FYVE-type zinc finger-containing phosphoinositide kinase (PIKFYVE), which is essential for phosphatidylinositol 3,5-bisphosphate [PtdIns(3,5)P2] production, is an important regulator of lysosomal homeostasis. PIKFYVE dysfunction leads to cytoplasmic vacuolization; however, the underlying mechanism remains unknown. In this study, we explored the cause of vacuole enlargement upon PIKFYVE inhibition in DU145 prostate cancer cells.
View Article and Find Full Text PDFMed Mol Morphol
November 2024
Dry eye, a common ocular surface disease associated with tear film instability and corneal impairment, is frequently accompanied by ocular discomfort and pain. Recent research has shown that corneal nerve dysfunction may play a role in certain pathologies of dry eye; however, the details remain unclear. To clarify the aberration in corneal nerves underlying sensory abnormalities, in addition to corneal impairment in dry eye, we examined the morphological alterations of nerve fibers in the corneas excised from guinea pigs with dry eye, where the lacrimal glands were surgically excised.
View Article and Find Full Text PDFPainless thyroiditis, which is rare in children, exhibits the characteristic sequence of hyperthyroidism, including aggressive and disruptive behaviors. Unlike subacute thyroiditis or Graves' disease, painless thyroiditis is challenging to diagnose because of its mild symptoms and minimal or absent physical findings. Moreover, aggressive and disruptive behaviors in children with psychiatric disorders may be misconstrued as exacerbation of underlying symptoms.
View Article and Find Full Text PDFPurpose: Sensory nerve terminals are highly distributed in the cornea, and regulate ocular surface sensation and homeostasis in response to various endogenous and exogenous stimuli. However, little is known about mediators regulating the physiological and pathophysiological activities of corneal sensory nerves. The aim of this study was to investigate the presence of cholinergic regulation in sensory nerves in the cornea.
View Article and Find Full Text PDFBackground: To prevent stroke recurrence, a superficial temporal artery-middle cerebral artery (STA-MCA) bypass for atherosclerotic cerebrovascular occlusive disease is performed. Post stroke epilepsy is known as serious sequelae of stroke. Herein, we present a case of a 60-year-old man who underwent STA-MCA bypass for the prevention of stroke recurrence; however, the donor artery was deemed to be temporally occluded secondary to generalized seizure.
View Article and Find Full Text PDFObjective: Neurosurgeons occasionally encounter cases of subarachnoid hemorrhage (SAH) in admitted walk-in patients, termed "walk-in SAH." However, their clinical characteristics have not been fully understood. We thus, aimed to investigate several characteristics of patients with walk-in SAH and compare them with those of patients with good grade SAH who arrived at the hospital by ambulance.
View Article and Find Full Text PDFHow is the quantal size in neurotransmitter release adjusted for various firing levels? We explored the possible mechanisms that regulate acetylcholine (ACh) release from cholinergic interneurons using an ultra-mini superfusion system. After preloading [ H]ACh in rat striatal cholinergic interneurons, the release was elicited by electrical stimulation under a condition in which presynaptic cholinergic and dopaminergic feedback was inhibited. [ H]ACh release was reproducible at intervals of more than 10 min; shorter intervals resulted in reduced levels of ACh release.
View Article and Find Full Text PDFInflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, is an intestinal disorder that causes prolonged inflammation of the gastrointestinal tract. Currently, the etiology of IBD is not fully understood and treatments are insufficient to completely cure the disease. In addition to absorbing essential nutrients, intestinal epithelial cells prevent the entry of foreign antigens (micro-organisms and undigested food) through mucus secretion and epithelial barrier formation.
View Article and Find Full Text PDFIt has been known that a number of tyrosine hydroxylase (TH)-positive neurons, which are regarded as dopaminergic (DA) neurons, exist in the dorsal raphe (DR). These DA neurons in the DR and periaqueductal gray (PAG) region (DA neurons) are thought to belong to the A10 cluster, which is known to be heterogeneous. This DA population projects to the central nucleus of the amygdala (CeA) and the bed nucleus of the stria terminalis (BNST) and has been reported to modulate various affective behaviors.
View Article and Find Full Text PDFFront Behav Neurosci
September 2022
Recent clinical studies indicate that dry eye is closely associated with psychiatric disorders such as depression and anxiety. Here, we investigated whether two types of mouse dry eye models showed depressive-like behavior in forced swim and sucrose preference tests, and whether voluntary wheel-running helped ameliorate depressive states. To reproduce the dry eye models, the exorbital lacrimal glands (ELG) or exorbital and intraorbital lacrimal glands (ELG+ILG) were bilaterally excised from male C57BL/6J mice.
View Article and Find Full Text PDFCholinergic transmission underlies higher brain functions such as cognition and movement. To elucidate the process whereby acetylcholine (ACh) release is maintained and regulated in the central nervous system, uptake of [ H]choline and subsequent synthesis and release of [ H]ACh were investigated in rat striatal segments. Incubation with [ H]choline elicited efficient uptake via high-affinity choline transporter-1, resulting in accumulation of [ H]choline and [ H]ACh.
