ABSTRACT
Cholinergic activation can enhance glutamatergic activity in the hippocampus under pathologic conditions, such as Alzheimer's disease. The aim of the present study was to elucidate the relationship between glutamatergic neural functional decline and cholinergic neural dysfunction in the hippocampus. We report the importance of hippocampal cholinergic neurostimulating peptide (HCNP) in inducing acetylcholine synthesis in the medial septal nucleus. Here, we demonstrate that HCNP-precursor protein (pp) knockout (KO) mice electrophysiologically presented with glutamatergic dysfunction in the hippocampus with age. The impairment of cholinergic function via a decrease in vesicular acetylcholine transporter in the pre-synapse with reactive upregulation of the muscarinic M1 receptor may be partly involved in glutamatergic dysfunction in the hippocampus of HCNP-pp KO mice. The results, in combination with our previous reports that show the reduction of hippocampal theta power through a decrease of a region-specific choline acetyltransferase in the stratum oriens of CA1 and the decrease of acetylcholine concentration in the hippocampus, may indicate the defined cholinergic dysfunction in HCNP-pp KO mice. This may also support that HCNP-pp KO mice are appropriate genetic models for cholinergic functional impairment in septo-hippocampal interactions. Therefore, according to the cholinergic hypothesis, the model mice might are potential partial pathological animal models for Alzheimer's disease.
Subject(s)
Alzheimer Disease , Phosphatidylethanolamine Binding Protein , Mice , Animals , Mice, Knockout , Phosphatidylethanolamine Binding Protein/genetics , Alzheimer Disease/metabolism , Acetylcholine/metabolism , Hippocampus/metabolism , Cholinergic Agents/metabolismABSTRACT
The cholinergic efferent network from the medial septal nucleus to the hippocampus plays an important role in learning and memory processes. This cholinergic projection can generate theta oscillations in the hippocampus to encode novel information. Hippocampal cholinergic neurostimulating peptide (HCNP), which induces acetylcholine (Ach) synthesis in the medial septal nuclei of an explant culture system, was purified from the soluble fraction of postnatal rat hippocampus. HCNP is processed from the N-terminal region of a 186-amino acid, 21-kDa HCNP precursor protein, also known as Raf kinase inhibitory protein and phosphatidylethanolamine-binding protein 1. Here, we confirmed direct reduction of Ach release in the hippocampus of freely moving HCNP-pp knockout mice under an arousal state by the microdialysis method. The levels of vesicular acetylcholine transporter were also decreased in the hippocampus of these mice in comparison with those in control mice, suggesting there was decreased incorporation of Ach into the synaptic vesicle. These results potently indicate that HCNP may be a cholinergic regulator in the septo-hippocampal network.
Subject(s)
Acetylcholine/metabolism , Hippocampus/metabolism , Phosphatidylethanolamine Binding Protein/metabolism , Animals , Female , Mice, Knockout , Phosphatidylethanolamine Binding Protein/genetics , Vesicular Acetylcholine Transport Proteins/metabolismABSTRACT
Cholinergic neural activation from the medial septal nucleus to hippocampus plays a crucial role in episodic memory as a regulating system for glutamatergic neural activation in the hippocampus. As a candidate regulating factor for acetylcholine synthesis in the medial septal nucleus, hippocampal cholinergic neurostimulating peptide (HCNP) was purified from the soluble fraction of young adult rat hippocampus. HCNP is released from its precursor protein (HCNP-pp), also referred to as phosphatidylethanolamine-binding protein 1. We recently reported that HCNP-pp conditional knockout (KO) mice, in which the HCNP-pp gene was knocked out at 3 months of age by tamoxifen injection, display no significant behavioral abnormalities, whereas HCNP-pp KO mice have a diminished cholinergic projection to CA1 and a decreased of theta activity in CA1. In this study, to address whether HCNP-pp reduction in early life is associated with behavioral changes, we evaluated the behavior of HCNP-pp KO mice in which HCNP-pp was downregulated from an early phase (postnatal days 14-28). As unexpected, HCNP-pp KO mice had no behavioral deficits. However, a significant positive correlation between HCNP-pp and gamma-aminobutyric acid A (GABAA) receptor α3 subunit mRNA expression was found in individuals. This finding suggests involvement of HCNP-pp in regulating GABAA receptor α3 gene expression.
ABSTRACT
Sexual intercourse is known as one of the daily activities triggering spontaneous cervicocephalic artery dissection (sCAD), however, it has been unclear if masturbation can trigger the development of sCAD. Herein, we report a case of sCAD in association with masturbation. A 51-year-old right-handed man developed subarachnoid hemorrhage during masturbation. The dissection of the left internal carotid artery was evident on the 9th hospital day. Finally, he was treated with stenting and coiling and discharged with a good prognosis.
