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1.
Rev. colomb. psiquiatr ; 48(2): 127-130, ene.-jun. 2019. tab
Article in Spanish | LILACS, COLNAL | ID: biblio-1042855

ABSTRACT

RESUMEN La encefalitis asociada a anticuerpos contra el receptor de N-metil-D-Aspartato (NMDAr) es una entidad clínica recientemente descrita con un número creciente de casos reporta dos. Los síntomas psiquiátricos en etapas tempranas de la enfermedad conforman un reto diagnóstico para el médico tratante. Presentamos dos casos clínicos: el caso clínico 1, un hombre de 26 arios y el caso clínico 2, un joven de 18 arios, ambos abordados como primer episodio de psicosis y hospitalizados en instituciones psiquiátricas. Posteriormente, ambos casos fueron diagnosticados como encefalitis anti-NMDAr. La alta prevalencia de síntomas psiquiátricos en la encefalis anti-NMDAr demanda a los médicos psiquiatras y neurólogos a tener un alto índice de sospecha en presencia de síntomas atípicos en pacientes evaluados por primer episodio de psicosis.


ABSTRACT Anti-N-methyl-D-Aspartate receptor (NMDAr) encephalitis is a recently described clinical entity with an increasing number of reported cases. Psychiatric symptoms in the early stages of the disease constitute a diagnostic challenge for the treating physician. We present two clinical cases: clinical case 1, a 26-year-old man, and clinical case 2, an 18-year-old man; both presented with a first episode of psychosis and were hospitalized as psychiatric disorders. Subsequently, both cases were diagnosed as anti-NMDAr encephalitis. The high prevalence of psychiatric symptoms in anti-NMDAr encephalitis forces psychiatrists and neurologists to have a high degree of suspicion in the presence of atypical symptoms in patients evaluated for the first episode of psychosis.


Subject(s)
Humans , Male , Adult , Psychotic Disorders , Anti-N-Methyl-D-Aspartate Receptor Encephalitis , Psychiatry , N-Methylaspartate , Emblems and Insignia , Encephalitis , Neurologists , Mental Disorders , Antibodies
2.
Experimental Neurobiology ; : 495-503, 2019.
Article in English | WPRIM | ID: wpr-763778

ABSTRACT

Memantine, a noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) receptor, suppresses the release of excessive levels of glutamate that may induce neuronal excitation. Here we investigated the effects of memantine on salicylate-induced tinnitus model. The expressions of the activity-regulated cytoskeleton-associated protein (ARC) and tumor necrosis factor-alpha (TNF α)genes; as well as the NMDA receptor subunit 2B (NR2B) gene and protein, were examined in the SH-SY5Y cells and the animal model. We also used gap-prepulse inhibition of the acoustic startle reflex (GPIAS) and noise burst prepulse inhibition of acoustic startle, and the auditory brainstem level (electrophysiological recordings of auditory brainstem responses, ABR) and NR2B expression level in the auditory cortex to evaluate whether memantine could reduce salicylate-mediated behavioral disturbances. NR2B was significantly upregulated in salicylate-treated cells, but downregulated after memantine treatment. Similarly, expression of the inflammatory cytokine genes TNFα and immediate-early gene ARC was significantly increased in the salicylate-treated cells, and decreased when the cells were treated with memantine. These results were confirmed by NR2B immunocytochemistry. GPIAS was attenuated to a significantly lesser extent in rats treated with a combination of salicylate and memantine than in those treated with salicylate only. The mean ABR threshold in both groups was not significant different before and 1 day after the end of treatment. Additionally, NR2B protein expression in the auditory cortex was markedly increased in the salicylate-treated group, whereas it was reduced in the memantine-treated group. These results indicate that memantine is useful for the treatment of salicylate-induced tinnitus.


Subject(s)
Acoustics , Animals , Auditory Cortex , Brain Stem , Evoked Potentials, Auditory, Brain Stem , Genes, Immediate-Early , Glutamic Acid , Immunohistochemistry , Integrin alpha2 , Memantine , Models, Animal , N-Methylaspartate , Neurons , Noise , Prepulse Inhibition , Rats , Reflex, Startle , Tinnitus , Tumor Necrosis Factor-alpha
3.
Experimental Neurobiology ; : 516-528, 2019.
Article in English | WPRIM | ID: wpr-763776

