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hippocampus model

Malik Nassan, Qingqin Li, Paul E Croarkin, Wenan Chen, Colin L Colby, Marin Veldic, Susan L McElroy, Gregory D Jenkins, Euijung Ryu, Julie M Cunningham, Marion Leboyer, Mark A Frye, Joanna M Biernacka
BACKGROUND: Although multiple genes have been implicated in bipolar disorder (BD), they explain only a small proportion of its heritability. Identifying additional BD risk variants may be impaired by phenotypic heterogeneity, which is usually not taken into account in genome-wide association studies (GWAS). BD with early age at onset is a more homogeneous familial form of the disorder associated with greater symptom severity. METHODS: We conducted a GWAS of early-onset BD (onset of mania/hypomania ≤19 years old) in a discovery sample of 419 cases and 1034 controls and a replication sample of 181 cases and 777 controls...
September 30, 2016: Journal of Affective Disorders
Laura de Diego-García, Mercedes Ramírez-Escudero, Álvaro Sebastián-Serrano, Juan Ignacio Diaz-Hernández, Jesús Pintor Just, José J Lucas, Miguel Díaz-Hernández
The Ubiquitin-Proteasome System (UPS) is essential for the regulation of the cellular proteostasis. Indeed, it has been postulated that an UPS dysregulation is the common mechanism that underlies several neurological disorders. Considering that extracellular nucleotides, through their selective P2Y2 receptor (P2Y2R), play a neuroprotective role in various neurological disorders that course with an UPS impairment, we wonder if this neuroprotective capacity resulted from their ability to modulate the UPS. Using a cellular model expressing two different UPS reporters, we found that the stimulation of P2Y2R by its selective agonist Up4U induced a significant reduction of UPS reporter levels...
October 18, 2016: Biochimica et Biophysica Acta
Paul R Territo, Jill A Meyer, Jonathan S Peters, Amanda A Riley, Brian P McCarthy, Mingzhang Gao, Min Wang, Mark A Green, Qi-Huang Zheng, Gary D Hutchins
BACKGROUND: The P2X7 receptor represents a novel molecular target for imaging neuroinflammation via PET. GSK1482160, a potent P2X7 receptor antagonist, has high receptor affinity, blood-brain barrier penetration, and has been recently radiolabel ((11)C-GSK1482160). Therefore, we report the initial physical and biological characterization of this novel ligand. METHODS: (11)C-GSK1482160 synthesis was according to published methods. Cell density studies were performed in human embryonic kidney cell lines expressing human P2X7 receptors (HEK293-hP2X7R) and analyzed by western blot analysis, immuno-fluorescence assay (IFA), and radiologic-immunohistochemistry (RIHC) using P2X7R polyclonal antibodies...
October 20, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Chao Dong, Ji-Chun Zhang, Wei Yao, Qian Ren, Min Ma, Chun Yang, Shigeyuki Chaki, Kenji Hashimoto
BACKGROUND: Similar to the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine, the metabotropic glutamate 2/3 (mGlu2/3) receptor antagonist, MGS0039 shows antidepressant effects. However, there are no reports comparing these two compounds in the social defeat stress model of depression. METHODS: We examined the effects of MGS0039 (1 mg/kg) and ketamine (10 mg/kg) on depression-like behavior in susceptible mice, after repeated social defeat stress. Protein levels of brain-derived neurotrophic factor (BDNF), TrkB, phospho-TrkB (p-TrkB), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (GluA1) and postsynaptic density protein 95 (PSD-95), and dendritic spine density in selected brain regions were measured...
October 7, 2016: International Journal of Neuropsychopharmacology
IbDanelo Cortez, Dmitry V Bulavin, Ping Wu, Erica L McGrath, Kathryn A Cunningham, Maki Wakamiya, John Papaconstantinou, Kelly T Dineley
A major aspect of mammalian aging is the decline in functional competence of many self-renewing cell types, including adult-born neuronal precursors. Since age-related senescence of self-renewal occurs simultaneously with chronic up-regulation of the p38MAPKalpha (p38α) signaling pathway, we used the dominant negative mouse model for attenuated p38α activity (DN-p38α(AF/+)) in which Thr180 and Tyr182 are mutated (T→A/Y→F) to prevent phosphorylation activation (DN-p38α(AF/+)) and kinase activity. As a result, aged DN-p38α(AF/+) mice are resistant to age-dependent decline in proliferation and regeneration of several peripheral tissue progenitors when compared to wild-type littermates...
