Dongqing Xia, Cuiting Min, Yinhua Chen, Ru Ling, Mengying Chen, Xiaonan Li
Preterm infants in neonatal intensive care units are inevitably subjected to numerous painful procedures. However, little is known about the consequences of early pain experience on fear memory formation later in life. We hypothesized that exposure to repetitive pain in early life triggered hippocampal synaptic plasticity and resulted in memory deficiency in prepubertal and adult rats. From the day of birth (P0) to postnatal day 7 (P7), neonatal male rat pups were randomly assigned to either needle pricks or tactile touches repetitively every 6 h...
2020: Frontiers in Neuroscience
Shakiba Nasiri Boroujeni, Zahra Lorigooini, Fatemeh Rahimi Boldaji, Hossein Amini-Khoei
BACKGROUND AND AIM: Anxiety is one of the most common psychiatric disorders that lead to disruption of daily and quality of life. Routine medications have many side effects and cause physical dependence and psychosocial addiction. Diosgenin is a phytosteroid found in a number of herbs. The aim of present study was to investigate the anxiolytic-like effect of diosgenin in the maternal separation model in male mice focusing on the role of NMDA receptors. MATERIAL AND METHODS: Maternal separation (MS) paradigm was performed daily (3 h) from postnatal day (PND) 2-14...
July 16, 2020: Current Pharmaceutical Design
Fawaz Alasmari, Hasan Alhaddad, Woonyen Wong, Richard L Bell, Youssef Sari
Exposure to ethanol commonly manifests neuroinflammation. Beta (β)-lactam antibiotics attenuate ethanol drinking through upregulation of astroglial glutamate transporters, especially glutamate transporter-1 (GLT-1), in the mesocorticolimbic brain regions, including the nucleus accumbens (Acb). However, the effect of β-lactam antibiotics on neuroinflammation in animals chronically exposed to ethanol has not been fully investigated. In this study, we evaluated the effects of ampicillin/sulbactam (AMP/SUL, 100 and 200 mg/kg, i...
July 10, 2020: Biomolecules
Ying Chun Li, Xing Xing Zheng, Si Zhe Xia, Yang Li, Huan Huan Deng, Xing Wang, Yi Wei Chen, Yi Song Yue, Jiao He, Yan Jun Cao
BACKGROUND: Prenatal stress (PS) can increase the risk of nervous, endocrine and metabolic diseases and induce depression in offspring. Paeoniflorin (PA) is an amorphous glucoside isolated from the aqueous extract of roots of the peony plant (Paeonia lactiflora Pall.) and exerts various pharmacological effects in the nervous system. METHODS: Male prenatally stressed offspring were used to investigate the antidepression-like effects and possible mechanism of PA. We measured animal behavior, HPA axis, Nissil staining, and Ng expression...
September 1, 2020: Journal of Affective Disorders
Felipe Alberto Gómez Ávila, Maricarmen Fernández González-Aragón, Álvaro Moreno Avellán, Daniel San-Juan
PURPOSE: Anti-N-methyl-D-aspartate receptor encephalitis is produced by an autoimmune reaction against macromolecular structures that form ionotropic receptors for glutamic acid NR2A and NR2B subunits. Other important findings are the multiple clinical and paraclinical manifestations, among which the EEG stands out. We characterized EEG patterns and their association with functional disability and hospitalization time in patients with anti-N-methyl-D-aspartate receptor encephalitis admitted in our center...
July 1, 2020: Journal of Clinical Neurophysiology: Official Publication of the American Electroencephalographic Society
Haiyang Yu, Lin Ma, Di Liu, Yu Wang, Xiucong Pei, Zhiwen Duan, Mingyue Ma, Yumin Zhang
Bisphenol A (BPA), can lead to learning and memory impairment, but the underlying mechanism is poorly understood. Researchers have indicated that the N-methyl-D-aspartate receptor (NMDAR)/postsynaptic density protein 95 (PSD-95)/neuronal nitric oxide synthase (nNOS)-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway greatly contributes to learning and memory process. Pregnant rats were exposed to 0, 0.05, 0.5, 5 and 50 mg/kg/day BPA via oral gavage from gestational day (GD) 5 to GD 19. Morris water maze, transmission electron microscope, western blot, real time PCR, biochemical analysis and ELISA were used to analyze the changes in behavior, synaptic ultrastructure, protein and gene expression of NMDAR, PSD-95, nNOS, together with nNOS activity, NO (Nitrate reductase method) and cGMP levels of the rat pups at different growth stages...
