A pontine-medullary loop crucial for REM sleep and its deficit in Parkinson's disease.

Identifying the properties of the rapid eye movement (REM) sleep circuitry and its relation to diseases has been challenging due to the neuronal heterogeneity of the brainstem. Here, we show in mice that neurons in the pontine sublaterodorsal tegmentum (SubLDT) that express corticotropin-releasing hormone-binding protein (Crhbp neurons) and project to the medulla promote REM sleep. Within the medullary area receiving projections from Crhbp neurons, neurons expressing nitric oxide synthase 1 (Nos1 neurons) project to the SubLDT and promote REM sleep, suggesting a positively interacting loop between the pons and the medulla operating as a core REM sleep circuit.

Ca -Calmodulin-Calcineurin Signaling Modulates α-Synuclein Transmission.

Background: The intercellular transmission of pathogenic proteins plays a crucial role in the progression of neurodegenerative diseases. Previous research has shown that the neuronal uptake of such proteins is activity-dependent; however, the detailed mechanisms underlying activity-dependent α-synuclein transmission in Parkinson's disease remain unclear.

Objective: To examine whether α-synuclein transmission is affected by Ca -calmodulin-calcineurin signaling in cultured cells and mouse models of Parkinson's disease.

Striatal-Inoculation of α-Synuclein Preformed Fibrils Aggravated the Phenotypes of REM Sleep without Atonia in A53T BAC-SNCA Transgenic Mice.

Accumulation of α-synuclein (α-syn) is the pathological hallmark of α-synucleinopathy. Rapid eye movement (REM) sleep behavior disorder (RBD) is a pivotal manifestation of α-synucleinopathy including Parkinson's disease (PD). RBD is clinically confirmed by REM sleep without atonia (RWA) in polysomnography.

Genetic and clinical landscape of childhood cerebellar hypoplasia and atrophy.

Purpose: Cerebellar hypoplasia and atrophy (CBHA) in children is an extremely heterogeneous group of disorders, but few comprehensive genetic studies have been reported. Comprehensive genetic analysis of CBHA patients may help differentiating atrophy and hypoplasia and potentially improve their prognostic aspects.

Methods: Patients with CBHA in 176 families were genetically examined using exome sequencing.

Lewy Body Disease Primate Model with α-Synuclein Propagation from the Olfactory Bulb.

Background: Lewy body diseases (LBDs), which are pathologically defined as the presence of intraneuronal α-synuclein (α-Syn) inclusions called Lewy bodies, encompass Parkinson's disease, Parkinson's disease with dementia, and dementia with Lewy bodies. Autopsy studies have shown that the olfactory bulb (OB) is one of the regions where Lewy pathology develops and initiates its spread in the brain.

Objective: This study aims to clarify how Lewy pathology spreads from the OB and affects brain functions using nonhuman primates.

Rapid Induction of Dopaminergic Neuron Loss Accompanied by Lewy Body-Like Inclusions in A53T BAC-SNCA Transgenic Mice.

Parkinson's disease (PD), the most common neurodegenerative movement disorder, is characterized by dopaminergic neuron loss in the substantia nigra pars compacta (SNpc) and intraneuronal α-synuclein (α-syn) inclusions. It is highly needed to establish a rodent model that recapitulates the clinicopathological features of PD within a short period to efficiently investigate the pathological mechanisms and test disease-modifying therapies. To this end, we analyzed three mouse lines, i.

Mitochondrial dysfunction in a mouse model of prodromal Parkinson's disease: A metabolomic analysis.

For the development of disease-modifying therapies for Parkinson's disease (PD) the identification of biomarkers in the prodromal stage is urgently required. Because PD is considered a systemic disease even in the early stage, we performed a metabolomic analysis of the plasma from a mouse model of prodromal PD (p-PD). Increased levels of isobutyrylcarnitine in p-PD mice imply an abnormality in β-oxidation in mitochondria, and increased levels of pyrimidine nucleoside can be associated with mitochondrial dysfunction.

Perampanel Inhibits α-Synuclein Transmission in Parkinson's Disease Models.

Background: The intercellular transmission of pathogenic proteins plays a key role in the clinicopathological progression of neurodegenerative diseases. Previous studies have demonstrated that this uptake and release process is regulated by neuronal activity.

Objective: The objective of this study was to examine the effect of perampanel, an antiepileptic drug, on α-synuclein transmission in cultured cells and mouse models of Parkinson's disease.

α-Synuclein Spread from Olfactory Bulb Causes Hyposmia, Anxiety, and Memory Loss in BAC-SNCA Mice.

