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https://www.readbyqxmd.com/read/28346765/the-medial-temporal-memory-system-in-down-syndrome-translating-animal-models-of-hippocampal-compromise
#1
Caron A C Clark, Fabian Fernandez, Stella Sakhon, Goffredina Spanò, Jamie O Edgin
Recent studies have highlighted the dentate gyrus as a region of increased vulnerability in mouse models of Down syndrome (DS). It is unclear to what extent these findings are reflected in the memory profile of people with the condition. We developed a series of novel tasks to probe distinct medial temporal functions in children and young adults with DS, including object, spatial, and serial order memory. Relative to mental age-matched controls (n = 45), individuals with DS (n = 28) were unimpaired on subtests involving short-term object or configural recall that was divorced from spatial or temporal contexts...
March 27, 2017: Hippocampus
https://www.readbyqxmd.com/read/28346493/aberrant-neuronal-activity-induced-signaling-and-gene-expression-in-a-mouse-model-of-rasopathy
#2
Franziska Altmüller, Santosh Pothula, Anil Annamneedi, Saeideh Nakhei-Rad, Carolina Montenegro-Venegas, Eneko Pina-Fernández, Claudia Marini, Monica Santos, Denny Schanze, Dirk Montag, Mohammad R Ahmadian, Oliver Stork, Martin Zenker, Anna Fejtova
Noonan syndrome (NS) is characterized by reduced growth, craniofacial abnormalities, congenital heart defects, and variable cognitive deficits. NS belongs to the RASopathies, genetic conditions linked to mutations in components and regulators of the Ras signaling pathway. Approximately 50% of NS cases are caused by mutations in PTPN11. However, the molecular mechanisms underlying cognitive impairments in NS patients are still poorly understood. Here, we report the generation and characterization of a new conditional mouse strain that expresses the overactive Ptpn11D61Y allele only in the forebrain...
March 27, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28346482/24s-hydroxycholesterol-and-25-hydroxycholesterol-differentially-impact-hippocampal-neuronal-survival-following-oxygen-glucose-deprivation
#3
Min-Yu Sun, Amanda Taylor, Charles F Zorumski, Steven Mennerick
N-methyl-D-aspartate receptors (NMDARs), a major subtype of glutamate receptor mediating excitatory transmission throughout the CNS, participate in ischemia-induced neuronal death. Unfortunately, undesired side effects have limited the strategy of inhibiting/blocking NMDARs as therapy. Targeting endogenous positive allosteric modulators of NMDAR function may offer a strategy with fewer downsides. Here, we explored whether 24S-hydroxycholesterol (24S-HC), an endogenous positive NMDAR modulator characterized recently by our group, participates in NMDAR-mediated excitotoxicity following oxygen-glucose deprivation (OGD) in primary neuron cultures...
2017: PloS One
https://www.readbyqxmd.com/read/28346453/activity-induced-histone-modifications-govern-neurexin-1-mrna-splicing-and-memory-preservation
#4
Xinlu Ding, Sanxiong Liu, Miaomiao Tian, Wenhao Zhang, Tao Zhu, Dongdong Li, Jiawei Wu, HaiTeng Deng, Yichang Jia, Wei Xie, Hong Xie, Ji-Song Guan
Epigenetic mechanisms regulate the formation, consolidation and reconsolidation of memories. However, the signaling path from neuronal activation to epigenetic modifications within the memory-related brain circuit remains unknown. We report that learning induces long-lasting histone modifications in hippocampal memory-activated neurons to regulate memory stability. Neuronal activity triggers a late-onset shift in Nrxn1 splice isoform choice at splicing site 4 by accumulating a repressive histone marker, H3K9me3, to modulate the splicing process...
