13,345 results match your criteria midbrain pathology


Prenatal diagnosis of rhombencephalosynapsis: neuroimaging features and severity of vermian anomaly.

Ultrasound Obstet Gynecol 2021 May 4. Epub 2021 May 4.

Fetal Neurology Multidisciplinary Group, Division of Ultrasound in Obstetrics and Gynecology, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

Objectives: To describe the prenatal neuroimaging spectrum of rhombencephalosynapsis (RES) and the criteria for the classification according to the severity of the vermian anomaly. Methods In this multicenter retrospective study of fetuses with a diagnosis of RES, the medical records, ultrasound and brain MR images were comprehensively evaluated for the severity of the vermian anomaly and the presence of associated brain findings. RES was classified based on the criteria suggested by Ishak et al. Read More

View Article and Full-Text PDF

Active lifestyle enhances protein expression profile in subjects with Lewy body pathology.

Dement Neuropsychol 2021 Jan-Mar;15(1):41-50

Laboratory of Cellular Neurobiology, Department of Physiology and Biophysics, Instituto de Ciencias Biomedicas, Universidade de São Paulo - São Paulo, SP, Brazil.

Clinical trials of the effects of physical activity have reported improvements in symptoms and quality of life in patients with Parkinson's disease (PD). Additionally, morphological brain changes after exercising were reported in PD animal models. However, these lifestyle-related changes were not evaluated in postmortem brain tissue. Read More

View Article and Full-Text PDF

Nurr1 repression mediates cardinal features of Parkinson's Disease in α-synuclein transgenic mice.

Hum Mol Genet 2021 Apr 26. Epub 2021 Apr 26.

Center for Clinical Research, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens 11527, Greece.

Duplication/triplication mutations of the SNCA locus, encoding alpha-synuclein (ASYN), and loss of function mutations in Nurr1, a nuclear receptor guiding midbrain dopaminergic neuron development, are associated with familial Parkinson's disease (PD). As we age, the expression levels of these two genes in midbrain dopaminergic neurons follow opposite directions and ASYN expression increases while the expression of Nurr1 decreases. We investigated the effect of ASYN and Nurr1 age-related expression alterations in the pathogenesis of PD by coupling Nurr1 hemizygous with ASYN(s) (heterozygote) or ASYN(d) (homozygote) transgenic mice. Read More

View Article and Full-Text PDF

Comparison of Locus Coeruleus Pathology with Nigral and Forebrain Pathology in Parkinson's Disease.

Mov Disord 2021 Apr 26. Epub 2021 Apr 26.

ForeFront Research Team, Brain and Mind Centre and Faculty of Medicine and Health School of Medical Sciences, The University of Sydney, Sydney, New South Wales, Australia.

Background: Pathology in the noradrenergic A6 locus coeruleus has not been compared with more rostral dopaminergic A9 substantia nigra and A10 ventral tegmental area, and cholinergic Ch4 basal nucleus and Ch1/2 septal regions in the same cases of Parkinson's disease (PD).

Objective: To determine whether there is a gradient of caudal to rostral cell loss in PD.

Methods: Postmortem brains were collected from longitudinally followed donors with PD (n = 14) and aged-matched healthy donors (n = 13), six with restricted brainstem Lewy pathology (RLP), fixed in formalin and serial tissue slabs processed for cell and pathological quantitation. Read More

View Article and Full-Text PDF

Artery of Percheron infarction: A case report and literature review.

Radiol Case Rep 2021 Jun 28;16(6):1271-1275. Epub 2021 Mar 28.

University Clinical Center, Clinic of Radiology, University for Business and Technology - Radiology.

The artery of Percheron (AOP) represents a rare anatomic variant of the posterior circulation. It is a solitary trunk that provides bilateral arterial supply to the rostral midbrain and paramedian thalamus. AOP infarction presentation varies, most often presents with altered mental status, memory impairment, and supranuclear vertical gaze palsy. Read More

View Article and Full-Text PDF

Single-Cell Transcriptomics and Morphological Analyses Reveal Microglia Heterogeneity Across the Nigrostriatal Pathway.

Front Immunol 2021 29;12:639613. Epub 2021 Mar 29.

Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg.

Microglia are the resident immune effector cells of the central nervous system (CNS) rapidly reacting to various pathological stimuli to maintain CNS homeostasis. However, microglial reactions in the CNS may also worsen neurological disorders. Hence, the phenotypic analysis of microglia in healthy tissue may identify specific poised subsets ultimately supporting or harming the neuronal network. Read More

View Article and Full-Text PDF

Crotalaria spectabilis poisoning in horses fed contaminating oats.