ABSTRACT

We have previously demonstrated that the neurosteroid dehydroepiandrosterone sulfate (DHEAS) induces functional potentiation of N-methyl-D-aspartate (NMDA) receptors via increases in phosphorylation of NMDA receptor GluN1 subunit (pGluN1). However, the modulatory mechanisms responsible for the expression of the DHEA-synthesizing enzyme, cytochrome P450c17 following peripheral nerve injury have yet to be examined. Here we determined whether oxidative stress induced by the spinal activation of nitric oxide synthase type II (NOS-II) modulates the expression of P450c17 and whether this process contributes to the development of neuropathic pain in rats. Chronic constriction injury (CCI) of the sciatic nerve induced a significant increase in the expression of NOS-II in microglial cells and NO levels in the lumbar spinal cord dorsal horn at postoperative day 5. Intrathecal administration of the NOS-II inhibitor, L-NIL during the induction phase of neuropathic pain (postoperative days 0~5) significantly reduced the CCI-induced development of mechanical allodynia and thermal hyperalgesia. Sciatic nerve injury increased the expression of PKC- and PKA-dependent pGluN1 as well as the mRNA and protein levels of P450c17 in the spinal cord at postoperative day 5, and these increases were suppressed by repeated administration of L-NIL. Co-administration of DHEAS together with L-NIL restored the development of neuropathic pain and pGluN1 that were originally inhibited by L-NIL administration alone. Collectively these results provide strong support for the hypothesis that activation of NOS-II increases the mRNA and protein levels of P450c17 in the spinal cord, ultimately leading to the development of central sensitization and neuropathic pain induced by peripheral nerve injury.


Subject(s)
Animals , Central Nervous System Sensitization , Constriction , Cytochromes , Dehydroepiandrosterone , Dehydroepiandrosterone Sulfate , Hyperalgesia , N-Methylaspartate , Neuralgia , Nitric Oxide Synthase Type II , Nitric Oxide Synthase , Nitric Oxide , Oxidative Stress , Peripheral Nerve Injuries , Phosphorylation , Rats , RNA, Messenger , Rodentia , Sciatic Nerve , Spinal Cord , Spinal Cord Dorsal Horn
4.
Experimental Neurobiology ; : 529-536, 2019.
Article in English | WPRIM | ID: wpr-763775

ABSTRACT

Stress can induce a serious epileptic encephalopathy that occurs during early infancy. Recent studies have revealed that prenatal stress exposure is a risk factor for the development of infantile spasms. Our previous work demonstrates that prenatal stress with betamethasone-induced alterations to the expression of the K⁺/Cl⁻ co-transporter (KCC2) in gamma-aminobutyric acid (GABA) interneurons lowers the seizure threshold in exposed animals. Here, we further investigated the mechanisms involved in this KCC2 dysfunction and explored possible treatment options. We stressed Sprague-Dawley rats prenatally and further treated dams with betamethasone on gestational day 15, which increases seizure susceptibility and NMDA (N-Methyl-D-aspartate)-triggered spasms on postnatal day 15. In this animal model, first, we evaluated baseline calpain activity. Second, we examined the cleavage and dephosphorylation of KCC2. Finally, we checked the effect of a calpain inhibitor on seizure occurrence. The phosphorylated-N-methyl-D-aspartate Receptor 2B (NR2B):non-phosphorylated NR2B ratio was found to be higher in the cortex of the prenatally stressed beta-methasone model. We further found that the betamethasone model exhibited increased phosphorylation of calpain-2 and decreased phosphorylation of KCC2 and Glutamic acid decarboxylase 67 (GAD67). After using a calpain inhibitor in prenatal-stress rats, the seizure frequency decreased, while latency increased. GABAergic depolarization was further normalized in prenatal-stress rats treated with the calpain inhibitor. Our study suggests that calpain-dependent cleavage and dephosphorylation of KCC2 decreased the seizure threshold of rats under prenatal stress. Calpain-2 functions might, thus, be targeted in the future for the development of treatments for epileptic spasms.


Subject(s)
Animals , Betamethasone , Brain Diseases , Calpain , Epilepsy , gamma-Aminobutyric Acid , Glutamate Decarboxylase , Humans , Infant , Infant, Newborn , Interneurons , Models, Animal , N-Methylaspartate , Phosphorylation , Rats , Rats, Sprague-Dawley , Risk Factors , Seizures , Spasm , Spasms, Infantile
5.
Experimental Neurobiology ; : 390-403, 2019.
Article in English | WPRIM | ID: wpr-763766

