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In Vivo Imaging of Anterograde and Retrograde Axonal Transport in Rodent Peripheral Nerves.

Axonal transport, which is the process mediating the active shuttling of a variety cargoes from one end of an axon to the other, is essential for the development, function, and survival of neurons. Impairments in this dynamic process are linked to diverse nervous system diseases and advanced ageing. It is thus essential that we quantitatively study the kinetics of axonal transport to gain an improved understanding of neuropathology as well as the molecular and cellular mechanisms regulating cargo trafficking. One of the best ways to achieve this goal is by imaging individual, fluorescent cargo…

P301 L, an FTDP-17 Mutant, Exhibits Enhanced Glycation in vitro.

BACKGROUND: Frontotemporal dementia and parkinsonism-linked to chromosome-17 are a group of diseases with tau mutations leading to primary tauopathies which include progressive supranuclear palsy, corticobasal syndrome, and frontotemporal lobar degeneration. Alzheimer's disease is a non-primary tauopathy, which displays tau neuropathology of excess tangle formation and accumulation. FTDP-17 mutations are responsible for early onset of AD, which can be attributed to compromised physiological functions due to the mutations. Tau is a microtubule-binding protein that secures the integrity of polym…

Inhibition of sphingolipid synthesis improves outcomes and survival in GARP mutant wobbler mice, a model of motor neuron degeneration.

Numerous mutations that impair retrograde membrane trafficking between endosomes and the Golgi apparatus lead to neurodegenerative diseases. … nic treatment of wobbler mice with myriocin markedly improved their wellness scores, grip strength, neuropathology, and survival. Proteomic analyses of wobbler fibroblasts revealed extensive missorting of lysosomal proteins, including sphingolipid catabolism enzymes, to the Golgi compartment, which may contribute to the sphingolipid abnormalities. Our findings e …

Identification of Novel Alzheimer's Disease Loci Using Sex-Specific Family-Based Association Analysis of Whole-Genome Sequence Data.

With the advent of whole genome-sequencing (WGS) studies, family-based designs enable sex-specific analysis approaches that can be applied t … onal repressor of membrane metalloproteases (MMP). Members of this MMP family were implicated in AD neuropathology.

Acid Ceramidase Depletion Impairs Neuronal Survival and Induces Morphological Defects in Neurites Associated with Altered Gene Transcription and Sphingolipid Content.

The ASAH1 gene encodes acid ceramidase (AC), an enzyme that is implicated in the metabolism of ceramide (Cer). Mutations in the ASAH1 gene c … udy shows the critical role of AC in neurons and suggests how AC depletion leads to defects seen in neuropathology of SMA-PME and FD.

Periventricular White Matter Alterations From Explosive Blast in a Large Animal Model: Mild Traumatic Brain Injury or "Subconcussive" Injury?

The neuropathology of mild traumatic brain injury in humans resulting from exposure to explosive blast is poorly understood as this condition is rarely fatal. A large animal model may better reflect the injury patterns in humans. We investigated the effect of explosive blasts on the constrained head minimizing the effects of whole head motion. Anesthetized Yucatan minipigs, with body and head restrained, were placed in a 3-walled test structure and exposed to 1, 2, or 3 explosive blast shock waves of the same intensity. Axonal injury was studied 3 weeks to 8 months postblast using β-amyloid pr…

Variability and sex-dependence of hypothermic neuroprotection in a rat model of neonatal hypoxic-ischaemic brain injury: a single laboratory meta-analysis.

Therapeutic hypothermia (HT) is standard care for term infants with hypoxic-ischaemic (HI) encephalopathy. However, the efficacy of HT in pr … the median injury in each group within each litter (n = 277, 44.5%) were also analysed using formal neuropathology, which showed neuroprotection by HT throughout the brain, particularly in females. Our results suggest an inherent variability and sex-dependence of the neuroprotective response to HT, with the majority of studies in the Vannucci model vastly underp …

Early-Onset Dementia in War Veterans: Brain Polypathology and Clinicopathologic Complexity.