June 29, 2020: Environmental Pollution
Adel A Gomaa, Rania M Makboul, Mohamed A El-Mokhtar, Engy A Abdel-Rahman, Israa A Ahmed, Mariam A Nicola
Recent studies raise the possibility that donepezil can delay the progression of Alzheimer's disease (AD). This research evaluated the efficacy of donepezil in an animal model with brain insulin resistance and AD-like alterations. Rats were fed with high-fat/high-fructose (HF/Hfr) diet during the study period (17 weeks) and received one injection of streptozotocin (STZ) (25mg/kg) after 8 weeks of starting the study. Diabetic (T2D) rats were treated with donepezil (4 mg/kg; p.o.) or vehicle for 8 weeks after STZ injection...
June 30, 2020: Fundamental & Clinical Pharmacology
Maryam Anjomshoa, Shakiba Nasiri Boroujeni, Sorayya Ghasemi, Zahra Lorigooini, Ahmad Amiri, Shima Balali-Dehkordi, Hossein Amini-Khoei
Methods: Mouse neonates were exposed to MS paradigm 3 hours daily from postnatal days (PND) 2 to 14. The control and MS mice were divided separately into 16 groups ( n = 8) (8 groups for each set) including mice that received normal saline, mice that received rutin at doses of 10, 50, and 100 mg/kg, mice that received NMDA at a dose of 150 mg/kg, mice that received ketamine (NMDA antagonist) at a dose of 0.25 mg/kg, mice that received NMDA antagonist plus a subeffective dose of rutin, and mice that received NMDA plus an effective dose of rutin...
2020: Behavioural Neurology
Ji-Eun Kim, Duk-Shin Lee, Tae-Hyun Kim, Hana Park, Min-Ju Kim, Tae-Cheon Kang
In the brain, murine double minute-2 (Mdm2), an E3-ubiquitin ligase, modulates neuronal excitability by regulating glutamate receptor and postsynaptic density 95 (PSD95) levels through ubiquitination. Thus, Mdm2 is relevant to epileptic seizures in human patients. Although phosphorylation at serine (S) 166 site by AKT increases Mdm2 activity, phosphatases of Mdm2 have been still elusive. Here, we demonstrate the novel function of pyridoxal-5'-phosphate phosphatase/chronophin (PLPP/CIN) in Mdm2 dephosphorylation that may negatively regulate PSD95 ubiquitination...
June 16, 2020: Experimental Neurology
Mia Levite, Daniel Zelig, Alon Friedman, Nili Ilouz, Raya Eilam, Zohar Bromberg, Ally Ahmed Ramadhan Lasu, Sagit Arbel-Alon, Shimon Edvardson, Mark Tarshish, Lul P Riek, Richard Lino Lako, Benjamin Reubinoff, Mario Lebendiker, Dayana Yaish, Alexandra Stavsky, Eithan Galun
Nodding Syndrome (NS) is a fatal pediatric epilepsy of unknown etiology, accompanied by multiple neurological impairments, and associated with Onchocerca volvulus (Ov), malnutrition, war-induced trauma, and other insults. NS patients have neuroinflammation, and ~50% have cross-reactive Ov/Leiomodin-1 neurotoxic autoimmune antibodies. RESULTS: Studying 30 South Sudanese NS patients and a similar number of healthy subjects from the same geographical region, revealed autoimmune antibodies to 3 extracellular peptides of ionotropic glutamate receptors in NS patients: AMPA-GluR3B peptide antibodies (86%), NMDA-NR1 peptide antibodies (77%) and NMDA-NR2 peptide antibodies (87%) (in either 1:10, 1:100 or 1:1000 serum dilution)...