ABSTRACT

Memantine is a non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist clinically approved for moderate-to-severe Alzheimer's disease (AD) to improve cognitive functions. There is no report about the proteomic alterations induced by memantine in AD mouse model yet. In this study, we investigated the protein profiles in the hippocampus and the cerebral cortex of AD-related transgenic mouse model (3×Tg-AD) treated with memantine. Mice (8-month) were treated with memantine (5 mg/kg/bid) for 4 months followed by behavioral and molecular evaluation. Using step-down passive avoidance (SDA) test, novel object recognition (NOR) test and Morris water maze (MWM) test, it was observed that memantine significantly improved learning and memory retention in 3xTg-AD mice. By using quantitative proteomic analysis, 3301 and 3140 proteins in the hippocampus and the cerebral cortex respectively were identified to be associated with AD abnormalities. In the hippocampus, memantine significantly altered the expression levels of 233 proteins, among which PCNT, ATAXIN2, TNIK, and NOL3 were up-regulated, and FLNA, MARK 2 and BRAF were down-regulated. In the cerebral cortex, memantine significantly altered the expression levels of 342 proteins, among which PCNT, PMPCB, CRK, and MBP were up-regulated, and DNM2, BRAF, TAGLN 2 and FRY1 were down-regulated. Further analysis with bioinformatics showed that memantine modulated biological pathways associated with cytoskeleton and ErbB signaling in the hippocampus, and modulated biological pathways associated with axon guidance, ribosome, cytoskeleton, calcium and MAPK signaling in the cerebral cortex. Our data indicate that memantine induces higher levels of proteomic alterations in the cerebral cortex than in the hippocampus, suggesting memantine affects various brain regions in different manners. Our study provides a novel view on the complexity of protein responses induced by memantine in the brain of AD.


Subject(s)
Alzheimer Disease , Animals , Axons , Brain , Calcium , Cerebral Cortex , Cognition , Computational Biology , Cytoskeleton , Hippocampus , Learning , Memantine , Memory , Mice , Mice, Transgenic , N-Methylaspartate , Proteome , Ribosomes , Water
6.
Article in Korean | WPRIM | ID: wpr-759852

ABSTRACT

Opioids are important drugs for the management of severe cancer pain without a ceiling effect. However, opioid administration leads to dose-limiting complications including drowsiness, hallucinations, delirium, respiratory depression, cognitive impairment, seizure, myoclonus, and hyperalgesia. Opioid-induced hyperalgesia (OIH) is a paradoxical phenomenon as opioid exposure increases pain sensitivity. Reducing or stopping opioids, opioid rotation, or co-administration of N-methyl-D-aspartate (NMDA) antagonists have been suggested for the management of OIH. In this study, we report two clinical cases of successful management of OIH in cancer pain patients that were treated with opioids.


Subject(s)
Analgesics, Opioid , Cognition Disorders , Delirium , Hallucinations , Humans , Hyperalgesia , Myoclonus , N-Methylaspartate , Pain Management , Respiratory Insufficiency , Seizures , Sleep Stages
7.
Article in English | WPRIM | ID: wpr-761790

ABSTRACT

Hydrogen sulfide is well-known to exhibit anti-inflammatory and cytoprotective activities, and also has protective effects in the liver. This study aimed to examine the protective effect of hydrogen sulfide in rats with hepatic encephalopathy, which was induced by mild bile duct ligation. In this rat model, bile ducts were mildly ligated for 26 days. Rats were treated for the final 5 days with sodium hydrosulfide (NaHS). NaHS (25 µmol/kg), 0.5% sodium carboxymethyl cellulose, or silymarin (100 mg/kg) was administered intraperitoneally once per day for 5 consecutive days. Mild bile duct ligation caused hepatotoxicity and inflammation in rats. Intraperitoneal NaHS administration reduced levels of aspartate aminotransferase and alanine aminotransferase, which are indicators of liver disease, compared to levels in the control mild bile duct ligation group. Levels of ammonia, a major causative factor of hepatic encephalopathy, were also significantly decreased. Malondialdehyde, myeloperoxidase, catalase, and tumor necrosis factor-α levels were measured to confirm antioxidative and anti-inflammatory effects. N-Methyl-D-aspartic acid (NMDA) receptors with neurotoxic activity were assessed for subunit NMDA receptor subtype 2B. Based on these data, NaHS is suggested to exhibit hepatoprotective effects and guard against neurotoxicity through antioxidant and anti-inflammatory actions.


Subject(s)
Alanine Transaminase , Ammonia , Animals , Aspartate Aminotransferases , Bile Ducts , Carboxymethylcellulose Sodium , Catalase , Hepatic Encephalopathy , Hydrogen Sulfide , Inflammation , Ligation , Liver , Liver Diseases , Malondialdehyde , Models, Animal , N-Methylaspartate , Necrosis , Peroxidase , Rats , Silymarin , Sodium
8.
Article in English | WPRIM | ID: wpr-739800