Toxicon 2021 Apr 18;197:6-11. Epub 2021 Apr 18.

Large Animal Veterinary Teaching Hospital, College of Agronomy and Veterinary Medicine, Universidade de Brasília, Galpão 4, Granja do Torto, Brasília, DF 70636-200, Brazil. Electronic address:

The present report describes the clinical and pathological changes induced by the consumption of oats contaminated with Crotalaria spectabilis seeds by horses. Eighty horses were exposed to oats containing 10 g/kg of C. spectabilis seeds with 0. Read More

View Article and Full-Text PDF

Intracerebral Administration of a Ligand-ASO Conjugate Selectively Reduces α-Synuclein Accumulation in Monoamine Neurons of Double Mutant Human A30P*A53T*α-Synuclein Transgenic Mice.

Int J Mol Sci 2021 Mar 13;22(6). Epub 2021 Mar 13.

Institut d'Investigacions Biomèdiques de Barcelona (IIBB), Spanish National Research Council (CSIC), 08036 Barcelona, Spain.

α-Synuclein (α-Syn) protein is involved in the pathogenesis of Parkinson's disease (PD). Point mutations and multiplications of the α-Syn, which encodes the gene, are correlated with early-onset PD, therefore the reduction in a-Syn synthesis could be a potential therapy for PD if delivered to the key affected neurons. Several experimental strategies for PD have been developed in recent years using oligonucleotide therapeutics. Read More

View Article and Full-Text PDF

Parkinson's disease and mitophagy: an emerging role for LRRK2.

Biochem Soc Trans 2021 Apr;49(2):551-562

MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee DD1 5EH, U.K.

Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects around 2% of individuals over 60 years old. It is characterised by the loss of dopaminergic neurons in the substantia nigra pars compacta of the midbrain, which is thought to account for the major clinical symptoms such as tremor, slowness of movement and muscle stiffness. Its aetiology is poorly understood as the physiological and molecular mechanisms leading to this neuronal loss are currently unclear. Read More

View Article and Full-Text PDF

Machine learning-based decision tree classifier for the diagnosis of progressive supranuclear palsy and corticobasal degeneration.

Neuropathol Appl Neurobiol 2021 Mar 24. Epub 2021 Mar 24.

Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.

Aims: This study aimed to clarify the different topographical distribution of tau pathology between progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) and establish a machine learning-based decision tree classifier.

Methods: Paraffin-embedded sections of the temporal cortex, motor cortex, caudate nucleus, globus pallidus, subthalamic nucleus, substantia nigra, red nucleus, and midbrain tectum from 1020 PSP and 199 CBD cases were assessed by phospho-tau immunohistochemistry. The severity of tau lesions (i. Read More

View Article and Full-Text PDF

Methods to Induce Small-Scale Differentiation of iPS Cells into Dopaminergic Neurons and to Detect Disease Phenotypes.

Methods Mol Biol 2021 Mar 24. Epub 2021 Mar 24.

Center for Genomic and Regenerative Medicine, Juntendo University School of Medicine, Tokyo, Japan.

Disease-specific induced pluripotent stem (iPS) cells are useful tools to analyze the pathology of neurodegenerative diseases. In this chapter, we describe a procedure to efficiently induce small-scale differentiation of patient iPS cells into midbrain dopaminergic neurons to detect cell death and mitochondrial clearance by using immunostaining. A combination of our method described here and an image analysis system, such as the IN Cell Analyzer, will enable the quantitative assessment of cell vulnerability and mitochondrial quality control abnormalities in cells derived from patients with Parkinson's disease; this set-up might be used to perform drug screening. Read More

View Article and Full-Text PDF

Graded recruitment of pupil-linked neuromodulation by parametric stimulation of the vagus nerve.

Nat Commun 2021 03 9;12(1):1539. Epub 2021 Mar 9.

Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA.

Vagus nerve stimulation (VNS) is thought to affect neural activity by recruiting brain-wide release of neuromodulators. VNS is used in treatment-resistant epilepsy, and is increasingly being explored for other disorders, such as depression, and as a cognitive enhancer. However, the promise of VNS is only partially fulfilled due to a lack of mechanistic understanding of the transfer function between stimulation parameters and neuromodulatory response, together with a lack of biosensors for assaying stimulation efficacy in real time. Read More

View Article and Full-Text PDF

Neural crest cell-derived pericytes act as pro-angiogenic cells in human neocortex development and gliomas.

Fluids Barriers CNS 2021 Mar 20;18(1):14. Epub 2021 Mar 20.

Department of Basic Medical Sciences, Neuroscience and Sensory Organs, Human Anatomy and Histology Unit, University of Bari School of Medicine, Bari, Italy.