March 27, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28346227/reducing-expression-of-synapse-restricting-protein-ephexin5-ameliorates-alzheimer-s-like-impairment-in-mice
#5
Gabrielle L Sell, Thomas B Schaffer, Seth S Margolis
Accumulation of amyloid-β (Aβ) protein may cause synapse degeneration and cognitive impairment in Alzheimer's disease (AD) by reactivating expression of the developmental synapse repressor protein Ephexin5 (also known as ARHGEF15). Here, we have reported that Aβ is sufficient to acutely promote the production of Ephexin5 in mature hippocampal neurons and in mice expressing human amyloid precursor protein (hAPP mice), a model for familial AD that produces high brain levels of Aβ. Ephexin5 expression was highly elevated in the hippocampi of human AD patients, indicating its potential relevance to AD...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28345617/stimulation-of-adult-hippocampal-neurogenesis-by-physical-exercise-and-enriched-environment-is-disturbed-in-a-cadasil-mouse-model
#6
C Klein, S Schreyer, F E Kohrs, P Elhamoury, A Pfeffer, T Munder, B Steiner
In the course of CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), a dysregulated adult hippocampal neurogenesis has been suggested as a potential mechanism for early cognitive decline. Previous work has shown that mice overexpressing wild type Notch3 and mice overexpressing Notch3 with a CADASIL mutation display impaired cell proliferation and survival of newly born hippocampal neurons prior to vascular abnormalities. Here, we aimed to elucidate how the long-term survival of these newly generated neurons is regulated by Notch3...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28344548/gsk-3%C3%AE-overexpression-alters-the-dendritic-spines-of-developmentally-generated-granule-neurons-in-the-mouse-hippocampal-dentate-gyrus
#7
Noemí Pallas-Bazarra, Asta Kastanauskaite, Jesús Avila, Javier DeFelipe, María Llorens-Martín
The dentate gyrus (DG) plays a crucial role in hippocampal-related memory. The most abundant cellular type in the DG, namely granule neurons, are developmentally generated around postnatal day P6 in mice. Moreover, a unique feature of the DG is the occurrence of adult hippocampal neurogenesis, a process that gives rise to newborn granule neurons throughout life. Adult-born and developmentally generated granule neurons share some maturational aspects but differ in others, such as in their positioning within the granule cell layer...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28343962/contextually-mediated-spontaneous-retrieval-is-specific-to-the-hippocampus
#8
Nicole M Long, Michael R Sperling, Gregory A Worrell, Kathryn A Davis, Robert E Gross, Bradley C Lega, Barbara C Jobst, Sameer A Sheth, Kareem Zaghloul, Joel M Stein, Michael J Kahana
Although it is now well established that the hippocampus supports memory encoding [1, 2], little is known about hippocampal activity during spontaneous memory retrieval. Recent intracranial electroencephalographic (iEEG) work has shown that hippocampal activity during encoding predicts subsequent temporal organization of memories [3], supporting a role in contextual binding. It is an open question, however, whether the hippocampus similarly supports contextually mediated processes during retrieval. Here, we analyzed iEEG recordings obtained from 215 epilepsy patients as they performed a free recall task...
March 8, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28343869/spatiotemporal-regulation-of-synaptic-vesicle-fusion-sites-in-central-synapses
#9
Dario Maschi, Vitaly A Klyachko
The number and availability of vesicle release sites at the synaptic active zone (AZ) are critical factors governing neurotransmitter release; yet, these fundamental synaptic parameters have remained undetermined. Moreover, how neural activity regulates the spatiotemporal properties of the release sites within individual central synapses is unknown. Here, we combined a nanoscale imaging approach with advanced image analysis to detect individual vesicle fusion events with ∼27 nm localization precision at single hippocampal synapses under physiological conditions...
March 18, 2017: Neuron
https://www.readbyqxmd.com/read/28343868/medial-prefrontal-cortex-reduces-memory-interference-by-modifying-hippocampal-encoding
#10
Kevin G Guise, Matthew L Shapiro
The prefrontal cortex (PFC) is crucial for accurate memory performance when prior knowledge interferes with new learning, but the mechanisms that minimize proactive interference are unknown. To investigate these, we assessed the influence of medial PFC (mPFC) activity on spatial learning and hippocampal coding in a plus maze task that requires both structures. mPFC inactivation did not impair spatial learning or retrieval per se, but impaired the ability to follow changing spatial rules. mPFC and CA1 ensembles recorded simultaneously predicted goal choices and tracked changing rules; inactivating mPFC attenuated CA1 prospective coding...
March 22, 2017: Neuron
https://www.readbyqxmd.com/read/28343864/diazepam-binding-inhibitor-promotes-stem-cell-expansion-controlling-environment-dependent-neurogenesis
#11
Ionut Dumitru, Angela Neitz, Julieta Alfonso, Hannah Monyer
Plasticity of adult neurogenesis supports adaptation to environmental changes. The identification of molecular mediators that signal these changes to neural progenitors in the niche has remained elusive. Here we report that diazepam binding inhibitor (DBI) is crucial in supporting an adaptive mechanism in response to changes in the environment. We provide evidence that DBI is expressed in stem cells in all neurogenic niches of the postnatal brain. Focusing on the hippocampal subgranular zone (SGZ) and employing multiple genetic manipulations in vivo, we demonstrate that DBI regulates the balance between preserving the stem cell pool and neurogenesis...