ABSTRACT

BACKGROUND: This study investigated the role of NR2B in a modulated pain process in the painful diabetic neuropathy (PDN) rat using various pain stimuli. METHODS: Thirty-two Sprague-Dawley male rats were randomly allocated into four groups (n=8): control, diabetes mellitus (DM) rats and diabetic rats treated with ifenprodil at a lower dose (0.5 µg/day) (I 0.5) or higher dose (1.0 µg/day) (I 1.0). DM was induced by a single injection of streptozotocin at 60 mg/kg on day 0 of experimentation. Diabetic status was assessed on day 3 of the experimentation. The responses on both tactile and thermal stimuli were assessed on day 0 (baseline), day 14 (pre-intervention), and day 22 (post-intervention). Ifenprodil was given intrathecally for 7 days from day 15 until day 21. On day 23, 5% formalin was injected into the rats' hind paw and the nociceptive responses were recorded for 1 hour. The rats were sacrificed 72 hours post-formalin injection and an analysis of the spinal NR2B expression was performed. RESULTS: DM rats showed a significant reduction in pain threshold in response to the tactile and thermal stimuli and higher nociceptive response during the formalin test accompanied by the higher expression of phosphorylated spinal NR2B in both sides of the spinal cord. Ifenprodil treatment for both doses showed anti-allodynic and anti-nociceptive effects with lower expression of phosphorylated and total spinal NR2B. CONCLUSION: We suggest that the pain process in the streptozotocin-induced diabetic rat that has been modulated is associated with the higher phosphorylation of the spinal NR2B expression in the development of PDN, which is similar to other models of neuropathic rats.


Subject(s)
Animals , Diabetes Mellitus , Diabetic Neuropathies , Formaldehyde , Humans , Hyperalgesia , Male , N-Methylaspartate , Pain Measurement , Pain Threshold , Phosphorylation , Rats , Rats, Sprague-Dawley , Receptors, N-Methyl-D-Aspartate , Spinal Cord , Streptozocin
9.
Article in English | WPRIM | ID: wpr-739661

ABSTRACT

Dysregulation of excitatory neurotransmission has been implicated in the pathogenesis of neuropsychiatric disorders. Pharmacological inhibition of N-methyl-D-aspartate (NMDA) receptors is widely used to model neurobehavioral pathologies and underlying mechanisms. There is ample evidence that overstimulation of NMDA-dependent neurotransmission may induce neurobehavioral abnormalities, such as repetitive behaviors and hypersensitization to nociception and cognitive disruption, pharmacological modeling using NMDA has been limited due to the induction of neurotoxicity and blood brain barrier breakdown, especially in young animals. In this study, we examined the effects of intraperitoneal NMDA-administration on nociceptive and repetitive behaviors in ICR mice. Intraperitoneal injection of NMDA induced repetitive grooming and tail biting/licking behaviors in a dose- and age-dependent manner. Nociceptive and repetitive behaviors were more prominent in juvenile mice than adult mice. We did not observe extensive blood brain barrier breakdown or neuronal cell death after peritoneal injection of NMDA, indicating limited neurotoxic effects despite a significant increase in NMDA concentration in the cerebrospinal fluid. These findings suggest that the observed behavioral changes were not mediated by general NMDA toxicity. In the hot plate test, we found that the latency of paw licking and jumping decreased in the NMDA-exposed mice especially in the 75 mg/kg group, suggesting increased nociceptive sensitivity in NMDA-treated animals. Repetitive behaviors and increased pain sensitivity are often comorbid in psychiatric disorders (e.g., autism spectrum disorder). Therefore, the behavioral characteristics of intraperitoneal NMDA-administered mice described herein may be valuable for studying the mechanisms underlying relevant disorders and screening candidate therapeutic molecules.


Subject(s)
Adult , Animals , Autistic Disorder , Blood-Brain Barrier , Cell Death , Cerebrospinal Fluid , Grooming , Humans , Injections, Intraperitoneal , Mass Screening , Mice , Mice, Inbred ICR , N-Methylaspartate , Neurons , Nociception , Pathology , Synaptic Transmission , Tail
10.
Article in English | WPRIM | ID: wpr-763303

ABSTRACT

OBJECTIVES.: Sodium salicylate (SS) is well known for its ototoxic properties that induce functional and morphological changes in the cochlea and brain. Ginkgo biloba extract (GBE) has been widely used for treatment of various neurodegenerative diseases; however, its effects on salicylate-induced ototoxicity remain unclear. Herein, we examined the effects of EGb 761 (EGb), a standard form of GBE, on the plasticity of the N-methyl-D-aspartate receptor subunit 2B (GluN2B) in the inferior colliculus (IC) following SS administration. METHODS.: Seven-week-old Sprague Dawley rats (n=24) were randomly allocated to control, SS, EGb, and EGb+SS groups. The SS group received a single intraperitoneal SS injection (350 mg/kg), the EGb group received EGb orally for 5 consecutive days (40 mg/kg), and the EGb+SS group received EGb for 5 consecutive days, followed by an SS injection. The auditory brainstem responses (ABRs) were assessed at baseline and 2 hours after SS administration. GluN2B expression was examined by Western blot and immunohistochemistry. RESULTS.: There were no significant differences in ABR threshold shifts among the groups. The expression of the GluN2B protein normalized by which of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was significantly lower in the EGb+SS group, as compared to the SS group (P=0.012). Weak and diffused GluN2B immunoreactivity was detected in the IC neural cells of the EGb+SS group, while those of the SS group exhibited strong and diffused GluN2B positivity. CONCLUSION.: EGb may play a role in regulating the GluN2B expression in the IC of salicylate-induced ototoxicity model.