Subject(s)
Carotid Artery, Internal, Dissection/etiology , Masturbation/complications , Subarachnoid Hemorrhage/etiology , Carotid Artery, Internal, Dissection/diagnostic imaging , Carotid Artery, Internal, Dissection/therapy , Endovascular Procedures/instrumentation , Humans , Male , Middle Aged , Stents , Subarachnoid Hemorrhage/diagnostic imaging , Subarachnoid Hemorrhage/therapy , Treatment OutcomeSubject(s)
Anti-N-Methyl-D-Aspartate Receptor Encephalitis/therapy , Autoantibodies/blood , Autoimmune Diseases of the Nervous System/therapy , Encephalitis/therapy , Immunoglobulins, Intravenous/therapeutic use , Thyroid Gland/immunology , Aged , Autoantibodies/administration & dosage , Encephalitis/diagnosis , Encephalitis/etiology , Encephalitis/immunology , Female , Graves Disease/immunology , Graves Disease/therapy , Hashimoto Disease/diagnosis , Hashimoto Disease/etiology , Hashimoto Disease/immunology , Humans , Male , Young AdultABSTRACT
BACKGROUND/AIMS: Sulfation is considered to be a detoxifying mechanism for bile acids, which allows the sulfated bile acids to be eliminated in the urine (urinary sulfated bile acids: USBA) by enhancing renal clearance when serum bile acids increase due to hepatobiliary disease. We measured urinary sulfated bile acids in patients positive for hepatitis C virus and studied the relation between USBA and standard liver function tests. METHODOLOGY: Seventy-eight outpatients could be followed for at least one year were enrolled in this study. Blood and urine samples were simultaneously obtained from the patients. The measured urinary sulfated bile acids levels were adjusted for the urinary creatinine concentration and the normal value was defined <8 micromol/g creatinine. RESULTS: Among the 78 patients, the mean USBA level of 26 carriers, 37 patients with chronic hepatitis C, 9 with liver cirrhosis, and 6 with hepatocellular carcinoma were 6.0 +/- 6.1 micromol/g creatinine (mean +/- SD), 27.9 +/- 35.8, 33.1+/- 22.7, and 50.6 +/- 47.3, respectively. The mean urinary sulfated bile acids level was correlated with the clinical progression of these liver diseases. CONCLUSIONS: Urinary sulfated bile acids are considered to be a useful diagnostic indicator of impaired liver function, and can also be used to assess the severity of hepatic disease.
Subject(s)
Bile Acids and Salts/urine , Hepatitis C/urine , Adult , Aged , Circadian Rhythm , Female , Humans , Liver Function Tests , Male , Middle Aged , Statistics, NonparametricABSTRACT
A spiropyran derivative (1) behaves as a selective and sensitive cyanide anion receptor in aqueous media under UV irradiation. The receptor can be reproduced just by irradiation with visible light.
Subject(s)
Anions/analysis , Benzopyrans/chemistry , Cyanides/analysis , Environmental Monitoring/methods , Indoles/chemistry , Nitro Compounds/chemistry , Cyanides/chemistry , Photochemical Processes , Ultraviolet RaysABSTRACT
AIMS: To determine the cut-off level of endometrial thickness for detecting endometrial disease on a large scale of screening and to examine the usefulness of transvaginal ultrasonography (TVS) for endometrial disease screening in asymptomatic postmenopausal Japanese women. METHODS: The study involved 1,400 postmenopausal women in whom endometrial thickness was measured with TVS, and then compared with the histopathological diagnosis of endometrial specimens. RESULTS: The prevalence of endometrial disease in asymptomatic and symptomatic cases was 2.3 and 21%. In symptomatic cases, at a cut-off limit of 3 mm for endometrial thickness, the sensitivity for detecting endometrial disease was 94%, specificity 70% and positive predictive value 46%. With an endometrial thickness < or = 3 mm, the probability that endometrial disease would be overlooked was 0.025. In asymptomatic cases, the corresponding figures at a cut-off limit of 3 mm were 90, 84, 12% and 0.003. CONCLUSIONS: TVS does not appear to be an effective screening method in asymptomatic postmenopausal Japanese women because of the low prevalence of endometrial disease in this population. We recommend a normal cut-off level for endometrial thickness of 4 mm in symptomatic postmenopausal Japanese women.
Subject(s)
Endometrium/diagnostic imaging , Postmenopause , Adult , Aged , Endometrium/pathology , Female , Humans , Japan/epidemiology , Mass Screening , Middle Aged , Prospective Studies , Sensitivity and Specificity , Ultrasonography , Uterine Diseases/diagnostic imaging , Uterine Diseases/epidemiologyABSTRACT
OBJECTIVE: To evaluate 3 methods for measuring urine bile acids (UBA) and compare their diagnostic performance with that of the serum bile acids (SBA) test and other routine screening tests in dogs with hepatic disorders. DESIGN: Prospective study. ANIMALS: 15 healthy dogs, 102 dogs with hepatic disorders, and 9 dogs with clinical signs of hepatic disorders that were found to have nonhepatic disorders. PROCEDURES: Blood and urine samples were collected from sick dogs and healthy dogs for serum biochemical analyses, and determination of concentrations of SBA and UBA. Urine samples were obtained from 15 healthy dogs to establish an upper cutoff value for UBA concentrations. The UBA were measured by use of a quantitative-linked enzymatic colorimetric method. Three analytical modifications were evaluated; 1 quantified only urine sulfated bile acids (USBA), 1 only urine nonsulfated bile acids (UNSBA), and 1 quantified both (USBA plus UNSBA). The UBA values were standardized with the urine creatinine concentration. RESULTS: The UNSBA-to-creatinine ratio and USBA plus UNSBA-to-creatinine ratio tests had the best diagnostic performance of the UBA tests; each had a substantially higher specificity, slightly higher positive predictive value, slightly lower negative predictive value, and lower sensitivity than the SBA test. These UBA-to-creatinine values were positively correlated with SBA values. The USBA-to-creatinine ratio had poor sensitivity, indicating a low rate of bile acid sulfation in dogs. CONCLUSIONS AND CLINICAL RELEVANCE: The UBA can be measured in dogs with sufficient repeatability and accuracy for clinical application. The UNSBA-to-creatinine ratio and USBA plus UNSBA-to-creatinine ratio identified dogs with hepatic disorders nearly as well as the SBA test.