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https://www.readbyqxmd.com/read/27900211/in-vivo-expression-of-reprogramming-factors-increases-hippocampal-neurogenesis-and-synaptic-plasticity-in-chronic-hypoxic-ischemic-brain-injury
#1
Soohyun Wi, Ji Hea Yu, MinGi Kim, Sung-Rae Cho
Neurogenesis and synaptic plasticity can be stimulated in vivo in the brain. In this study, we hypothesized that in vivo expression of reprogramming factors such as Klf4, Sox2, Oct4, and c-Myc would facilitate endogenous neurogenesis and functional recovery. CD-1® mice were induced at 1 week of age by unilaterally carotid artery ligation and exposure to hypoxia. At 6 weeks of age, mice were injected GFP only or both four reprogramming factors and GFP into lateral ventricle. Passive avoidance task and open field test were performed to evaluate neurobehavioral function...
2016: Neural Plasticity
https://www.readbyqxmd.com/read/27894930/sex-dependent-influence-of-chronic-mild-stress-cms-on-voluntary-alcohol-consumption-study-of-neurobiological-consequences
#2
Eva M Marco, Javier Antonio Ballesta, Carlos Irala, María-Donina Hernández, María Elisa Serrano, Virginia Mela, Meritxell López-Gallardo, María-Paz Viveros
Alcohol use disorder and depression are highly comorbid, and both conditions exhibit important sexual dimorphisms. Here, we aimed to investigate voluntary alcohol consumption after 6weeks of chronic mild stress (CMS) in Wistar rats - employed as an animal model of depression. Male and female rats were investigated, and changes in several molecular markers were analysed in frontal cortex (FCx) and hippocampal formation (HF). CMS induced depressive-like responses in the forced swimming test - increased immobility time - in male and female animals, without affecting anhedonia (sucrose preference test) nor motor activity (holeboard); body weight gain and food intake were diminished only among CMS males...
November 25, 2016: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/27878552/strength-and-aerobic-exercises-improve-spatial-memory-in-aging-rats-through-stimulating-distinct-neuroplasticity-mechanisms
#3
Thais Ceresér Vilela, Alexandre Pastoris Muller, Adriani Paganini Damiani, Tamires Pavei Macan, Sabrina da Silva, Paula Bortoluzzi Canteiro, Alisson de Sena Casagrande, Giulia Dos Santos Pedroso, Renata Tiscoski Nesi, Vanessa Moraes de Andrade, Ricardo Aurino de Pinho
Aging is associated with impaired cognition and memory and increased susceptibility to neurodegenerative disorders. Physical exercise is neuroprotective; however, the major evidence of this effect involves studies of only aerobic training in young animals. The benefits of other exercise protocols such as strength training in aged animals remains unknown. Here, we investigated the effect of aerobic and strength training on spatial memory and hippocampal plasticity in aging rats. Aging Wistar rats performed aerobic or strength training for 50 min 3 to 4 days/week for 8 weeks...
November 22, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27867342/the-family-of-crumbs-genes-and-human-disease
#4
REVIEW
Anne M Slavotinek
The family of vertebrate Crumbs proteins, homologous to Drosophila Crumbs (Crb), share large extracellular domains with epidermal growth factor-like repeats and laminin-globular domains, a single transmembrane domain, and a short intracellular C-terminus containing a single membrane proximal 4.1/ezrin/radixin/moesin-binding domain and PSD-95/Discs large/ZO-1-binding motifs. There are 3 Crb genes in humans - Crumbs homolog-1 (CRB1), Crumbs homolog-2 (CRB2), and Crumbs homolog-3 (CRB3). Bilallelic loss-of-function mutations in CRB1 cause visual impairment, with Leber's congenital amaurosis and retinitis pigmentosa, whereas CRB2 mutations are associated with raised maternal serum and amniotic fluid alpha feto-protein levels, ventriculomegaly/hydrocephalus, and renal disease, ranging from focal segmental glomerulosclerosis to congenital Finnish nephrosis...
October 2016: Molecular Syndromology
https://www.readbyqxmd.com/read/27861918/maguk-dynamics-reveal-regional-and-developmental-specificity-of-synapse-stability
#5
Jonathan M Levy, Roger A Nicoll
Fast excitatory transmission in the brain requires localization of glutamate receptors to synapses. The MAGUK family of synaptic scaffolding proteins is critical for localization of glutamate receptors to synapses. Although the MAGUKs are well-studied in reduced preparations and young animals, little data exists on their role in adult animals. Here, we present a detailed developmental study of the role of the MAGUKs during rat development. We first confirm by knockdown experiments that MAGUKs are essential for glutamatergic transmission in young animals and cultured slices, and increases in PSD-95 by overexpression causes correlated increases in glutamatergic transmission...