Central nervous system diseases involving the parenchymal microvessels are frequently associated with a 'microvasculopathy', which includes different levels of neurovascular unit (NVU) dysfunction, including blood-brain barrier alterations. To contribute to the understanding of NVU responses to pathological noxae, we have focused on one of its cellular components, the microvascular pericytes, highlighting unique features of brain pericytes with the aid of the analyses carried out during vascularization of human developing neocortex and in human gliomas. Thanks to their position, centred within the endothelial/glial partition of the vessel basal lamina and therefore inserted between endothelial cells and the perivascular and vessel-associated components (astrocytes, oligodendrocyte precursor cells (OPCs)/NG2-glia, microglia, macrophages, nerve terminals), pericytes fulfil a central role within the microvessel NVU. Read More

View Article and Full-Text PDF

Minocycline alleviates the symptoms of morphine withdrawal via the CaMKII-Ras-ERK signaling pathway.

Neurosci Lett 2021 05 13;752:135825. Epub 2021 Mar 13.

Department of Pathology and Pathophysiology, Chengdu Medical College, Chengdu, China; Department of Pathogenic Biology, Chengdu Medical College, Chengdu, China. Electronic address:

Objective: To investigate the effect of minocycline on morphine withdrawal symptoms.

Methods: We established a rat model of morphine dependence, then injected the animals with naloxone to induce withdrawal symptoms. Minocycline was injected into the midbrain periaqueductal gray and its effect on withdrawal symptoms and Ca-dependent protein kinase (CaMKII), Ras, and phospho-extracellular signal-regulated kinase (p-ERK) expression was observed. Read More

View Article and Full-Text PDF

An extended release GLP-1 analogue increases α-synuclein accumulation in a mouse model of prodromal Parkinson's disease.

Exp Neurol 2021 Mar 13;341:113693. Epub 2021 Mar 13.

Parkinson's Disease Center, Department of Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI, USA. Electronic address:

The repurposing of drugs developed to treat type 2 diabetes for the treatment of Parkinson's disease (PD) was encouraged by the beneficial effect exerted by the glucagon-like peptide 1 (GLP-1) analogue exenatide in a phase 2 clinical trial. The effects of GLP-1 analogues have been investigated extensively using rodent toxin models of PD. However, many of the toxin-based models used lack robust α-synuclein (α-syn) pathology, akin to the Lewy bodies and neurites seen in PD. Read More

View Article and Full-Text PDF

The Third Eye Sees Double: Cohort Study of Clinical Presentation, Histology, Surgical Approaches, and Ophthalmic Outcomes in Pineal Region Germ Cell Tumors.

World Neurosurg 2021 Mar 17. Epub 2021 Mar 17.

Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota, USA. Electronic address:

Background: Intracranial germ cell tumors (GCTs) predominantly occur in the adolescent and young adult population and are most frequently located at the pineal gland. Tumor masses in the pineal region may cause ophthalmic symptoms due to compression to the midbrain, frequently presenting with Parinaud syndrome and hydrocephalus due to aqueductal compression.

Methods: We conducted a single-institution cohort study of primary, pineal region GCTs to characterize the clinical presentation, as well as associated ophthalmic and hydrocephalus outcomes. Read More

View Article and Full-Text PDF

Infratentorial onset of progressive multifocal leukoencephalopathy in a patient with systematic lupus erythematosus complicated with lymphoma: a case report.

Mod Rheumatol Case Rep 2021 Apr 6:1-6. Epub 2021 Apr 6.

Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan.

Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection of the central nervous system caused by reactivation of JC virus (JCV). Typical PML shows confluent, bilateral but asymmetric, subcortical lesions in the supratentorial white matter on magnetic resonance imaging (MRI). We report here a 50-year-old woman with systemic lupus erythematosus complicated with lymphoma who developed PML with atypical brain MRI findings limited to the infratentorial area at presentation. Read More

View Article and Full-Text PDF

CD4 T cells mediate brain inflammation and neurodegeneration in a mouse model of Parkinson disease.

Brain 2021 Mar 11. Epub 2021 Mar 11.

Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, The University of Alabama at Birmingham, Birmingham, AL, 35294, USA.

α-synuclein (α-syn), a key pathological component of Parkinson disease (PD), has been implicated in the activation of the innate and adaptive immune system. This immune activation includes microgliosis, increased inflammatory cytokines, and the infiltration of T cells into the central nervous system (CNS). More recently, peripherally circulating CD4 and CD8 T cells derived from individuals with PD have been shown to produce Th1/Th2 cytokines in response to α-syn, suggesting there may be a chronic memory T cell response present in PD. Read More

View Article and Full-Text PDF

Age-associated insolubility of parkin in human midbrain is linked to redox balance and sequestration of reactive dopamine metabolites.