March 18, 2017: Neuron
https://www.readbyqxmd.com/read/28343294/neuroprotective-role-of-exogenous-brain-derived-neurotrophic-factor-in-hypoxia-hypoglycemia-induced-hippocampal-neuron-injury-via-regulating-trkb-mir134-signaling
#12
Weidong Huang, Facai Meng, Jie Cao, Xiaobin Liu, Jie Zhang, Min Li
Hypoxic-ischemic brain injury is an important cause of neonatal mortality and morbidity. Brain-derived neurotrophic factor (BDNF) has been reported to play a neuroprotective role in hypoxic-ischemic brain injury; however, the specific effects and mechanism of BDNF on hypoxic-hypoglycemic hippocampal neuron injury remains unknown. The current study investigated the action of BDNF in regulating cerebral hypoxic-ischemic injury by simulating hippocampal neuron ischemia and hypoxia. We found that BDNF, p-Trkb, and miR-134 expression levels decreased, and that exogenous BDNF increased survival and reduced apoptosis in hypoxic-hypoglycemic hippocampal neurons...
March 26, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28342999/hippocampal-ca3-dentate-gyrus-volume-uniquely-linked-to-improvement-in-associative-memory-from-childhood-to-adulthood
#13
Ana M Daugherty, Robert Flinn, Noa Ofen
Associative memory develops into adulthood and critically depends on the hippocampus. The hippocampus is a complex structure composed of subfields that are functionally-distinct, and anterior-posterior divisions along the length of the hippocampal horizontal axis that may also differ by cognitive correlates. Although each of these aspects has been considered independently, here we evaluate their relative contributions as correlates of age-related improvement in memory. Volumes of hippocampal subfields (subiculum, CA1-2, CA3-dentate gyrus) and anterior-posterior divisions (hippocampal head, body, tail) were manually segmented from high-resolution proton density-weighted images in a sample of healthy participants (age 8-25 years)...
March 22, 2017: NeuroImage
https://www.readbyqxmd.com/read/28342972/remodeling-the-th1-polarized-systemic-environment-contributes-to-neurogenesis-and-cognitive-function-via-the-wnt7a-pathway-in-neonatal-mice
#14
YunLong Xu, Fen He, FangFang Qi, Guangqi Yang, FuXiang Zheng, JunHua Yang, Xiao Wang, JunXiu Liu, JunTao Zou
Neonatal Bacillus Calmette-Guérin (BCG) vaccination results in a positive effect on hippocampal neurogenesis and cognition. Serum cytokines are considered to be the chief culprit. In this study, serum from BCG-treated mice was identified as Th1 polarized serum. The serum showed an increased ratio of IFN-γ to IL-4 and decreased levels of TNF-α and IL-6. After Th1 polarized serum was injected intraperitoneally into postnatal mice, the levels of cytokines and ratio of IFN-γ to IL-4 in the serum and hippocampus of postnatal mice showed a similar alteration as those in Th1 polarized serum...
March 22, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/28342965/effects-of-i2-imidazoline-receptor-ir-alkylating-bu99006-in-the-mouse-brain-upregulation-of-nischarin-i1-ir-and-%C3%AE-opioid-receptor-proteins-and-modulation-of-associated-signalling-pathways
#15
Benjamin Keller, Jesús A García-Sevilla
5-isothiocyanato-2-benzofuranyl-2-imidazoline (BU99006) was shown to selectively and irreversibly bind to I2-imidazoline receptors (IRs) in vitro and in vivo, but cell signalling consequences of I2-IR alkylation have not been reported previously. This study assessed by Western blot the effects of BU99006 on nischarin (candidate I1-IR), μ-OR (regulated by nischarin) and associated signalling mediators in the mouse brain. Acute treatment with BU99006 (20 mg/kg, i.p., 1-3 h) led to fast (peak at 1 h) and shortlasting (decline up to 3 h) upregulation of nischarin and μ-OR contents in the hippocampus (less or non-significant effects in cortex) and altered the expression of cytoskeletal β-actin (reduced contents at 3 h)...
