◽  
Small Vessel Disease ◽  
Significant Proportion ◽  
Amyloid Angiopathy ◽  
Prodromal Phase ◽  
Cerebral Amyloid

Background: Mild cognitive impairment (MCI) is considered by some to be a prodromal phase of a progressive disease (i.e., neurodegeneration) resulting in dementia; however, a substantial portion of individuals (ranging from 5–30%) remain cognitively stable over the long term (sMCI). The etiology of sMCI is unclear but may be linked to cerebrovascular disease (CVD), as evidence from longitudinal studies suggest a significant proportion of individuals with vasculopathy remain stable over time. Objective: To quantify the presence of neurodegenerative and vascular pathologies in individuals with long-term (>5-year) sMCI, in a preliminary test of the hypothesis that CVD may be a contributor to non-degenerative cognitive impairment. We expect frequent vasculopathy at autopsy in sMCI relative to neurodegenerative disease, and relative to individuals who convert to dementia. Methods: In this retrospective study, using data from the National Alzheimer’s Coordinating Center, individuals with sMCI (n = 28) were compared to those with MCI who declined over a 5 to 9-year period (dMCI; n = 139) on measures of neurodegenerative pathology (i.e., Aβ plaques, neurofibrillary tangles, TDP-43, and cerebral amyloid angiopathy) and CVD (infarcts, lacunes, microinfarcts, hemorrhages, and microbleeds). Results: Alzheimer’s disease pathology (Aβ plaques, neurofibrillary tangles, and cerebral amyloid angiopathy) was significantly higher in the dMCI group than the sMCI group. Microinfarcts were the only vasculopathy associated with group membership; these were more frequent in sMCI. Conclusion: The most frequent neuropathology in this sample of long-term sMCI was microinfarcts, tentatively suggesting that silent small vessel disease may characterize non-worsening cognitive impairment.

scholarly journals Adhesive Small Bowel Obstruction and the six w’s: Who, How, Why, When, What, and Where to diagnose and operate?

2021 ◽  
pp. 145749692098276
Author(s):  
M. Podda ◽  
M. Khan ◽  
S. Di Saverio
Keyword(s):  
Small Bowel ◽  
Small Bowel Obstruction ◽  
Bowel Obstruction ◽  
Conservative Management ◽  
Bowel Ischemia ◽  
Current Evidence ◽  
First Episode ◽  
Adhesive Small Bowel Obstruction ◽  
Highly Effective

Background and Aims: Approximately 75% of patients admitted with small bowel obstruction have intra-abdominal adhesions as their cause (adhesive small bowel obstruction). Up to 70% of adhesive small bowel obstruction cases, in the absence of strangulation and bowel ischemia, can be successfully treated with conservative management. However, emerging evidence shows that surgery performed early during the first episode of adhesive small bowel obstruction is highly effective. The objective of this narrative review is to summarize the current evidence on adhesive small bowel obstruction management strategies. Materials and Methods: A review of the literature published over the last 20 years was performed to assess Who, hoW, Why, When, What, and Where diagnose and operate on patients with adhesive small bowel obstruction. Results: Adequate patient selection through physical examination and computed tomography is the key factor of the entire management strategy, as failure to detect patients with strangulated adhesive small bowel obstruction and bowel ischemia is associated with significant morbidity and mortality. The indication for surgical exploration is usually defined as a failure to pass contrast into the ascending colon within 8–24 h. However, operative management with early adhesiolysis, defined as operative intervention on either the calendar day of admission or the calendar day after admission, has recently shown to be associated with an overall long-term survival benefit compared to conservative management. Regarding the surgical technique, laparoscopy should be used only in selected patients with an anticipated single obstructing band, and there should be a low threshold for conversion to an open procedure in cases of high risk of bowel injuries. Conclusion: Although most adhesive small bowel obstruction patients without suspicion of bowel strangulation or gangrene are currently managed nonoperatively, the long-term outcomes following this approach need to be analyzed in a more exhaustive way, as surgery performed early during the first episode of adhesive small bowel obstruction has shown to be highly effective, with a lower rate of recurrence.

scholarly journals Determinants of Outcomes of Acute Kidney Injury: Clinical Predictors and Beyond

2021 ◽  
Vol 10 (6) ◽  
pp. 1175
Author(s):  
Emaad M. Abdel-Rahman ◽  
Faruk Turgut ◽  
Jitendra K. Gautam ◽  
Samir C. Gautam
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Kidney Injury ◽  
Complete Recovery ◽  
Severe Form ◽  
Clinical Syndrome ◽  
Current Evidence ◽  
Clinical Predictors ◽  
End Stage

Acute kidney injury (AKI) is a common clinical syndrome characterized by rapid impairment of kidney function. The incidence of AKI and its severe form AKI requiring dialysis (AKI-D) has been increasing over the years. AKI etiology may be multifactorial and is substantially associated with increased morbidity and mortality. The outcome of AKI-D can vary from partial or complete recovery to transitioning to chronic kidney disease, end stage kidney disease, or even death. Predicting outcomes of patients with AKI is crucial as it may allow clinicians to guide policy regarding adequate management of this problem and offer the best long-term options to their patients in advance. In this manuscript, we will review the current evidence regarding the determinants of AKI outcomes, focusing on AKI-D.

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