The neuropathology associated with cognitive decline in military personnel exposed to traumatic brain injury (TBI) and chronic stress is incompletely understood. Few studies have examined clinicopathologic correlations between phosphorylated-tau neurofibrillary tangles, β-amyloid neuritic plaques, neuroinflammation, or white matter (WM) lesions, and neuropsychiatric disorders in veterans. We describe clinicopathologic findings in 4 military veterans with early-onset dementia (EOD) who had varying histories of blunt- and blast-TBI, cognitive decline, behavioral abnormalities, post-traumatic str…

Structural imaging of the retina in psychosis spectrum disorders: current status and perspectives.

PURPOSE OF REVIEW: Structural changes of the retina in schizophrenia and other psychotic disorders seem plausible as these conditions are ac … date the nature and timing of developmental, progressive, inflammatory, and degenerative aspects of neuropathology and pathophysiology, and to assist with characterizing heterogeneity and facilitating personalized treatment approaches.

The Lactate Receptor HCA1 Is Present in the Choroid Plexus, the Tela Choroidea, and the Neuroepithelial Lining of the Dorsal Part of the Third Ventricle.

The volume, composition, and movement of the cerebrospinal fluid (CSF) are important for brain physiology, pathology, and diagnostics. Never … the ability to respond to alterations in CSF lactate in body-brain signaling, but also as a sign of neuropathology (e.g., stroke and Alzheimer's disease biomarker).

Оценка концентраций цереброспинной жидкости CXCL13 и подмножеств лимфоцитов в переносимом клещей энцефалите.

ЦЕЛИ: Недавние исследования свидетельствуют о том, что клиническое представление переносимого клещей энцефалита (ТБЭ) определяется иммунной реакцией принимающей стороны на вирус энцефалита (ТБЭВ). Цель этого исследования состояла в том, чтобы охарактеризовать иммунную реакцию в БТО, с тем чтобы лучше понять иммунопатогенез этой болезни. МЕТОДЫ: Уровни антиТБЭВ антитела, цереброспинная жидкость (CSF) и популяции лимфоидов в крови, а также концентрации CXCL13 (эффективный химиопатоген B и T-клеток) были проанализированы у 35 пациентов с ТБВ (20 взрослых и 15 детей).Результаты: По сравнению с кро

Совпадение в аннотации оригинала
OBJECTIVES: Recent studies suggest that the clinical presentation of tick-borne encephalitis (TBE) is determined by the host immune response … CONCLUSIONS: CD4+ cells are abundant in the CSF of patients with TBE. CXCL13 may be involved in the neuropathology of TBE by attracting different subsets of lymphocytes to the CSF.

Neuroinflammation disorders exacerbated by environmental stressors.

Neuroinflammation is a condition characterized by the elaboration of proinflammatory mediators within the central nervous system. Neuroinfla … es chronic sickness behavior disorders can occur in the absence of an underlying cause or attendant neuropathology. Here, we review myalgic enchepalomyelitis/chronic fatigue syndrome (ME/CFS), Gulf War Illness (GWI), and chemobrain as examples of such disorders and propose that they can be exacerbated and perhaps initiated by a variety of environmental stressors …

High frequency repetitive transcranial magnetic stimulation of supplementary motor cortex for obsessive compulsive disorder.

Obsessive compulsive disorder (OCD) is a common psychiatric disorder that can lead to significant dysfunction. It is treated with medications and or cognitive behavior therapy. Many patients with OCD do not respond to above mentioned conventional treatments. OCD is also a disorder with well delineated neuropathology in brain areas that form cortico-striato-thalamocortical loop. Transcranial magnetic stimulation (TMS) can not only offer a noninvasive treatment modality for many of these patients but can also specifically and beneficially affect involved neuronal areas. TMS stimulation of variou…

Pressure Reveals Unique Conformational Features in Prion Protein Fibril Diversity.