Subject(s)
Blotting, Western , Brain , Cochlea , Evoked Potentials, Auditory, Brain Stem , Ginkgo biloba , Glyceraldehyde 3-Phosphate , Immunohistochemistry , Inferior Colliculi , N-Methylaspartate , Neurodegenerative Diseases , Oxidoreductases , Plastics , Rats, Sprague-Dawley , Sodium Salicylate
11.
Article in English | WPRIM | ID: wpr-759513

ABSTRACT

BACKGROUND: Autism is a challenging neurodevelopmental disorder. Previous clinical observations have suggested altered sedation requirements for children with autism. Our study aimed to test this observation experimentally in an animal model and to explore its possible mechanisms. METHODS: Eight adult pregnant female Sprague-Dawley rats were randomly divided into two groups. Four were injected with intraperitoneal sodium valproate on gestational day 12 and four were injected with normal saline. On postnatal day 28, the newborn male rats were subjected to the open-field test to confirm autistic features. Each rat was injected intraperitoneally with a single dose of propofol (50 mg/kg) or dexmedetomidine (0.2 mg/kg). The times to loss of righting reflex (LORR) and to return of righting reflex (RORR) were recorded. On the following day, all rats were re-sedated and underwent electroencephalography (EEG). Thereafter, the rats were euthanized and their hippocampal gamma-aminobutyric acid type A (GABA(A)) and glutamate N-methyl-D-aspartate (NMDA) receptor gene expressions were assessed. RESULTS: Autistic rats showed significantly longer LORR times and shorter RORR times than did the controls (median LORR times: 12.0 versus 5.0 min for dexmedetomidine and 22.0 versus 8.0 min for propofol; P < 0.05). EEG showed a low-frequency, high-amplitude wave pattern 2 min after LORR in the control rats. Autistic rats showed a high-frequency, low-amplitude awake pattern. Hippocampal GABA(A) receptor gene expression was significantly lower and NMDA gene expression was greater in autistic rats. CONCLUSIONS: This study supports the clinical observations of increased anesthetic sedative requirements in children with autism and our biochemical analyses using and glutamate receptor gene expression highlight possible underlying mechanisms.


Subject(s)
Adult , Animals , Autistic Disorder , Child , Dexmedetomidine , Electroencephalography , Female , gamma-Aminobutyric Acid , Gene Expression , Glutamic Acid , Humans , Infant, Newborn , Male , Models, Animal , N-Methylaspartate , Neurodevelopmental Disorders , Propofol , Rats , Rats, Sprague-Dawley , Receptors, GABA-A , Receptors, Glutamate , Reflex, Righting , Valproic Acid
12.
Experimental Neurobiology ; : 697-708, 2019.
Article in English | WPRIM | ID: wpr-785788

ABSTRACT

Despite some innate limitations, animal models are a potent investigative tool when used to model specific symptoms of a disorder. For example, MK-801, an N-methyl-D-aspartate receptor antagonist, is used as a pharmacological tool to induce symptoms found in some neuropsychiatric disorders. However, a close examination of literature suggests that the application window of MK-801 doses is relatively narrow between individual behavioral paradigms, necessitating careful characterization of the evoked behavioral aberrations and the doses used to induce them. Moreover, variation in behaviors depending on the animal strain, gender of the subject, and the timing of administration is observed, making it difficult to compare the behavioral characteristics reported in different studies. We aim to characterize the behavioral aberrations induced by different doses of MK-801 in CD-1 mice and create a ready reference for future studies. We used CD-1 mice to recapitulate behavioral impairments resulting from acute administration of MK-801. In 0.1 mg kg⁻¹, we observed diminished spontaneous alteration during the Y-maze test, while 0.12 mg kg⁻¹ resulted in hyperlocomotion and social deficit. Mice treated with 0.2 and 0.3 mg kg⁻¹ of MK-801 demonstrated a decreased self-grooming. Finally, all doses significantly impaired cliff avoidance behaviors suggesting increased impulsivity. These results affirm that MK-801 can effectively model various symptoms of different neuropsychiatric disorders in a dose-dependent manner. The observed sensitivity against spatial-memory impairment and impulsive behaviors at low concentration of MK-801 suggest that MK801 may modulate cognitive function and impulsivity in even lower concentration before it can modulate other behavioral domains.