October 17, 2016: Behavioural Brain Research
Hyeon-Joong Kim, Dae-Joong Kim, Eun-Ju Shin, Byung-Hwan Lee, Sun-Hye Choi, Sung-Hee Hwang, Hyewhon Rhim, Ik-Hyun Cho, Hyoung-Chun Kim, Seung-Yeol Nah
We previously showed that gintonin, an exogenous lysophosphatidic acid (LPA) receptor ligand, attenuated β-amyloid plaque formation in the cortex and hippocampus, and restored β-amyloid-induced memory dysfunction. Both endogenous LPA and LPA receptors play a key role in embryonic brain development. However, little is known about whether gintonin can induce hippocampal cell proliferation in adult wild-type mice and an APPswe/PSEN-1 double Tg mouse model of Alzheimer's disease (AD). In the present study, we examined the effects of gintonin on the proliferation of hippocampal neural progenitor cells (NPCs) in vitro and its effects on the hippocampal cell proliferation in wild-type mice and a transgenic AD mouse model...
October 17, 2016: Neurochemistry International
Min-Soo Kim, Ji Hye Bang, Jun Lee, Jung-Soo Han, Tae Gon Baik, Won Kyung Jeon
BACKGROUND: Ginkgo biloba extract (GBE)-a widely used nutraceutical-is reported to have diverse functions, including positive effects on memory and vasodilatory properties. Although numerous studies have assessed the neuroprotective properties of GBE in ischemia, only a few studies have investigated the neuro-pharmacological mechanisms of action of GBE in chronic cerebral hypoperfusion (CCH). PURPOSE: In the present study, we sought to determine the effects of GBE on CCH-induced neuroinflammation and cholinergic dysfunction in a rat model of bilateral common carotid artery occlusion (BCCAo)...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
X F Guo, Y N Zhao, J M Li, C X Chen, S X Li
Objective: To compare the changes in the expression of mTOR and beclin1 in the hippocampus of normal rats and intermittent hypoxia rats with cerebral ischemia/reperfusion, so as to explore the roles of mTOR/autophagy pathway in global cerebral ischemia/reperfusion injure aggravated by intermittent hypoxia. Methods: One hundred healthy male Wistar rats were randomly divided into: sham operation group(SO group, n=20), intermittent hypoxia group(IH group, n=20), merely ischemia/reperfusion group(I/R group, n=20), intermittent hypoxia ischemia/reperfusion group(IH+ I/R group, n=20), intermittent hypoxia ischemia/reperfusion+ mTOR inhibitor group(Inhibitor group, n=20)...
October 7, 2016: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke za Zhi, Chinese Journal of Otorhinolaryngology Head and Neck Surgery
Yimin Qiu, Dongmei Chen, Xiaojing Huang, Lina Huang, Liang Tang, Jihong Jiang, Lianhua Chen, Shitong Li
BACKGROUND: Limited surveys have assessed the performance of 5-hydroxytreptamine receptor 1A and its antagonist WAY-100635 in pharmacological manipulations targeting delirium therapies. The purpose of this paper was to assess the central pharmacological activity of WAY-100635 in a rat model of scopolamine-induced delirium and its underlying mechanism. RESULTS: A delirium rat model was established by intraperitoneal injection of scopolamine and behavioral changes evaluated through open field and elevated plus maze experiments...