April 10, 2020: Journal of Autoimmunity
Chan-Min Liu, Zhi-Kai Tian, Yu-Jia Zhang, Qing-Lei Ming, Jie-Qiong Ma, Li-Ping Ji
Gastrodin (GAS), the main phenolic glycoside extracted from Gastrodia elata Blume, exhibited potential neuroprotective properties. Here we examined the protective effects of GAS against lead(Pb)-induced nerve injury in mice, and explores its underlying mechanisms. Our research findings revealed that GAS improved behavioral deficits in Pb-exposed mice. GAS reduced the accumulation of p-tau and amyloid-beta (Aβ). GAS inhibited Pb-induced inflammation in the brain, as indicated by the decreased levels of pro-inflammatory cytokines, including tumor necrosis factor-a (TNF-α), cyclooxygenase-2 (COX-2)...
June 17, 2020: Nutrients
Laura Schnöder, Gilles Gasparoni, Karl Nordström, Andrea Schottek, Inge Tomic, Anne Christmann, Karl H Schäfer, Michael D Menger, Jörn Walter, Klaus Fassbender, Yang Liu
Alzheimer's disease (AD) is the leading cause of dementia with very limited therapeutic options. Amyloid β (Aβ) and phosphorylated Tau (p-Tau) are key pathogenic molecules in AD. P38α-MAPK is specifically activated in AD lesion sites. However, its effects on AD pathogenesis, especially on p-Tau-associated brain pathology, and the underlying molecular mechanisms remain unclear. We mated human APP-transgenic mice and human P301S Tau-transgenic mice with mapk14-floxed and neuron-specific Cre-knock-in mice. We observed that deletion of p38α-MAPK specifically in neurons improves the cognitive function of both 9-month-old APP and Tau-transgenic AD mice, which is associated with decreased Aβ and p-Tau load in the brain...
May 31, 2020: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Gang Lei, Fei Liu, Peng Liu, Tong Jiao, Liu Yang, Zheng Chu, Li-Sha Deng, Yan Li, Yong-Hui Dang
The histidine triad nucleotide binding protein 1 (HINT1) is closely related to many neuropsychiatric disorders. Clinical studies supported that mutations in the Hint1 gene correlated potentially with schizophrenia. In addition, Hint1 gene knockout (KO) mice exhibited hyperactivity induced by amphetamine and apomorphine. However, it is still unclear whether this animal model exhibits schizophrenia-like behaviors and, if so, their underlying mechanisms remain to be elucidated. Thus, our study sought to evaluate schizophrenia-like behaviors in Hint1-KO mice, and explore the associated changes in neuronal structural plasticity and schizophrenia-related molecules...
May 18, 2020: Schizophrenia Research
Yu Liu, Guang-Jing Zou, Bo-Xuan Tu, Zhao-Lan Hu, Cong Luo, Yan-Hui Cui, Yang Xu, Fang Li, Ru-Ping Dai, Fang-Fang Bi, Chang-Qi Li
Major depression disorder is one of the most common psychiatric disorders that greatly threaten the mental health of a large population worldwide. Previous studies have shown that endoplasmic reticulum (ER) stress plays an important role in the pathophysiology of depression, and current research suggests that brain-derived neurotrophic factor precursor (proBDNF) is involved in the development of depression. However, the relationship between ER and proBDNF in the pathophysiology of depression is not well elucidated...
May 6, 2020: Neurotoxicity Research
Ying Cai, Baoshan Qiu, Mengshi Liao, Xiaolu Liu, Jing Lin, Linfang Lan, Guangqing Xu, Yuhua Fan
We investigated whether intermittent theta burst stimulation (iTBS) can improve the spatial cognitive function of rats with hypertension-induced cerebral small vessel disease. To prove our hypothesis, stroke-prone renovascular hypertensive rats (RHRSPs) were treated with iTBS beginning at postoperative week 22. The Morris water maze was performed to assess spatial cognitive function. The expression of the N-methyl-d-aspartate receptor (NMDAR) subunits NR1, NR2A and NR2B, calcium/calmodulin-dependent protein kinase IIα (CaMKIIα), p-CaMKIIα and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit 1 (GluR1) in the hippocampus were evaluated by western blot analysis...
