Expression and role of nicotinic acetylcholine receptors during midbrain dopaminergic neuron differentiation from human induced pluripotent stem cells.

Aim: Nicotinic acetylcholine receptors (nAChRs) expressed in midbrain dopaminergic (mDA) neurons modulate mDA neuronal activity. However, their expression patterns and functional roles during mDA neuronal development remain unknown. Here, we profiled the expression and function of nAChR subtypes during mDA neuron differentiation from human induced pluripotent stem cells (hiPSCs).

[Morvan syndrome associated with unresectable thymoma responsive to chemotherapy: a case report].

A 51-year-old Japanese man presenting with a several-month history of parasomnia, orthostatic hypotension and generalized myokymia was admitted to our hospital. He had a past medical history of unresectable recurrent thymoma, but chemotherapy for thymoma was discontinued according to the patient's decision four years before this hospitalization, and the thymoma had enlarged. He exhibited symptoms of the peripheral nervous system (myokymia), central nervous system (parasomnia, short-term memory impairment), and autonomic nervous system (orthostatic hypotension), and his serum was positive for voltage-gated potassium channel (VGKC)-complex antibodies.

[A case of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) complicated by chronic intestinal pseudo-obstruction].

A 42-year-old woman presented at our hospital with acute paraphasia and word finding difficulty. She was not paralyzed or ataxic. Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) was diagnosed based on brain MRI finding of edematous lesions in bilateral temporal lobe cortexes that did not match the vascular territory, elevated lactate and pyruvate levels in blood and cerebrospinal fluid, and the presence of a mtDNA 3243A>G mutation.

Nicotinic Acetylcholine Receptors and Microglia as Therapeutic and Imaging Targets in Alzheimer's Disease.

Amyloid-β (Aβ) accumulation and tauopathy are considered the pathological hallmarks of Alzheimer's disease (AD), but attenuation in choline signaling, including decreased nicotinic acetylcholine receptors (nAChRs), is evident in the early phase of AD. Currently, there are no drugs that can suppress the progression of AD due to a limited understanding of AD pathophysiology. For this, diagnostic methods that can assess disease progression non-invasively before the onset of AD symptoms are essential, and it would be valuable to incorporate the concept of neurotheranostics, which simultaneously enables diagnosis and treatment.

Ubiquitin-dependent rapid degradation conceals a cell-protective function of cytoplasmic SIRT3 against oxidative stress.

SIRT3 is an NAD+-dependent protein deacetylase localized in mitochondria. Several studies reported localization of SIRT3 in the cytoplasm or nucleus, but data of these studies were not consistent. We detected expression of mitochondrial (SIRT3mt) and cytoplasmic (SIRT3ct) Sirt3 mRNAs in the mouse brain, and we also found SIRT3 immunostaining of mitochondria and cytoplasm in the brain and cultured neural cells.

[A case of neuronal intranuclear inclusion disease with serial MRI changes observed from before onset of forgetfulness].

A 70-year-old woman presented with a 6-year history of cognitive dysfunction, neurogenic bladder, constipation and recurrent vomiting, and gradual worsening of symptoms. At the first admission to our department, she was also found to have hepatic encephalopathy due to intrahepatic portosystemic shunt. Head MRI revealed abnormal signal intensity at the corticomedullary junction, the splenium of the corpus callosum, and bilateral middle cerebellar peduncles on DWI.

Abrupt Onset of Cardiac Tamponade in Sarcoidosis.

Sarcoidosis is a systemic inflammatory disease characterized by the formation of noncaseating epithelioid granulomas. Multiple organs, including the lung, eyes, and skin, are involved in this disorder, and cardiac involvement is a major cause of morbidity and mortality in patients with this disorder. We present the case history of a 22-year-old man with neurosarcoidosis complicated by abrupt onset of cardiac tamponade.

Roles of microglia in Alzheimer's disease and impact of new findings on microglial heterogeneity as a target for therapeutic intervention.

Microglia are specialized macrophages that reside within the central nervous system and play key roles in brain immunity, development and homeostasis. Recent studies also revealed functions of microglia in neuroprotection and neuroinflammation, leading to the discovery that microglia are involved in several brain pathologies including Alzheimer's disease (AD). However, the beneficial and detrimental actions of this intriguing cell population can be challenging to dissect: the advent of single-cell and single-nucleus transcriptomic technologies has revolutionized our understanding of the heterogeneity of multiple cell types and is now being applied to the study of microglia in health and disease.

Generation of striatal neurons from human induced pluripotent stem cells by controlling extrinsic signals with small molecules.

Human induced pluripotent stem cells (hiPSCs) are powerful tools for modeling human brain development and treating neurodegenerative diseases. Here we established a robust protocol with high scalability for generating striatal medium spiny neurons (MSNs) from hiPSCs using small molecules under two- and three-dimensional culture conditions. Using this protocol, GSH2 lateral ganglionic eminence (LGE) progenitors were generated in two-dimensional culture by Sonic hedgehog signaling activation using purmorphamine, WNT signaling inhibition using XAV939, and dual-SMAD inhibition using LDN193189 and A83-01.

Early detection of redox imbalance in the APPswe/PS1dE9 mouse model of Alzheimer's disease by in vivo electron paramagnetic resonance imaging.

Alzheimer's disease (AD) is a common neurodegenerative disease that causes progressive cognitive decline. Deposition of amyloid-β (Aβ) peptides is the most important pathophysiological hallmark of AD. Oxidative stress induced by the generation of reactive oxygen species (ROS) is a prominent phenomenon in AD and is known to occur early in its course.