October 19, 2016: BMC Neuroscience
Eider M Arenaza-Urquijo, Robin de Flores, Julie Gonneaud, Miranka Wirth, Valentin Ourry, William Callewaert, Brigitte Landeau, Stéphanie Egret, Florence Mézenge, Béatrice Desgranges, Gaël Chételat
Engagement in cognitive activity (CA) and physical activity (PA) during the lifespan may counteract brain atrophy later in life. Here, we investigated engagement in CA and PA during late adulthood in association with gray matter volume (GM) in normal older adults, with special focus on the hippocampus. Forty-five cognitively normal older individuals (mean age: 72) underwent T1-weighted MRI and self-reported CA and PA assessment. Whole brain voxel-wise multiple regression models were carried out to assess the relationships between CA, PA and GM volume adjusted by age and sex...
October 18, 2016: Brain Imaging and Behavior
Xiaolie He, Yanjing Zhu, Mei Wang, Guoxin Jing, Rongrong Zhu, Shilong Wang
Major depression is a complex neuropsychiatric disorder with few treatment approaches. The use of nontargeted antidepressants induced many side effects with their low efficacy. A more precise targeting strategy is to develop nanotechnology-based drug delivery systems; hence, we employed solid lipid nanoparticles (SLNs) to encapsulate HU-211 and curcumin (Cur). The antidepressant effects of the dual-drug nanoparticles (Cur/SLNs-HU-211) for major depression treatment were investigated in corticosterone-induced cellular and animal models of major depression...
2016: International Journal of Nanomedicine
Baomei Xia, Chang Chen, Hailou Zhang, Wenda Xue, Juanjuan Tang, Weiwei Tao, Ruyan Wu, Li Ren, Wei Wang, Gang Chen
Postpartum depression (PPD) affects over 10% of new mothers and adversely impacts the health of offspring. One of the greatest risk factors for PPD is prepregnancy stress but the underlying biological mechanism is unknown. Here we constructed an animal model which recapitulated prepregnancy stress induced PPD and tested the role of Akt-mTOR signaling in the hippocampus. Female virgin Balb/c mice received chronic restraint stress, followed by co-housing with a normal male mouse. We found that the chronic stress led to a transient depressive-like condition that disappeared within two weeks...
October 19, 2016: Scientific Reports
Henk-Jan Westeneng, Renée Walhout, Milou Straathof, Ruben Schmidt, Jeroen Hendrikse, Jan H Veldink, Martijn P van den Heuvel, Leonard H van den Berg
BACKGROUND: In patients with a C9orf72 repeat expansion (C9+), a neuroimaging phenotype with widespread structural cerebral changes has been found. We aimed to investigate the specificity of this neuroimaging phenotype in patients with amyotrophic lateral sclerosis (ALS). METHODS: 156 C9- and 14 C9+ patients with ALS underwent high-resolution T1-weighted MRI; a subset (n=126) underwent diffusion-weighted imaging. Cortical thickness, subcortical volumes and white matter integrity were compared between C9+ and C9- patients...
October 18, 2016: Journal of Neurology, Neurosurgery, and Psychiatry
Xuemei Lei, Chuansheng Chen, Chunhui Chen, Qinghua He, Robert K Moyzis, Gui Xue, Qi Dong
Cooperativeness is an essential behavioral trait evolved to facilitate group living. Social and cognitive mechanisms involved in cooperation (e.g., motivation, reward encoding, action evaluation, and executive functions) are sub-served by the striatal-projected circuits, whose physical existence has been confirmed by animal studies, human postmortem studies, and in vivo human brain studies. The current study investigated the associations between Cooperativeness and fiber connectivities from the striatum to nine subcortical and cortical regions, including the amygdala, hippocampus, medial orbitofrontal cortex, lateral orbitofrontal cortex, ventrolateral prefrontal cortex, dorsolateral prefrontal cortex, posterior cingulate cortex/retrosplenial cortex, dorsal cingulate cortex, and rostral cingulate cortex...