The prion protein (PrP) misfolds and assembles into a wide spectrum of self-propagating quaternary structures, designated PrPSc. These various PrP superstructures can be functionally different, conferring clinically distinctive symptomatology, neuropathology and infectious character to the associated prion diseases. However, a satisfying molecular basis of PrP structural diversity is lacking in the literature. To provide mechanistic insights into the etiology of PrP polymorphism, we have engineered a set of 6 variants of the human protein and obtained PrP amyloid fibrils. We show that pressure…

Neurotransmitter Imbalance in the Brain and Alzheimer's Disease Pathology.

BACKGROUND: Cholinesterase inhibitors represent three of the four treatments for Alzheimer's disease (AD), and target the pathological reduc … s, AD, and 'asymptomatic AD' (ASYMAD), i.e., cognitively normal individuals that had significant AD neuropathology. Three brain areas were studied, the middle frontal gyrus (MFG), the inferior temporal gyrus (ITG), and the cerebellum. RESULTS: 12 of 15 metabolites involved in neurotransmitter metabolism were shown to be associated with AD pathology. Decreases i …

Insight Into the Emerging Role of Striatal Neurotransmitters in the Pathophysiology of Parkinson's Disease and Huntington's Disease: A Review.

Alteration in neurotransmitters signaling in basal ganglia has been consistently shown to significantly contribute to the pathophysiological … metabolites and receptor density in basal ganglia region. Although the exact mechanisms underlying neuropathology of movement disorders are not fully understood, but several mechanisms related to neurotransmitters alteration, excitotoxic neuronal death, oxidative stress, mitochondrial dysfunction, neuroinflammation are being put forward. Restoring neurotransmit …

Brain MRI findings related to Alzheimer's disease in older African American adults.

Although a substantial body of research has identified brain MRI measures as important markers of Alzheimer's disease (AD) risk, progression … D risk factors, prevalence of AD, incidence of AD, the clinical course of cognitive decline, and AD neuropathology, each of which could influence the utility of brain MRI markers. Unfortunately, while current evidence suggests that African Americans exhibit poorer brain health late in life based on brain MRI measurements, several other aspects of brain MRI marke …

Histologic Appearance of Iatrogenic Obstructive Hydrocephalus in the Fetal Lamb Model.

INTRODUCTION: Documentation of histologic findings associated with congenital hydrocephalus in the fetal lamb model is a critical step in evaluating the efficacy of ventriculoamniotic shunting in the human fetus. METHODS: Four fetal sheep had hydrocephalus induced at approximately 95 days' gestation. Two co-twins remained as controls. The ewes were euthanized at term. The lamb brains were fixed in formalin, paraffin-embedded, stained, and analyzed for markers of neuropathology. Astrocytosis, microgliosis, and axonal loss were assessed with immunocytochemistry for glial fibrillary acidic prote…

Circuit Mechanisms of Parkinson's Disease.

Parkinson's disease (PD) is a complex, multi-system neurodegenerative disorder. The second most common neurodegenerative disorder after Alzh … al circuit dysfunction. We will first review important disease symptoms and some of the responsible neuropathology. We will then describe the basal ganglia-thalamocortical circuit, the major locus of PD-related circuit dysfunction, and some of the models that have influenced its study. We will review PD-related changes in network activity, subdividing findings i …

Hydroxytyrosol Inhibits LPS-Induced Neuroinflammatory Responses via Suppression of TLR-4-Mediated NF-κB P65 Activation and ERK Signaling Pathway.

Neuroinflammation has been implicated in the mechanism underlying the progression of neurodegeneration and infectious neuropathology. Growing evidence suggest that hydroxytyrosol (3,4-dihydroxyphenil-ethanol, HT), one of the main polyphenols presented in extra virgin olive oil (EVOO), has shown potential anti-inflammatory and neuroprotective effects. However, the potential anti-neuroinflammation activity and underlying mechanism of HT remain poorly understood. The present study aimed to investigate the effects of HT on lipopolysaccharide (LPS)-induced inflammation in both in vitro and in vivo …