March 23, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28342897/dose-response-effect-of-acute-phencyclidine-on-functional-connectivity-and-dopamine-levels-and-their-association-with-schizophrenia-like-symptom-classes-in-rat
#16
Jaakko Paasonen, Raimo A Salo, Jouni Ihalainen, Juuso V Leikas, Katja Savolainen, Marko Lehtonen, Markus M Forsberg, Olli Gröhn
Current drug treatments for schizophrenia (SCZ) can alleviate positive symptoms, but have little effect on the negative symptoms and cognitive deficits that are difficult to translate into preclinical models for drug development. Therefore, we aimed to determine the dose-response effects of acute phencyclidine (PCP, 1.0-5.0 mg/kg) on rat brain connectivity and detect markers for different SCZ-like symptoms. Pharmacological functional magnetic resonance imaging (phMRI) and microdialysis were used to investigate PCP-induced effects on functional connectivity (FC) and dopamine levels, respectively...
March 22, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28342896/neuroprotective-and-axonal-outgrowth-promoting-effects-of-tetramethylpyrazine-nitrone-in-chronic-cerebral-hypoperfusion-rats-and-primary-hippocampal-neurons-exposed-to-hypoxia
#17
Tao Zhang, Jianbo Gu, Liangmiao Wu, Ning Li, Yewei Sun, Pei Yu, Yuqiang Wang, Gaoxiao Zhang, Zaijun Zhang
Chronic cerebral hypoperfusion is an important risk factor for vascular dementia and other brain dysfunctions, for which there are currently no effective medications available. We investigated the neuroprotective and axonal outgrowth promoting effects of tetramethylpyrazine nitrone (TBN) in a permanent bilateral occlusion of the common carotid arteries (2VO) rat model and in primary hippocampal neurons exposed to oxygen glucose deprivation (OGD). At 6th week after 2VO, TBN increased the time spent in novel arms in the Y-maze test and improved the discrimination ratio in object reorganization task...
March 22, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28342823/evidence-that-increased-kcnj6-gene-dose-is-necessary-for-deficits-in-behavior-and-dentate-gyrus-synaptic-plasticity-in-the-ts65dn-mouse-model-of-down-syndrome
#18
Alexander M Kleschevnikov, Jessica Yu, Jeesun Kim, Larisa V Lysenko, Zheng Zhen, Y Eugene Yu, William C Mobley
Down syndrome (DS), trisomy 21, is caused by increased dose of genes present on human chromosome 21 (HSA21). The gene-dose hypothesis argues that a change in the dose of individual genes or regulatory sequences on HSA21 is necessary for creating DS-related phenotypes, including cognitive impairment. We focused on a possible role for Kcnj6, the gene encoding Kir3.2 (Girk2) subunits of a G-protein-coupled inwardly-rectifying potassium channel. This gene resides on a segment of mouse Chromosome 16 that is present in one extra copy in the genome of the Ts65Dn mouse, a well-studied genetic model of DS...
March 22, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28342774/hypercapnia-induced-brain-acidosis-effects-and-putative-mechanisms-on-acute-kainate-induced-seizures
#19
Xiu-Yu Shi, Lin-Yan Hu, Meng-Jia Liu, Li-Ping Zou
AIMS: This study investigated the mechanism of the anticonvulsant effects of carbogen containing 5% CO2 in a kainic acid (KA) rat model. MAIN METHODS: Four-week-old Sprague-Dawley rats were divided into four groups: control, carbogen, KA+air, and KA+carbogen. Carbogen containing 5% CO2 was applied immediately after KA injection, and cortical pH was recorded. High-performance liquid chromatography was used to detect the release of γ-aminobutyric acid (GABA) and glutamate...
March 22, 2017: Life Sciences
https://www.readbyqxmd.com/read/28342765/hippocampal-insulin-resistance-and-altered-food-decision-making-as-players-on-obesity-risk
#20
REVIEW
Amanda Brondani Mucellini, Natasha Kim de Oliveira da Fonseca, Gisele Gus Manfro, Patrícia Pelufo Silveira
There are increasing evidences that hippocampus can modulate the decision of what, when and how much to eat, in addition to its already recognized role in learning and memory processes. Insulin also has been linked to brain functions such as feeding behavior and the imbalance of its mechanism of action on hippocampus is being related to cognitive dysfunction. The discussion here is whether changes in insulin action could contribute to intake dysregulation and obesogenic behavior as a primary consequence of impairing hippocampal functioning, aside from the role of this hormone on obesity development through peripheral metabolic pathways...
March 22, 2017: Neuroscience and Biobehavioral Reviews
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