Subject(s)
Animals , Avoidance Learning , Cognition , Dizocilpine Maleate , Impulsive Behavior , Mice , Models, Animal , N-Methylaspartate
13.
Article in Chinese | WPRIM | ID: wpr-690812

ABSTRACT

<p><b>OBJECTIVE</b>To research the central molecular mechanism of gastric motility in functional dyspepsia (FD) rats treated with electroacupuncture (EA) at and points of stomach.</p><p><b>METHODS</b>A total of 30 SD rats were randomized into a blank group, a model group, a Zhongwan+Weishu group, a Weishu group and a Zhongwan group, 6 rats in each group. FD rats were established by moderate clipping tail infuriation and irregular feeding except in the blank group. EA was used at "Zhongwan"(CV 12),"Weishu"(BL 21), and"Zhongwan"(CV 12) +"Weishu"(BL 21) in the corresponding groups for 7 days, once a day, and 20 min a time. No intervention was used in the blank and model groups. Grabbing and fixation were applied in the model group. Gastric antrum motion range and frequency were recorded by gastrointestinal pressure transducer. The expression of subunit NR1 of N-methyl-D-aspartate recepter (NMDAR) in dorsal motor nucleus of the vagus (DMV) was determined by Western blotting. The content of serum nitric oxide (NO) was measured by ELISA.</p><p><b>RESULTS</b>Compared with the blank group, the gastric antrum motion range and NR1 in the DMV decreased and the serum NO content increased in the model group (all <0.05). Compared with the model group, the gastric antrum motion range and NR1 in the DMV increased and the serum NO content decreased in the three EA groups (all <0.05). Compared with the Zhongwan and Weishu groups, the gastric antrum motion range and NR1 in the DMV increased in the Zhongwan + Weishu group (all <0.05). Compared with Zhongwan + Weishu and Zhongwan groups, the expression of NO in the Weishu group decreased (both <0.05). The gastric antrum motion frequency among the 5 groups had no statistical significance (all >0.05).</p><p><b>CONCLUSION</b>EA at the and points can regulate the gastric motility in FD rats which may be by modulating the activity of NMDAR in the central DMV region, thus regulating the serum NO content.</p>


Subject(s)
Acupuncture Points , Animals , Dyspepsia , Therapeutics , Electroacupuncture , Gastrointestinal Motility , N-Methylaspartate , Metabolism , Nitric Oxide , Blood , Random Allocation , Rats , Rats, Sprague-Dawley , Stomach , Vagus Nerve , Metabolism
14.
Article in Korean | WPRIM | ID: wpr-714573

ABSTRACT

Although the biological causes of depression have been well established, the current use of antidepressants are still mostly based on the monoamine hypothesis of depression. However, monoamine antidepressants delay treatment of depression, and there is the problem of depressed patients who are resistant. Ketamine, a N-methyl-D-aspartate receptor (NMDAR) antagonist, is firstly introduced as an anesthetic. The hypothesis on the mechanism of ketamine as an antidepressant has been proposed through direct NMDAR inhibition, inhibition of γ-aminobutyric acid-ergic interneuron NMDARs and the role of ketamine metabolite (2R,6R)-hydroxynorcetamine (HNK). The ketamine also reverses the lack of synaptic connectivity and neurotrophic factors in depressed states by downstream mechanism of action. Through preclinical trials, there is a growing body of evidence indicating that ketamine has the potential for treatment of depression. In recent clinical studies, ketamine exhibits rapid-acting antidepressants effects and improvement of depression and even suicidality. This review examines current researches on molecular and cellular mechanisms of ketamine as an antidepressant, and reviews the current status of clinical studies, problems, and clinical applicability of ketamine.


Subject(s)
Antidepressive Agents , Depression , Glutamic Acid , Humans , Interneurons , Ketamine , N-Methylaspartate , Nerve Growth Factors
15.
Article in English | WPRIM | ID: wpr-714566

ABSTRACT

PURPOSE: Infantile spasms, also known as West syndrome, is an age-specific epileptic seizure. Most patients with this condition also exhibit delayed development. This study aimed to determine the effect of long-term prenatal stress on susceptibility to infantile spasms. METHODS: We subjected pregnant rats to acute or chronic immobilization stress. Resulting offspring received N-methyl-D-aspartic acid (15 mg/kg, intraperitoneally) on postnatal day 15, and their behaviors were observed 75 minutes after injection. The expression of KCC2 and GAD67 was also determined using immunohistochemistry. RESULTS: Exposure to long-term prenatal stress increased the frequency of spasms and decreased the latency to onset of spasms compared with offspring exposed to short-term prenatal stress. Expression of KCC2 and GAD67 also decreased in the group exposed to long-term prenatal stress compared with the group exposed to short-term prenatal stress. CONCLUSION: Our study suggests that exposure to long-term prenatal stress results in increased susceptibility to seizures.