Acta Neuropathol 2021 05 10;141(5):725-754. Epub 2021 Mar 10.

Department of Neurobiology, Duke University, Durham, NC, USA.

The mechanisms by which parkin protects the adult human brain from Parkinson disease remain incompletely understood. We hypothesized that parkin cysteines participate in redox reactions and that these are reflected in its posttranslational modifications. We found that in post mortem human brain, including in the Substantia nigra, parkin is largely insoluble after age 40 years; this transition is linked to its oxidation, such as at residues Cys95 and Cys253. Read More

View Article and Full-Text PDF

Discovering the Lost Reward: Critical Locations for Endocannabinoid Modulation of the Cortico-Striatal Loop That Are Implicated in Major Depression.

Int J Mol Sci 2021 Feb 13;22(4). Epub 2021 Feb 13.

Department of Biological Sciences, University of Texas at El Paso, El Paso, TX 79968, USA.

Depression, the most prevalent psychiatric disorder in the Western world, is characterized by increased negative affect (i.e., depressed mood, cost value increase) and reduced positive affect (i. Read More

View Article and Full-Text PDF
February 2021

Paraoxonase-1 and -3 Protein Expression in the Brain of the Tg2576 Mouse Model of Alzheimer's Disease.

Antioxidants (Basel) 2021 Feb 24;10(3). Epub 2021 Feb 24.

Department of Psychology and Research Center for Behavioral Assessment (CRAMC), Universitat Rovira i Virgili, 43007 Tarragona, Spain.

Background: Brain oxidative lipid damage and inflammation are common in neurodegenerative diseases such as Alzheimer's disease (AD). Paraoxonase-1 and -3 (PON1 and PON3) protein expression was demonstrated in tissue with no or gene expression. In the present study, we examine differences in PON1 and PON3 protein expression in the brain of a mouse model of AD. Read More

View Article and Full-Text PDF
February 2021

LRRK2; a dynamic regulator of cellular trafficking.

Brain Res 2021 Mar 2;1761:147394. Epub 2021 Mar 2.

Laboratory of Neurogenetics and Neuroscience, Department of Neurology, University of Florida, Gainesville, FL, USA.

Parkinson's disease (PD) represents the second most common neurodegenerative disorder, characterized clinically by bradykinesia, resting tremor, rigidity and postural instability, and a variety of non-motor features. The etiology of PD is unknown, however genetic, environmental and inflammatory factors may influence disease onset and progression. Genetic variability in leucine-rich repeat kinase 2 confers significant genotypic and population-attributable risk for LRRK2-parkinsonism that is clinically indistinguishable from idiopathic PD. Read More

View Article and Full-Text PDF

Autologous transplant therapy alleviates motor and depressive behaviors in parkinsonian monkeys.

Nat Med 2021 04 1;27(4):632-639. Epub 2021 Mar 1.

Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.

Degeneration of dopamine (DA) neurons in the midbrain underlies the pathogenesis of Parkinson's disease (PD). Supplement of DA via L-DOPA alleviates motor symptoms but does not prevent the progressive loss of DA neurons. A large body of experimental studies, including those in nonhuman primates, demonstrates that transplantation of fetal mesencephalic tissues improves motor symptoms in animals, which culminated in open-label and double-blinded clinical trials of fetal tissue transplantation for PD. Read More

View Article and Full-Text PDF

SGK1 inhibition in glia ameliorates pathologies and symptoms in Parkinson disease animal models.

EMBO Mol Med 2021 Apr 1;13(4):e13076. Epub 2021 Mar 1.

Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul, Korea.

Astrocytes and microglia are brain-resident glia that can establish harmful inflammatory environments in disease contexts and thereby contribute to the progression of neuronal loss in neurodegenerative disorders. Correcting the diseased properties of glia is therefore an appealing strategy for treating brain diseases. Previous studies have shown that serum/ glucocorticoid related kinase 1 (SGK1) is upregulated in the brains of patients with various neurodegenerative disorders, suggesting its involvement in the pathogenesis of those diseases. Read More

View Article and Full-Text PDF

Brainstem substructures and cognition in prodromal Alzheimer's disease.

Brain Imaging Behav 2021 Mar 1. Epub 2021 Mar 1.

Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, USA.