View Article and Find Full Text PDFThis study aimed to investigate how atherosclerosis affects the soluble guanylate cyclase (sGC) system in coronary arteries. Rabbits were fed a normal diet for 12 weeks (N group) or a diet containing high cholesterol (1%) for 4 weeks (S-HC group) and 12 weeks (L-HC group). Cholesterol deposition in the intima of coronary arteries was observed in the S-HC group, but the formation of an atherosclerotic plaque was not observed.
View Article and Find Full Text PDFChronic tear deficiency enhances the excitability of corneal cold-sensitive nerves that detect ocular dryness, which can lead to discomfort in patients with dry eye disease (DED). However, changes in corneal nerve excitations through the polymodal nociceptor "transient receptor potential vanilloid 1" (TRPV1) and the potential link between this receptor and symptoms of DED remain unclear. In this study, we examined the firing properties of corneal cold-sensitive nerves expressing TRPV1 and possible contributions of chronic tear deficiency to corneal nerve excitability by TRPV1 activation.
View Article and Find Full Text PDFBackground: Complications of cranial distraction techniques can arise perioperatively. This study assessed long-term clinical outcomes following cranial distraction for craniosynostosis. We analyzed factors involved in those complications.
View Article and Find Full Text PDFBackground: In craniosynostosis patients under 3 months of age, suturectomy is a valuable early treatment improving their outcomes. However, conventional suturectomy might not be in severe patients. The efficacy of our developed suturectomy using absorbable plates was examined.
View Article and Find Full Text PDFBackground And Purpose: Glutamate and metabotropic glutamate (mGlu) receptors on primary sensory neurons are crucial in modulating pain sensitivity. However, it is unclear how inflammation affects mGlu receptor-mediated nociceptive responses. We therefore investigated the effects of mGlu receptor agonists on pain-related behaviour during persistent inflammation and their underlying mechanisms.
View Article and Find Full Text PDFElectroconvulsive therapy (ECT) is an effective treatment for major depression. Previous studies suggested that dopaminergic neurotransmission plays a crucial role in the mechanism of the action of ECT. Since dopamine transporters (DAT) regulate extracellular dopamine concentration, DAT represents an interesting target for the study of the mechanism of action of ECT.
View Article and Find Full Text PDFAim: Dysfunction of dopaminergic neurons in the central nervous system is considered to be related to major depressive disorder (MDD). Especially, MDD in geriatric patients is characterized by anhedonia, which is assumed to be associated with reduced dopamine neurotransmission in the reward system. Dopamine transporter (DAT) is considered to reflect the function of the dopamine nerve system.
View Article and Find Full Text PDFBackground: Beetroot has attracted much attention because of its blood pressure-lowering properties. Although beetroot contains various nutritional compounds, including inorganic nitrate, some of their physiological properties are not fully understood. In this study, we examined whether betanin, a beetroot component, has a regulatory effect on vascular tone.
View Article and Find Full Text PDFCigarette smoking induces vascular endothelial dysfunction characterized by impaired nitric oxide (NO) bioavailability. There are two types of soluble guanylate cyclase (sGC), which is a cellular target of NO: NO-sensitive reduced form (the heme moiety with a ferrous iron) and NO-insensitive oxidized (the heme moiety with a ferric iron)/heme-free form. This study investigated the influence of cigarette smoking on NO-sensitive and NO-insensitive sGC-mediated vascular tone regulation in organ chamber experiments with isolated rat and human arteries.
View Article and Find Full Text PDFBackground/aims: Soluble guanylate cyclase (sGC) exists as reduced, oxidized, and heme-free forms. Currently, it is unclear whether endovascular mechanical stenosis has an impact on vascular tone control by drugs targeting sGC, namely cGMP generators.
Methods: Pharmacological responses to acidified sodium nitrite (reduced sGC stimulant) and BAY 60-2770 (oxidized/heme-free sGC stimulant) were studied in balloon-injured rat carotid arteries at several time points.
This study investigated the effects of thiol and heme oxidants on responsiveness to cGMP generators in isolated rat aorta and pulmonary artery using an organ chamber. The nitric oxide (NO) donor sodium nitroprusside (SNP)-induced relaxation was impaired by exposure to the thiol oxidant diamide in both the aorta and the pulmonary artery, whereas the soluble guanylate cyclase (sGC) stimulator BAY 41-2272- or the sGC activator BAY 60-2770-induced relaxation was not affected. The impairment by diamide of SNP-induced aortic and pulmonary arterial relaxation was completely restored by post-treatment with the thiol reductant dithiothreitol.
View Article and Find Full Text PDFRegulation of neurotransmitter release in the central nervous system is complex. Here, we investigated regulatory mechanisms for acetylcholine (ACh) release from cholinergic neurons by performing superfusion experiments with rat striatal segments after labelling the cellular ACh pool with [ H]choline. Electrical stimulation-evoked pronounced [ H]ACh release from cholinergic neurons.
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