November 8, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27859797/in-vitro-and-in-vivo-effects-of-a-novel-dimeric-inhibitor-of-psd-95-on-excitotoxicity-and-functional-recovery-after-experimental-traumatic-brain-injury
#6
Jens Bak Sommer, Anders Bach, Hana Malá, Kristian Strømgaard, Jesper Mogensen, Darryl Scott Pickering
PSD-95 inhibitors have been shown to be neuroprotective in stroke, but have only to a very limited extent been evaluated in the treatment of traumatic brain injury (TBI) that has pathophysiological mechanisms in common with stroke. The aims of the current study were to assess the effects of a novel dimeric inhibitor of PSD-95, UCCB01-147, on histopathology and long-term cognitive outcome after controlled cortical impact (CCI) in rats. As excitotoxic cell death is thought to be a prominent part of the pathophysiology of TBI, we also investigated the neuroprotective effects of UCCB01-147 and related compounds on NMDA-induced cell death in cultured cortical neurons...
November 17, 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27836791/pharmacological-inhibition-of-pten-attenuates-cognitive-deficits-caused-by-neonatal-repeated-exposures-to-isoflurane-via-inhibition-of-nr2b-mediated-tau-phosphorylation-in-rats
#7
Lei Tan, Xin Chen, Wei Wang, Jianfang Zhang, Shiyong Li, Yilin Zhao, Jintao Wang, Ailin Luo
Evidence has shown that children exposed to repeated anesthesia in early childhood display long-term cognitive disabilities. However, the underlying mechanisms remain largely unclear. Our previous study has indicated the involvement of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in isoflurane-induced decrease of self-renewal capacity in hippocampal neural precursor cells. Additionally, it is demonstrated by others that PTEN inhibition could protect against cognitive impairment via reduction of tau phosphorylation in the alzheimer's disease model...
November 8, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27833158/the-role-of-posttraumatic-hypothermia-in-preventing-dendrite-degeneration-and-spine-loss-after-severe-traumatic-brain-injury
#8
Chuan-Fang Wang, Cheng-Cheng Zhao, Gan Jiang, Xiao Gu, Jun-Feng Feng, Ji-Yao Jiang
Posttraumatic hypothermia prevents cell death and promotes functional outcomes after traumatic brain injury (TBI). However, little is known regarding the effect of hypothermia on dendrite degeneration and spine loss after severe TBI. In the present study, we used thy1-GFP transgenic mice to investigate the effect of hypothermia on the dendrites and spines in layer V/VI of the ipsilateral cortex after severe TBI. We found that hypothermia (33 °C) dramatically prevented dendrite degeneration and spine loss 1 and 7 days after CCI...
November 11, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27832448/developmental-exposure-to-cocaine-dynamically-dysregulates-cortical-arc-arg3-1-modulation-in-response-to-a-challenge
#9
Lucia Caffino, Giuseppe Giannotti, Francesca Mottarlini, Giorgio Racagni, Fabio Fumagalli
During adolescence, the medial prefrontal cortex (mPFC) is still developing. We have previously shown that developmental cocaine exposure alters mPFC's ability to cope with challenging events. In this manuscript, we exposed rats developmentally treated with cocaine to a novelty task and analyzed the molecular changes of mPFC. Rats were exposed to cocaine from post-natal day (PND) 28 to PND 42 and sacrificed at PND 43, immediately after the novel object recognition (NOR) test. Cocaine-treated rats spent more time exploring the novel object than saline-treated counterparts, suggesting an increased response to novelty...
November 10, 2016: Neurotoxicity Research
https://www.readbyqxmd.com/read/27810933/nmdars-adapt-to-neurotoxic-hiv-protein-tat-downstream-of-a-glun2a-ubiquitin-ligase-signaling-pathway
#10
Matthew V Green, Stanley A Thayer
: HIV-associated neurocognitive disorder (HAND) affects about half of HIV-infected patients. Infected non-neuronal cells release neurotoxic factors such as the viral protein, transactivator of transcription (Tat), that potentiate NMDAR function. NMDARs regulate synaptic changes observed following exposure to HIV proteins, which may underlie cognitive impairment in HAND patients. Here we used patch-clamp recording to measure NMDAR-mediated currents in rat hippocampal cultures following exposure to Tat...