June 15, 2020: Neuroscience
Daniel T Baptista-Hon, Mark Smith, Samuel Singleton, Lysbeth H Antonides, Niamh Nic Daeid, Craig McKenzie, Tim G Hales
BACKGROUND AND PURPOSE: A fluorinated derivative (2F-MT-45) of the synthetic μ-opioid receptor agonist MT-45 (1-cyclohexyl-4-(1,2-diphenylethyl)piperazine), was recently identified in a seized illicit tablet. While MT-45 is a Class A drug, banned in a number of countries, nothing is known about the pharmacology of 2F-MT-45. This study compares the pharmacology of MT-45, its fluorinated derivatives and two of its metabolites. EXPERIMENTAL APPROACH: We used a β-arrestin2 recruitment assay in CHO cells stably expressing μ receptors to quantify the apparent potencies and efficacies of known (MT-45, morphine, fentanyl and DAMGO) and potential agonists...
April 4, 2020: British Journal of Pharmacology
Duk-Shin Lee, Ji-Eun Kim
Postsynaptic density-95 (PSD95), a major scaffolding protein, is critical in coupling N-methyl-D-aspartate receptor (NMDAR) to cellular signaling networks in the central nervous system. A couple of cysteine residues in the N-terminus of PSD95 are potential sites for disulfide bonding, S -nitrosylation and/or palmitoylation. Protein disulfide isomerase (PDI) reduces disulfide bonds (S-S) to free thiol (-SH) on various proteins. However, the involvement of PDI in disulfide bond formation/ S -nitrosylation of PSD95 and its role in epilepsy are still unknown...
March 18, 2020: International Journal of Molecular Sciences
Daniela Silva-Adaya, Lucio Antonio Ramos-Chávez, Pavel Petrosyan, Wendy Leslie González-Alfonso, Alegna Pérez-Acosta, Maria E Gonsebatt
Exposure to toxic metals and metalloids is an important cause of preventable diseases worldwide. Inorganic arsenic (iAs) affects several organs and tissues, causing neurobehavioral alterations in the central nervous system (CNS) that might lead to neurodegeneration. In this work, we wanted to explore the time- and dose-related changes on glutathione (GSH) levels in several regions of the CNS, such as the cortex, striatum, hippocampus, and cerebellum, to identify the initial cellular changes associated to GSH depletion due to iAs exposure...
2020: Frontiers in Cellular Neuroscience
Machi Kuroda, Takashi Matsuwaki, Yoshinori Tanaka, Keitaro Yamanouchi, Masugi Nishihara
Progranulin (PGRN) is a glycoprotein that is widely expressed among organs, including the central nervous system. PGRN insufficiency is involved in various neurodegenerative disorders such as frontotemporal dementia, Alzheimer's disease, and neuronal ceroid lipofuscinosis. One of the major causes of neuronal damage is hyperactivation of the cerebrum triggered by upregulation of excitatory systems. In the present study, we examined the possible involvement of PGRN in modulating excitability of the cerebrum using wild type and PGRN-deficient mice...
March 12, 2020: Neuroreport
Shuisheng Lei, Yan He, Ziting Zhu, Zhongrui Liu, Yuwan Lin, Yuehua He, Sheng Du, Xiang Chen, Pingyi Xu, Xiaoqin Zhu
Aquaporin 4 (AQP4), a water-specific channel protein locating on the astrocyte membrane, has been found to be antagonist, agonist and undergone closely related to epilepsy. Our previous study showed that inhibition of an N-methyl-D-aspartate receptor (NMDAR) subunit NR2A can suppress epileptic seizures, suggesting that AQP4 is potentially involved in NR2A-mediated epilepsy treatment. In this study, we aimed to explore the relevance of AQP4 in NR2A-mediated seizures treatment in pentylenetetrazol (PTZ)-induced rat models...
February 27, 2020: Cellular and Molecular Neurobiology
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