Neuropathological research suggests the tau pathology of Alzheimer's disease may originate in brainstem nuclei, yet it remains unknown whether tau-mediated degeneration of brainstem nuclei influences cognitive impairment in prodromal Alzheimer's disease. The present study examined cognitive domains impacted in prodromal Alzheimer's disease and brainstem substructure volume in cognitively normal older adults (n = 814) and those with mild cognitive impairment (n = 542). Subsamples of cognitively normal (n = 112) and mild cognitive impairment (n = 202) also had cerebrospinal fluid Alzheimer's disease biomarker characterization. Read More

View Article and Full-Text PDF

Mapping the living mouse brain neural architecture: strain-specific patterns of brain structural and functional connectivity.

Brain Struct Funct 2021 Apr 26;226(3):647-669. Epub 2021 Feb 26.

Department of Radiology, Medical Physics, Medical Center, Faculty of Medicine, University of Freiburg, Breisacher Straße 60a, 79106, Freiburg, Germany.

Mapping brain structural and functional connectivity (FC) became an essential approach in neuroscience as network properties can underlie behavioral phenotypes. In mouse models, revealing strain-related patterns of brain wiring is crucial, since these animals are used to answer questions related to neurological or neuropsychiatric disorders. C57BL/6 and BALB/cJ strains are two of the primary "genetic backgrounds" for modeling brain disease and testing therapeutic approaches. Read More

View Article and Full-Text PDF

Latent trait modeling of tau neuropathology in progressive supranuclear palsy.

Acta Neuropathol 2021 05 26;141(5):667-680. Epub 2021 Feb 26.

Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.

Progressive supranuclear palsy (PSP) is the second most common neurodegenerative Parkinsonian disorder after Parkinson's disease, and is characterized as a primary tauopathy. Leveraging the considerable clinical and neuropathologic heterogeneity associated with PSP, we measured tau neuropathology as quantitative traits to perform a genome-wide association study (GWAS) within PSP to identify genes and biological pathways that underlie the PSP disease process. In 882 PSP cases, semi-quantitative scores for phosphorylated tau-immunoreactive coiled bodies (CBs), neurofibrillary tangles (NFTs), tufted astrocytes (TAs), and tau threads were documented from 18 brain regions, and converted to latent trait (LT) variables using the R ltm package. Read More

View Article and Full-Text PDF

Neurodevelopmental defects and neurodegenerative phenotypes in human brain organoids carrying Parkinson's disease-linked mutations.

Sci Adv 2021 Feb 17;7(8). Epub 2021 Feb 17.

Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul, Republic of Korea.

Loss-of-function mutations of , encoding HSP40 auxilin, have recently been identified in patients with early-onset Parkinson's disease (PD). To study the roles of DNAJC6 in PD pathogenesis, we used human embryonic stem cells with CRISPR-Cas9-mediated gene editing. Here, we show that mutations cause key PD pathologic features, i. Read More

View Article and Full-Text PDF
February 2021

Neuroanatomical MRI study: reference values for the measurements of brainstem, cerebellar vermis, and peduncles.

Br J Radiol 2021 Apr 17;94(1120):20201353. Epub 2021 Feb 17.

Department of Radio-diagnosis, Zagazig University, Zagazig, AlSharkia, Egypt.

Objectives: To set age-specific normal reference values for brainstem, cerebellar vermis, and peduncles measurements and characterize values' variations according to gender, age, and age by gender interaction.

Methods: 565 normal brain magnetic resonance examinations with normal anatomy and signal intensity of the supra- and infratentorial structures were categorized into six age groups (infant, child, adolescent, young adult, middle-age adult, and old aged adults). Patients with congenital malformations, gross pathology of the supra- or infratentorial brain, brain volume loss, developmental delay, metabolic disorders, and neuropsychological disorders ( = 2. Read More

View Article and Full-Text PDF

[Comparative Analysis of MPTP Neurotoxicity in Mice with a Constitutive Knockout of the α-Synuclein Gene].

Mol Biol (Mosk) 2021 Jan-Feb;55(1):152-163

Institute of Physiologically Active Compounds, Russian Academy of Sciences, Chernogolovka, Moscow oblast, 142432 Russia.

Aggregated forms of α-synuclein are core components of pathohistological inclusions known as Lewy bodies in substantia nigra (SN) neurons of patients with Parkinson's disease (PD). The role of α-synuclein in selective loss of SN dopaminergic neurons (DNs) in PD is studied in mice knocked out in the α-synuclein gene. The new mouse strain delta flox KO with a constitutive knockout of the α-synuclein gene models the end point of in vivo deletion of the α-synuclein gene in mice with a conditional knockout and has no foreign sequence in the modified genomic locus, thus differing from all other α-synuclein knockout mouse strains. Read More

View Article and Full-Text PDF
February 2021