Background: Patients with Parkinson's disease (PD) show motor symptoms as well as various non-motor symptoms. Postmortem studies of PD have suggested that initial alpha-synuclein (α-Syn) pathology develops independently in the olfactory bulb and lower brainstem, spreading from there stereotypically. However, it remains unclear how these two pathological pathways contribute to the clinicopathological progression of PD.

Developmental Changes in Dendritic Spine Morphology in the Striatum and Their Alteration in an A53T α-Synuclein Transgenic Mouse Model of Parkinson's Disease.

The aging process is accompanied by various neurophysiological changes, and the severity of neurodegenerative disorders such as Parkinson's disease (PD) increases with aging. However, the precise neuroanatomical changes that accompany the aging process in both normal and pathologic conditions remain unknown. This is in part because there is a lack of high-resolution imaging tool that has the capacity to image a desired volume of neurons in a high-throughput and automated manner.

Animal Model for Prodromal Parkinson's Disease.

Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra and subsequent motor symptoms, but various non-motor symptoms (NMS) often precede motor symptoms. Recently, NMS have attracted much attention as a clue for identifying patients in a prodromal stage of PD, which is an excellent point at which to administer disease-modifying therapies (DMTs). These prodromal symptoms include olfactory loss, constipation, and sleep disorders, especially rapid eye movement sleep behavior disorder (RBD), all of which are also important for elucidating the mechanisms of the initiation and progression of the disease.

α-Synuclein BAC transgenic mice exhibit RBD-like behaviour and hyposmia: a prodromal Parkinson's disease model.

Parkinson's disease is one of the most common movement disorders and is characterized by dopaminergic cell loss and the accumulation of pathological α-synuclein, but its precise pathogenetic mechanisms remain elusive. To develop disease-modifying therapies for Parkinson's disease, an animal model that recapitulates the pathology and symptoms of the disease, especially in the prodromal stage, is indispensable. As subjects with α-synuclein gene (SNCA) multiplication as well as point mutations develop familial Parkinson's disease and a genome-wide association study in Parkinson's disease has identified SNCA as a risk gene for Parkinson's disease, the increased expression of α-synuclein is closely associated with the aetiology of Parkinson's disease.

Real-world pharmacological treatment patterns of patients with young-onset Parkinson's disease in Japan: a medical claims database analysis.

Introduction: Young-onset Parkinson's disease is reported to comprise 5-10% of all Parkinson's disease cases; however, as physicians encounter a limited number of these patients, their treatment patterns are still unclear.

Methods: We performed a descriptive study using the large Japanese medical claims database to describe the epidemiology and real-world pharmacological treatment patterns of newly diagnosed patients with young-onset Parkinson's disease. Patients aged 21-50 years in whom Parkinson's disease was newly diagnosed between January 1, 2005 and March 31, 2016 were included.

GBA haploinsufficiency accelerates alpha-synuclein pathology with altered lipid metabolism in a prodromal model of Parkinson's disease.

Parkinson's disease (PD) is characterized by dopaminergic (DA) cell loss and the accumulation of pathological alpha synuclein (asyn), but its precise pathomechanism remains unclear, and no appropriate animal model has yet been established. Recent studies have shown that a heterozygous mutation of glucocerebrosidase (gba) is one of the most important genetic risk factors in PD. To create mouse model for PD, we crossed asyn Bacterial Artificial Chromosome transgenic mice with gba heterozygous knockout mice.

Ser46-Phosphorylated MARCKS Is a Marker of Neurite Degeneration at the Pre-aggregation Stage in PD/DLB Pathology.

Phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) reflects neurite degeneration at the early stage of Alzheimer's disease (AD), before extracellular Aβ aggregates are histologically detectable. Here, we demonstrate that similar changes in MARCKS occur in Parkinson's disease (PD) and dementia with Lewy bodies (DLB) pathologies in both mouse models and human patients. The increase in the level of pSer46-MARCKS began before α-synuclein aggregate formation, at a time when human α-Syn-BAC-Tg/GBA-hetero-KO mice exhibited no symptoms, and was sustained during aging, consistent with the pattern in human postmortem brains.

Selective venous sampling supports localization of adenoma in primary hyperparathyroidism.

Background: Selective venous sampling (SVS) is an invasive localization study for persistent or recurrent hyperparathyroidism.

Purpose: To assess the role of SVS in addition to non-invasive imaging for primary hyperparathyroidism (pHPT).

Material And Methods: This study was approved by the institutional review board and included 14 patients who underwent SVS and subsequent parathyroidectomy between January 2014 and April 2017 following a clinical diagnosis of pHPT.