2016: PloS One
Claudia Balducci, Angelisa Frasca, Margherita Zotti, Pietro La Vitola, Emanuela Mhillaj, Emanuele Grigoli, Martina Iacobellis, Federica Grandi, Massimo Messa, Laura Colombo, Monica Molteni, Luigia Trabace, Carlo Rossetti, Mario Salmona, Gianluigi Forloni
[Background] Amyloid-β oligomers (AβO) are species mainly involved in the synaptic and cognitive dysfunction in Alzheimer's disease. Although their action has been described mainly at neuronal level, it is now clear that glial cells govern synaptic activity in their resting state, contributing to new learning and memory establishment. In contrast, when activated, they may lead to synaptic and cognitive dysfunction. Using a reliable acute AβO-mediated mouse model of AD, we explored whether the memory alteration AβOs induce relies on the activation of glial cells, and if Toll-like receptor 4 (TLR4), pivotal in the initiation of an immune response, is involved...
October 14, 2016: Brain, Behavior, and Immunity
Eunchai Kang, Daniel A Berg, Orion Furmanski, William M Jackson, Yun Kyoung Ryu, Christy D Gray, C David Mintz
The mechanism by which anesthetics might act on the developing brain in order to cause long term deficits remains incompletely understood. The hippocampus has been identified as a structure that is likely to be involved, as rodent models show numerous deficits in behavioral tasks of learning that are hippocampal-dependent. The hippocampus is an unusual structure in that it is the site of large amounts of neurogenesis postnatally, particularly in the first year of life in humans, and these newly generated neurons are critical to the function of this structure...
October 14, 2016: Neurotoxicology and Teratology
Joshua J Emrick, Brooks A Gross, Brett T Riley, Gina R Poe
STUDY OBJECTIVES: Investigators assign sleep-waking states using brain activity collected from a single site, assuming that states occur at the same time throughout the brain. We sought to determine if sleep-waking states differ between two separate structures: the hippocampus and neocortex. METHODS: We measured electrical signals (electroencephalograms and electromyograms) during sleep from the hippocampus and neocortex of five freely behaving adult male rats. We assigned sleep-waking states in 10-sec epochs based on standard scoring criteria across a 4 h recording and analyzed and compared states and signals from simultaneous epochs between sites...
October 10, 2016: Sleep
D K Rieger, E Navarro, I Buendia, E Parada, L González-Lafuente, R Leon, A P Costa, I A Heinrich, K S Nascimento, B S Cavada, M G Lopez, J Egea, R B Leal
Lectins are proteins that bind cellular glycans and can modulate various neuronal functions. We have evaluated the neuroprotective effect of ConBr, a lectin purified from the seeds of Canavalia brasiliensis in a model of rat organotypic hippocampal cultures (OHCs) exposed to oxygen and glucose deprivation (OGD). OGD for 15 min followed by 24 h re-oxygenation significantly increased cell death, caused mitochondrial depolarization and increased reactive oxygen species (ROS) in CA1 region of OHCs. ConBr (0.1 μg/mL) added during the re-oxygenation period counteracted cell death, mitochondrial depolarization and overproduction of ROS induced by OGD...
October 17, 2016: Neurochemical Research
Suman Pradhan, Christine Pellino, Kayleigh MacMaster, Dennis Coyle, Alison A Weiss
Seizures and neurologic involvement have been reported in patients infected with Shiga toxin (Stx) producing E. coli, and hemolytic uremic syndrome (HUS) with neurologic involvement is associated with more severe outcome. We investigated the extent of renal and neurologic damage in mice following injection of the highly potent form of Stx, Stx2a, and less potent Stx1. As observed in previous studies, Stx2a brought about moderate to acute tubular necrosis of proximal and distal tubules in the kidneys. Brain sections stained with hematoxylin and eosin (H&E) appeared normal, although some red blood cell congestion was observed...
2016: Frontiers in Cellular and Infection Microbiology
Miranda C Staples, Chitra D Mandyam
Alcohol use disorder currently affects approximately 18 million Americans, with at least half of these individuals having significant cognitive impairments subsequent to their chronic alcohol use. This is most widely apparent as frontal cortex-dependent cognitive dysfunction, where executive function and decision-making are severely compromised, as well as hippocampus-dependent cognitive dysfunction, where contextual and temporal reasoning are negatively impacted. This review discusses the relevant clinical literature to support the theory that cognitive recovery in tasks dependent on the prefrontal cortex and hippocampus is temporally different across extended periods of abstinence from alcohol...
2016: Frontiers in Psychiatry
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