Subject(s)
Animals , Epilepsy , gamma-Aminobutyric Acid , Glutamate Decarboxylase , Humans , Immobilization , Immunohistochemistry , Infant , Infant, Newborn , N-Methylaspartate , Prenatal Exposure Delayed Effects , Rats , Seizures , Spasm , Spasms, Infantile
16.
Article in English | WPRIM | ID: wpr-713586

ABSTRACT

Liquiritigenin (LQ) is a flavonoid that can be isolated from Glycyrrhiza radix. It is frequently used as a tranditional oriental medicine herbal treatment for swelling and injury and for detoxification. However, the effects of LQ on cognitive function have not been fully explored. In this study, we evaluated the memory-enhancing effects of LQ and the underlying mechanisms with a focus on the N-methyl-D-aspartic acid receptor (NMDAR) in mice. Learning and memory ability were evaluated with the Y-maze and passive avoidance tests following administration of LQ. In addition, the expression of NMDAR subunits 1, 2A, and 2B; postsynaptic density-95 (PSD-95); phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII); phosphorylation of extracellular signal-regulated kinase 1/2 (ERK 1/2); and phosphorylation of cAMP response element binding (CREB) proteins were examined by Western blot. In vivo, we found that treatment with LQ significantly improved memory performance in both behavioral tests. In vitro, LQ significantly increased NMDARs in the hippocampus. Furthermore, LQ significantly increased PSD-95 expression as well as CaMKII, ERK, and CREB phosphorylation in the hippocampus. Taken together, our results suggest that LQ has cognition enhancing activities and that these effects are mediated, in part, by activation of the NMDAR and CREB signaling pathways.


Subject(s)
Animals , Behavior Rating Scale , Blotting, Western , Calcium-Calmodulin-Dependent Protein Kinase Type 2 , Cognition , Glycyrrhiza , Hippocampus , In Vitro Techniques , Learning , Medicine, East Asian Traditional , Memory , Mice , N-Methylaspartate , Phosphorylation , Phosphotransferases , Protein Kinases , Receptors, N-Methyl-D-Aspartate , Response Elements
17.
Article in English | WPRIM | ID: wpr-728820

ABSTRACT

PURPOSE: Several studies have shown that magnesium plays an important role in modulating N-methyl-D-aspartate (NMDA)-related seizures by blocking NMDA ion channel receptors. Clinicians usually measure total serum magnesium levels instead of biologically active ionized magnesium levels. We compared the serum ionized magnesium (iMg2+) level between epileptic children with and without a history of fever-triggered seizure (FTS). METHODS: All epileptic children who visited the outpatient clinic or pediatric emergency department at Korea University Guro Hospital between January 2015 and July 2017 were included. Only epileptic children aged 1–8 years who were newly diagnosed within 2 years were included. RESULTS: There were 12 children with FTS and 16 without FTS. Median serum iMg2+ level was 0.93 (0.85–1.14, quartile) mEq/L. Serum iMg2+ level was significantly lower in epileptic children with FTS (0.86 mEq/L) compared to those without FTS (1.10 mEq/L) (P=0.005). No difference was noted in clinical variables between the two groups. Lower serum iMg2+ level significantly increased the risk of having FTS in epileptic children based on multivariable logistic regression analysis (odds ratio [OR]=0.028). CONCLUSION: Serum iMg2+ level was significantly lower in epileptic children with FTS than in those without FTS. Measurement of biologically active serum iMg2+ level could be considered in epileptic children with recurrent FTS. A large-scale prospective study is warranted.


Subject(s)
Ambulatory Care Facilities , Child , Emergency Service, Hospital , Epilepsy , Humans , Ion Channels , Korea , Logistic Models , Magnesium , N-Methylaspartate , Prospective Studies , Seizures , Seizures, Febrile
18.
Article in English | WPRIM | ID: wpr-728626

ABSTRACT

3-(2-Carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, produces rapid antidepressant-like effects in animal models of depression. However, the molecular mechanisms underlying these behavioral actions remain unknown. Here, we demonstrate that CPP rapidly stimulates histone deacetylase (HDAC) 5 phosphorylation and nuclear export in rat hippocampal neurons. These effects are accompanied by calcium/calmodulin kinase II (CaMKII) and protein kinase D (PKD) phosphorylation. Behavioral experiments revealed that viral-mediated hippocampal knockdown of HDAC5 blocked the antidepressant effects of CPP in stressed animals. Taken together, our results imply that CPP acts via HDAC5 and suggest that HDAC5 is a common regulator contributing to the antidepressant actions of NMDA receptor antagonists such as CPP.