Clinicopathologic Features of Oculopharyngodistal Myopathy With LRP12 CGG Repeat Expansions Compared With Other Oculopharyngodistal Myopathy Subtypes.

Importance: Repeat expansion of CGG in LRP12 has been identified as the causative variation of oculopharyngodistal myopathy (OPDM). However, to our knowledge, the clinicopathologic features of OPDM with CGG repeat expansion in LRP12 (hereafter referred to as OPDM_LRP12) remain unknown.

Objective: To identify and characterize the clinicopathologic features of patients with OPDM_LRP12.

[A case of Charcot-Marie-Tooth disease type 2Z caused by MORC2 S87L mutation mimicking spinal muscular atrophy].

A 33-year-old man with an unremarkable family history has had limb muscle weakness, joint contracture and skeleton deformation from early childhood. He was diagnosed with spinal muscular atrophy (SMA) by a pediatrician. He needed assistance and used orthoses in his daily life.

Multiple system atrophy in Hokkaido, Japan: a prospective registry study of natural history and symptom assessment scales followed for 5 years.

Objectives: Multiple system atrophy (MSA) is a refractory neurodegenerative disease, but novel treatments are anticipated. An accurate natural history of MSA is important for clinical trials, but is insufficient. This regional registry was launched to complement clinical information on MSA.

SIRT1 decelerates morphological processing of oligodendrocyte cell lines and regulates the expression of cytoskeleton-related oligodendrocyte proteins.

SIRT1 is involved in the regulation of a variety of biological processes such as metabolism, stress response, autophagy and differentiation. Although progenitor cells of oligodendrocytes (OPCs) express high level of SIRT1, its function on differentiation is unknown. Because we have shown that SIRT1 plays a pivotal role in differentiation of neural precursor cells, we hypothesized that SIRT1 may also participate in the differentiation of oligodendrocytes (OLGs).

Sporadic Amyotrophic Lateral Sclerosis Due to a FUS P525L Mutation with Asymmetric Muscle Weakness and Anti-ganglioside Antibodies.

Amyotrophic lateral sclerosis (ALS) due to a fused in sarcoma (FUS) P525L mutation is characterized by a rapidly progressive course. Multifocal motor neuropathy (MMN) may resemble ALS in early stage and is associated with anti-ganglioside antibodies. A 38-year-old woman was admitted to our hospital because of progressive muscle weakness in the right limbs.

[A case of facial-onset sensory and motor neuronopathy (FOSMN) with cerebellar ataxia and abnormal decrement in repetitive nerve stimulation test].

A 59-year-old woman presented with a 7-year history of facial numbness on the left side, and gradual worsening of symptoms. Over several years, facial muscle weakness, dysarthria, tongue atrophy and fasciculation had progressed. Then, she developed cerebellar ataxia affecting the left extremities, in addition to earlier symptoms.

HLA genotype-clinical phenotype correlations in multiple sclerosis and neuromyelitis optica spectrum disorders based on Japan MS/NMOSD Biobank data.

HLA genotype-clinical phenotype correlations are not established for multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). We studied HLA-DRB1/DPB1 genotype-phenotype correlations in 528 MS and 165 NMOSD cases using Japan MS/NMOSD Biobank materials. HLA-DRB1*04:05, DRB1*15:01 and DPB1*03:01 correlated with MS susceptibility and DRB1*01:01, DRB1*09:01, DRB1*13:02 and DPB1*04:01 were protective against MS.

Streptococcus oralis Meningitis with Gingival Bleeding in a Patient: A Case Report and Review of the Literature.

An 81-year-old man with a history of gingival bleeding presented with a fever, headache, and drowsiness. His mouth and full dentures were unsanitary. Laboratory tests revealed Streptococcus oralis meningitis caused by odontogenic bacteremia.

Hyperemesis-induced Wernicke-Korsakoff Syndrome due to Hypergastrinemia during Long-term Treatment with Proton Pump Inhibitors.

We herein report a patient with Wernicke-Korsakoff syndrome (WKS) who had neither a history of alcoholism or of history of gastric surgery. A 56-year-old woman was transferred to our hospital because of the loss of consciousness and she was diagnosed to have Wernicke encephalopathy. She showed proton pump inhibitor-induced refractory hypergastrinemia with the subsequent development of hyperemesis and a vitamin B1 deficiency.

[Unilateral ptosis induced by pure midbrain infarction: a case report].

We describe herein a case with left-side ptosis induced by pure midbrain infarction in a 49-year-old woman. She also presented with diplopia and right-side cerebellar ataxia. MRI demonstrated new ischemic stroke of the left ventral paramedian midbrain.

Mouse Bone Marrow-derived Microglia-like Cells Secrete Transforming Growth Factor-β1 and Promote Microglial Aβ Phagocytosis and Reduction of Brain Aβ.

Accumulation of amyloid-β (Aβ) in brain tissue contributes to the pathophysiology of Alzheimer's disease (AD). We recently reported that intrahippocampal transplantation of mouse bone marrow-derived microglia-like (BMDML) cells suppresses brain amyloid pathology and cognitive impairment in a mouse model of AD. How these transplanted cells interact with resident microglia remains unknown.

Successful intervention for overwhelming postsplenectomy infection caused by non-vaccine pneumococcal serotype 23A.

The spleen plays an important role in the body's immune defense against invasive infections, particularly those caused by encapsulated bacteria. Encapsulated bacterial infection in asplenic patients is a medical emergency called overwhelming postsplenectomy infection (OPSI) and has a mortality rate of 50-70%. Here, we report the case of a 51-year-old Asian man who complained of emesis and diarrhea as primary symptoms.