Search results for "Nervous system"

New insights in the neurological phenotype of aceruloplasminemia in Caucasian patients

2017

Abstract Introduction The diagnosis aceruloplasminemia is usually made in patients with advanced neurological manifestations of the disease. In these patients prognosis is poor, disabilities are severe and patients often die young. The aim of our study was to facilitate recognition of aceruloplasminemia at a disease stage at which treatment can positively influence outcome. Currently, the neurological phenotype of aceruloplasminemia has been mainly described in Japanese patients. This ‘classical’ phenotype consists of cerebellar ataxia, hyperkinetic movement disorders and cognitive decline. In this study we describe the spectrum of neurological disease in Caucasian patients. Methods Data on…

Clinical implications of serum neurofilament in newly diagnosed MS patients: a longitudinal multicentre cohort study

2020

Abstract Background We aim to evaluate serum neurofilament light chain (sNfL), indicating neuroaxonal damage, as a biomarker at diagnosis in a large cohort of early multiple sclerosis (MS) patients. Methods In a multicentre prospective longitudinal observational cohort, patients with newly diagnosed relapsing-remitting MS (RRMS) or clinically isolated syndrome (CIS) were recruited between August 2010 and November 2015 in 22 centers. Clinical parameters, MRI, and sNfL levels (measured by single molecule array) were assessed at baseline and up to four-year follow-up. Findings Of 814 patients, 54.7% (445) were diagnosed with RRMS and 45.3% (369) with CIS when applying 2010 McDonald criteria (R…

Heart rate acceleration at relative workloads during treadmill and overground running for tracking exercise performance during functional overreaching

2020

AbstractMaximal rate of heart rate (HR) increase (rHRI) as a measure of HR acceleration during the transition from rest to exercise, or during an increase in workload, tracks exercise performance. rHRI assessed at relative rather than absolute workloads may track performance better, and a field test would increase applicability. This study therefore aimed to evaluate the sensitivity of rHRI assessed at individualised relative workloads during treadmill and overground running for tracking exercise performance. Treadmill running performance (5 km time trial; 5TTT) and rHRI were assessed in 11 male runners following 1 week of light training (LT), 2 weeks of heavy training (HT) and a 10-day tap…

Viral encephalitis in Parry-Romberg syndrome

2019

A 28-year-old woman was admitted to our clinic for acute onset of headache, aphasia and confusion, followed by a first episode of generalised tonic–clonic seizures. She had a history of left-sided migraine, accompanied by visual aura and right arm dysesthesia since the age of 20 years and

Cholesterol Hydroxylating Cytochrome P450 46A1: From Mechanisms of Action to Clinical Applications

2021

Cholesterol, an essential component of the brain, and its local metabolism are involved in many neurodegenerative diseases. The blood-brain barrier is impermeable to cholesterol; hence, cholesterol homeostasis in the central nervous system represents a balance betweenin situbiosynthesis and elimination. Cytochrome P450 46A1 (CYP46A1), a central nervous system-specific enzyme, converts cholesterol to 24-hydroxycholesterol, which can freely cross the blood-brain barrier and be degraded in the liver. By the dual action of initiating cholesterol efflux and activating the cholesterol synthesis pathway, CYP46A1 is the key enzyme that ensures brain cholesterol turnover. In humans and mouse models,…

Neuronal inhibition of the autophagy nucleation complex extends life span in post-reproductive C. elegans

2017

Autophagy is a ubiquitous catabolic process that causes cellular bulk degradation of cytoplasmic components and is generally associated with positive effects on health and longevity. Inactivation of autophagy has been linked with detrimental effects on cells and organisms. The antagonistic pleiotropy theory postulates that some fitness-promoting genes during youth are harmful during aging. On this basis, we examined genes mediating post-reproductive longevity using an RNAi screen. From this screen, we identified 30 novel regulators of post-reproductive longevity, including pha-4. Through downstream analysis of pha-4, we identified that the inactivation of genes governing the early stages of…

Electrical activity controls area-specific expression of neuronal apoptosis in the mouse developing cerebral cortex

2017

Programmed cell death widely but heterogeneously affects the developing brain, causing the loss of up to 50% of neurons in rodents. However, whether this heterogeneity originates from neuronal identity and/or network-dependent processes is unknown. Here, we report that the primary motor cortex (M1) and primary somatosensory cortex (S1), two adjacent but functionally distinct areas, display striking differences in density of apoptotic neurons during the early postnatal period. These differences in rate of apoptosis negatively correlate with region-dependent levels of activity. Disrupting this activity either pharmacologically or by electrical stimulation alters the spatial pattern of apoptos…

Adult rat myelin enhances axonal outgrowth from neural stem cells.

2018

Axon regeneration after spinal cord injury (SCI) is attenuated by growth inhibitory molecules associated with myelin. We report that rat myelin stimulated the growth of axons emerging from rat neural progenitor cells (NPCs) transplanted into sites of SCI in adult rat recipients. When plated on a myelin substrate, neurite outgrowth from rat NPCs and from human induced pluripotent stem cell (iPSC)-derived neural stem cells (NSCs) was enhanced threefold. In vivo, rat NPCs and human iPSC-derived NSCs extended greater numbers of axons through adult central nervous system white matter than through gray matter and preferentially associated with rat host myelin. Mechanistic investigations excluded …

2019

These days, the important role of retinoids in adult brain functionality and homeostasis is well accepted and has been proven by genomic as well as non-genomic mechanisms. In the healthy brain, numerous biological processes, e.g., cell proliferation, neurogenesis, dendritic spine formation as well as modulation of the immune system, have been attributed to retinoid signaling. This, together with the finding that retinoid metabolism is impaired in Alzheimer's disease (AD), led to preclinical and early clinical testing of natural and synthetic retinoids as innovative pharmaceuticals with multifactorial properties. Acitretin, an aromatic retinoid, was found to exert an anti-amyloidogenic effec…

Differential Associations of IL-4 With Hippocampal Subfields in Mild Cognitive Impairment and Alzheimer’s Disease

2019

Background/Aims: A bi-directional communication between the immune system and the central nervous system has been recently suggested. Among many cytokines, the role of IL-4 - with anti-inflammatory properties- in counteracting age-related inflammatory changes in the brain is strongly supported among studies. With this study, we aimed at investigating the association between volumetric measures of hippocampal subregions -in healthy older controls (HC), subjects affected by mild cognitive impairment (MCI) and Alzheimer’s Disease (AD)- with circulating levels of IL-4. Methods: From AddNeuroMed Project 113 HC, 101 stable MCI (sMCI), 22 converter MCI (cMCI) and 119 AD were included. Hippocampal …