November 3, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27800545/loss-of-syndig1-reduces-excitatory-synapse-maturation-but-not-formation-in-vivo
#11
George Chenaux, Lucas Matt, Travis C Hill, Inderpreet Kaur, Xiao-Bo Liu, Lyndsey M Kirk, David J Speca, Samuel A McMahon, Karen Zito, Johannes W Hell, Elva Díaz
Modification of the strength of excitatory synaptic connections is a fundamental mechanism by which neural circuits are refined during development and learning. Synapse Differentiation Induced Gene 1 (SynDIG1) has been shown to play a key role in regulating synaptic strength in vitro. Here, we investigated the role of SynDIG1 in vivo in mice with a disruption of the SynDIG1 gene rather than use an alternate loxP-flanked conditional mutant that we find retains a partial protein product. The gene-trap insertion with a reporter cassette mutant mice shows that the SynDIG1 promoter is active during embryogenesis in the retina with some activity in the brain, and postnatally in the mouse hippocampus, cortex, hindbrain, and spinal cord...
September 2016: ENeuro
https://www.readbyqxmd.com/read/27798707/a-single-postnatal-dose-of-dexamethasone-enhances-memory-of-rat-pups-later-in-life
#12
Kuen-Jer Tsai, Chun-I Sze, Yung-Chieh Lin, Yuh-Jyh Lin, Ting-Hui Hsieh, Chyi-Her Lin
Postnatal dexamethasone (Dex) therapy is associated with adverse neurodevelopmental outcomes, which might be related to its timing of administration. We used time-dated pregnant Wistar albino rats, whose litters were divided into experimental (Dex) and control groups intraperitoneally administered one dose of Dex (0.5 mg/kg) or normal saline (NS), respectively, at either day 1 (P1) or 7 (P7). The magnitude of the contextual freezing response and performance on the Morris water maze were significantly higher in the Dex-P7 group than in those of the other groups at P56...
2016: PloS One
https://www.readbyqxmd.com/read/27798183/%C3%AE-2%C3%AE-2-controls-the-function-and-trans-synaptic-coupling-of-cav1-3-channels-in-mouse-inner-hair-cells-and-is-essential-for-normal-hearing
#13
Barbara Fell, Stephanie Eckrich, Kerstin Blum, Tobias Eckrich, Dietmar Hecker, Gerald J Obermair, Stefan Münkner, Veit Flockerzi, Bernhard Schick, Jutta Engel
: The auxiliary subunit α2δ2 modulates the abundance and function of voltage-gated calcium channels. Here we show that α2δ2 mRNA is expressed in neonatal and mature hair cells. A functional α2δ2-null mouse, the ducky mouse (du), showed elevated auditory brainstem response click and frequency-dependent hearing thresholds. Otoacoustic emissions were not impaired pointing to normal outer hair cell function. Peak Ca(2+) and Ba(2+) currents of mature du/du inner hair cells (IHCs) were reduced by 30-40%, respectively, and gating properties, such as the voltage of half-maximum activation and voltage sensitivity, were altered, indicating that Cav1...
October 26, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27784858/reproductive-experience-modified-dendritic-spines-on-cortical-pyramidal-neurons-to-enhance-sensory-perception-and-spatial-learning-in-rats
#14
Jeng-Rung Chen, Seh Hong Lim, Sin-Cun Chung, Yee-Fun Lee, Yueh-Jan Wang, Guo-Fang Tseng, Tsyr-Jiuan Wan
Behavioral adaptations during motherhood are aimed at increasing reproductive success. Alterations of hormones during motherhood could trigger brain morphological changes to underlie behavioral alterations. Here we investigated whether motherhood changes a rat's sensory perception and spatial memory in conjunction with cortical neuronal structural changes. Female rats of different statuses, including virgin, pregnant, lactating, and primiparous rats were studied. Behavioral test showed that the lactating rats were most sensitive to heat, while rats with motherhood and reproduction experience outperformed virgin rats in a water maze task...
October 25, 2016: Experimental Animals
https://www.readbyqxmd.com/read/27765808/rapid-and-sustained-antidepressant-action-of-the-mglu2-3-receptor-antagonist-mgs0039-in-the-social-defeat-stress-model-comparison-with-ketamine
#15
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 receptor antagonist ketamine, the metabotropic glutamate 2/3 receptor antagonist, MGS0039, shows antidepressant effects. However, there are no reports comparing these 2 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, TrkB, phospho-TrkB, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (GluA1), postsynaptic density protein 95, and dendritic spine density in selected brain regions were measured...