Selective venous sampling for primary hyperparathyroidism: how to perform an examination and interpret the results with reference to thyroid vein anatomy.

Primary hyperparathyroidism (pHPT) causes hypercalcemia. The treatment for pHPT is surgical dissection of the hyperfunctioning parathyroid gland. Lower rates of hypocalcemia and recurrent laryngeal nerve injury imply that minimally invasive parathyroidectomy (MIP) is safer than bilateral neck resection.

Animal models for Parkinson's disease.

Parkinson's disease (PD) is one of the most common degenerative disorders of the CNS, characterized by motor syndrome, for example, tremor, rigidity, bradykinesia, and postural instability. Parkinson's disease was first described in 1817, but the pathogenesis still remains unclear. An animal model is very important, in order to explore the pathogenesis, to search for translatable biomarkers, and verify the efficacy of experimental therapeutic interven- tions.

Ultraselective transcatheter arterial chemoembolization for small hepatocellular carcinoma guided by automated tumor-feeders detection software: technical success and short-term tumor response.

Purpose: To analyze the technical success and tumor response of ultraselective transcatheter arterial chemoembolization (TACE) for small hepatocellular carcinoma (HCC) using automated tumor-feeders detection (AFD) software.

Methods: Prototype AFD software was prospectively applied to cone-beam computed tomography images acquired during TACE for 155 consecutive HCCs ≤50 mm in 81 patients. The detectability of tumor-feeding subsubsegmental arteries was analyzed.

Percutaneous transluminal angioplasty of a non-mainstream venous route to restore an occluded hemodialysis fistula.

Purpose: To report the usefulness of percutaneous transluminal angioplasty (PTA) of a non-mainstream venous route in an occluded native hemodialysis fistula when a mainstream outflow vein could not be traversed.

Materials And Methods: This cohort included seven patients with an occulted hemodialysis fistula with difficulty in traversing via a mainstream route. A non-mainstream vein near the occluded portion was traversed until it connected with a proximal large-sized vein and the route was dilated using a 4- or 5-mm balloon catheter.

Comparison of local control in transcatheter arterial chemoembolization of hepatocellular carcinoma ≤6 cm with or without intraprocedural monitoring of the embolized area using cone-beam computed tomography.

Purpose: This study was designed to compare technical success and local recurrence rates of transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) with/without monitoring of embolized areas using cone-beam computed tomography (CBCT).

Methods: A total of 207 HCCs ≤6 cm were treated with superselective TACE using digital subtraction angiography (DSA) alone (DSA group, 98 tumors of 70 patients) or plus CBCT monitoring (CBCT group, 109 tumors of 79 patients). Technical success of TACE was classified into three grades according to 1-week CT; the tumor was embolized with a safety margin (5-mm wide for tumors <25 mm, and 10-mm wide for tumors 25≥ and ≤60 mm; grade A), without a margin in parts (grade B), or the entire tumor was not embolized (grade C).

Identification of small hepatocellular carcinoma and tumor-feeding branches with cone-beam CT guidance technology during transcatheter arterial chemoembolization.

Purpose: To evaluate the performance of transcatheter arterial chemoembolization guidance software that uses cone-beam computed tomography (CT) technology in identifying small hepatocellular carcinoma (HCC) tumors and feeding branches.

Materials And Methods: Cone-beam CT and manual feeder vessel detection (MFD) software were used in chemoembolization of 68 HCCs 30 mm or smaller (mean ± standard deviation, 15.3 mm ± 5.

Blood supply of the main bile duct from the caudate artery and medial subsegmental artery of the hepatic artery: Evaluation using images obtained during transcatheter arterial chemoembolization for hepatocellular carcinoma.

Aim: Main bile duct necrosis develops after transcatheter arterial chemoembolization (TACE) through the caudate artery (A1) and medial subsegmental artery (A4) of the hepatic artery in the treatment of hepatocellular carcinoma. The aim of this study was to evaluate the bile duct branch (BD branch) from A1 and A4.

Methods: We evaluated the origin and vascular territory of the BD branch in 11 patients who underwent selective A1 and/or A4 arteriography using arteriograms, cone-beam computed tomography (CBCT) and CT obtained 1 week after TACE.

Clinical features of hepatocellular carcinoma supplied by the left internal mammary artery.

Purpose: To evaluate the clinical features of hepatocellular carcinoma (HCC) supplied by the left internal mammary artery (LIMA).

Materials And Methods: This cohort included 12 HCCs of 12 patients supplied by the LIMA. The clinical features of these tumors were analyzed.