Subject(s)
Active Transport, Cell Nucleus , Animals , Depression , Hippocampus , Histone Deacetylases , Histones , Models, Animal , N-Methylaspartate , Neurons , Phosphorylation , Phosphotransferases , Protein Kinases , Rats
19.
Experimental Neurobiology ; : 539-549, 2018.
Article in English | WPRIM | ID: wpr-719050

ABSTRACT

Autism spectrum disorder (ASD) is a heterogeneous group of neurobehavioral disorders characterized by the two core domains of behavioral deficits, including sociability deficits and stereotyped repetitive behaviors. It is not clear whether the core symptoms of ASD are produced by dysfunction of the overall neural network of the brain or that of a limited brain region. Recent studies reported that excessive glutamatergic or dopaminergic inputs in the dorsal striatum induced sociability deficits and repetitive behaviors. These findings suggest that the dorsal striatum plays a crucial role in autistic-like behaviors. The present study addresses whether functional deficits of well-known ASD-related genes in the dorsal striatum also produce ASD core symptoms. This study also examines whether these behavioral changes can be modulated by rebalancing glutamate and/or dopamine receptor activity in the dorsal striatum. First, we found that the siRNA-mediated inhibition of Shank3, Nlgn3, Fmr1, Mecp2, or Tsc1 in the dorsal striatum produced mild to severe behavioral changes in sociability, cognition, and/or repetitive behaviors. The knockdown effects of Mecp2 and Tsc1 on behavioral changes were the most prominent. Next, we demonstrated that behavioral changes induced by striatal inhibition of MeCP2 and TSC1 were rescued by D-cycloserine (an NMDA agonist), fenobam (an mGluR5 antagonist), SCH23390 (a D1 antagonist), and/or ecopipam (a D1 partial antagonist), pharmacological drugs that are known to regulate ASD-like symptoms in animal models. Collectively, these results suggest that the dorsal striatum is a critical brain region that, when dysfunctional, produces the core symptoms of ASD.


Subject(s)
Autism Spectrum Disorder , Brain , Cognition , Glutamic Acid , Models, Animal , N-Methylaspartate , Receptors, Dopamine
20.
Rev. colomb. psiquiatr ; 46(4): 252-256, oct.-dic. 2017. graf
Article in Spanish | LILACS, COLNAL | ID: biblio-960147

ABSTRACT

Resumen Las encefalitis inmunitarias son un grupo particular de trastornos que se distinguen por su aproximación diagnostica única y manejo específico. Algunas de las manifestaciones iniciales son inespecíficas y difíciles de distinguir de encefalitis de otros orígenes, e incluso con los tests diagnósticos modernos aún hay cierto número de casos en que no se logra aclarar la causa específica. Entre ellas, las encefalitis anti-NMDAR son una particular forma de encefalitis inmunitaria que tiene manifestaciones clínicas distintivas, algunas de las cuales permiten al evaluador médico apuntar a un diagnóstico más preciso e iniciar tratamientos aun sin tener los reportes específicos de laboratorio. En este artículo se presentan 3 casos de pacientes pediátricos tratados como encefalitis anti-NMDAR, y después de comparar su presentación clínica, se revisa este trastorno específico y algunos de los datos más relevantes en su fisiopatología, como una forma de explicar las manifestaciones psiquiátricas iniciales, de cuyo reconocimiento inicial van a depender los apropiados diagnóstico y tratamiento.


Abstract Immune encephalitis is a diverse group of disorders that share some unique diagnostic approaches and specific treatments. Some of the initial manifestations are non-specific and difficult to distinguish from encephalitis of other aetiologies, and even with modern diagnostic tools there are still a number of cases for which definitive causes cannot be clarified. Among these, N-methyl-D-aspartate receptor (NMDAR) encephalitis is a particular form of immune encephalitis that has some distinctive clinical manifestations, which allows the clinical evaluator to suggest a more accurate diagnosis and start treatments even in the absence of specific laboratory tests. Three paediatric patients, who were treated for NMDAR encephalitis are described in this article, as well as comparing their clinical presentation. This specific disorder and some of the more relevant features of its physiopathology are reviewed in order to explain the initial psychiatric manifestations, for which early recognition is critical for an appropriate diagnosis and treatment.


Subject(s)
Humans , Male , Female , Child, Preschool , Child , Diagnosis , Anti-N-Methyl-D-Aspartate Receptor Encephalitis , Therapeutics , Causality , N-Methylaspartate , Encephalitis , Laboratories
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