October 27, 2016: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27756895/mpp2-is-a-postsynaptic-maguk-scaffold-protein-that-links-syncam1-cell-adhesion-molecules-to-core-components-of-the-postsynaptic-density
#16
Nils Rademacher, Bettina Schmerl, Jennifer A Lardong, Markus C Wahl, Sarah A Shoichet
At neuronal synapses, multiprotein complexes of trans-synaptic adhesion molecules, scaffold proteins and neurotransmitter receptors assemble to essential building blocks required for synapse formation and maintenance. Here we describe a novel role for the membrane-associated guanylate kinase (MAGUK) protein MPP2 (MAGUK p55 subfamily member 2) at synapses of rat central neurons. Through interactions mediated by its C-terminal SH3-GK domain module, MPP2 binds to the abundant postsynaptic scaffold proteins PSD-95 and GKAP and localises to postsynaptic sites in hippocampal neurons...
October 19, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27743829/acute-agmatine-administration-similar-to-ketamine-reverses-depressive-like-behavior-induced-by-chronic-unpredictable-stress-in-mice
#17
Vivian B Neis, Luis E B Bettio, Morgana Moretti, Priscila B Rosa, Camille M Ribeiro, Andiara E Freitas, Filipe M Gonçalves, Rodrigo B Leal, Ana Lúcia S Rodrigues
Agmatine is an endogenous neuromodulator that has been shown to have antidepressant-like properties. We have previously demonstrated that it can induce a rapid increase in BDNF levels after acute administration, suggesting that agmatine may be a fast-acting antidepressant. To investigate this hypothesis, the present study evaluated the effects of a single administration of agmatine in mice subjected to chronic unpredictable stress (CUS), a model of depression responsive only to chronic treatment with conventional antidepressants...
October 12, 2016: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/27735126/sulforaphane-epigenetically-enhances-neuronal-bdnf-expression-and-trkb-signaling-pathways
#18
Jisung Kim, Siyoung Lee, Bo-Ryoung Choi, Hee Yang, Youjin Hwang, Jung Han Yoon Park, Frank M LaFerla, Jung-Soo Han, Ki Won Lee, Jiyoung Kim
SCOPE: Brain-derived neurotrophic factor (BDNF) is a neurotrophin that supports the survival of existing neurons and encourages the growth and differentiation of new neurons and synapses. We investigated the effect of sulforaphane, a hydrolysis product of glucoraphanin present in Brassica vegetables, on neuronal BDNF expression and its synaptic signaling pathways. METHODS AND RESULTS: Mouse primary cortical neurons and a triple-transgenic mouse model of Alzheimer's disease (3 × Tg-AD) were used to study the effect of sulforaphane...
October 13, 2016: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27687706/ketamine-induced-inhibition-of-glycogen-synthase-kinase-3-contributes-to-the-augmentation-of-%C3%AE-amino-3-hydroxy-5-methylisoxazole-4-propionic-acid-ampa-receptor-signaling
#19
Eléonore Beurel, Steven F Grieco, Celeste Amadei, Kimberlee Downey, Richard S Jope
OBJECTIVES: Sub-anesthetic doses of ketamine have been found to provide rapid antidepressant actions, indicating that the cellular signaling systems targeted by ketamine are potential sites for therapeutic intervention. Ketamine acts as an antagonist of N-methyl-D-aspartate (NMDA) receptors, and animal studies indicate that subsequent augmentation of signaling by α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors is critical for the antidepressant outcome. METHODS: In this study, we tested if the inhibitory effect of ketamine on glycogen synthase kinase-3 (GSK3) affected hippocampal cell-surface AMPA receptors using immunoblotting of membrane and synaptosomal extracts from wild-type and GSK3 knockin mice...
September 2016: Bipolar Disorders
https://www.readbyqxmd.com/read/27680311/g-csf-improves-cums-induced-depressive-behaviors-through-downregulating-ras-erk-mapk-signaling-pathway
#20
Hui Li, Linjuan-Li, Yaping Wang
Neuronal plasticity in hippocampal neurons is closely related to memory, mood and behavior as well as in the development of depression. Granulocyte colony-stimulating factor (G-CSF) can promote neuronal plasticity and enhance motor skills. However, the function of G-CSF in depression remains poorly understood. In this study, we explored the biological role and potential molecular mechanism of G-CSF on depression-like behaviors. Our results showed that G-CSF was significantly downregulated in the hippocampus of chronic unexpected mild stress (CUMS) rats...
October 28, 2016: Biochemical and Biophysical Research Communications
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