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https://www.readbyqxmd.com/read/28104309/heightened-cortical-excitability-in-aged-rodents-with-memory-impairment
#1
Rebecca P Haberman, Ming Teng Koh, Michela Gallagher
Elevated excitability in the hippocampus has emerged as a key contributor to reduced memory function in aging and in cognitive impairment prodromal to Alzheimer's disease. Here, we investigated the relationship between neural activity and memory in the hippocampus and a connectional cortical network using an aged rat model of individual differences for memory impairment. The expression of cFos was used as a measure of pharmacologically induced neural activity. Aged memory-impaired rats exhibited elevated cFos relative to young adult and aged unimpaired rats in the CA3 subfield of the hippocampus and in several cortical regions including the retrosplenial, parietal, and orbitofrontal cortices...
January 3, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28102468/mutation-of-the-herc-1-ubiquitin-ligase-impairs-associative-learning-in-the-lateral-amygdala
#2
Eva Mª Pérez-Villegas, José V Negrete-Díaz, Mª Elena Porras-García, Rocío Ruiz, Angel M Carrión, Antonio Rodríguez-Moreno, José A Armengol
Tambaleante (tbl/tbl) is a mutant mouse that carries a spontaneous Gly483Glu substitution in the HERC1 (HECT domain and RCC1 domain) E3 ubiquitin ligase protein (HERC1). The tbl/tbl mutant suffers an ataxic syndrome given the almost complete loss of cerebellar Purkinje cells during adult life. More recent analyses have identified alterations at neuromuscular junctions in these mice, as well as in other neurons of the central nervous system, such as motor neurons in the spinal cord, or pyramidal neurons in the hippocampal CA3 region and the neocortex...
January 19, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28100752/differential-vulnerability-of-ca1-versus-ca3-pyramidal-neurons-after-ischemia-possible-relationship-to-sources-of-zn2-accumulation-and-its-entry-into-and-prolonged-effects-on-mitochondria
#3
Yuliya V Medvedeva, Sung G Ji, Hong Z Yin, John H Weiss
: Excitotoxic mechanisms contribute to the degeneration of hippocampal pyramidal neurons after recurrent seizures and brain ischemia. However, susceptibility differs, with CA1 neurons degenerating preferentially after global ischemia and CA3 neurons after limbic seizures. Whereas most studies address contributions of excitotoxic Ca(2+) entry, it is apparent that Zn(2+) also contributes, reflecting accumulation in neurons either after synaptic release and entry through postsynaptic channels or upon mobilization from intracellular Zn(2+)-binding proteins such as metallothionein-III (MT-III)...
January 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28100750/target-dependent-compartmentalization-of-the-corelease-of-glutamate-and-gaba-from-the-mossy-fibers
#4
Emilio J Galván, Rafael Gutiérrez
: The mossy fibers (MFs) corelease glutamate and GABA onto pyramidal cells of CA3 during development, until the end of the third postnatal week. However, the major target cells of the MF are the interneurons of CA3. Therefore, it has been shown that the interneurons of the hilus and stratum lucidum receive this dual monosynaptic input on MF stimulation. Because the plasticity of glutamatergic transmission from the different terminals of the MF is target specific, we here asked whether the corelease of glutamate and GABA was also subjected to a target-dependent compartmentalization...
January 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28100741/control-of-spike-transfer-at-hippocampal-mossy-fiber-synapses-in-vivo-by-gabaa-and-gabab-receptor-mediated-inhibition
#5
Stefano Zucca, Marilena Griguoli, Meryl Malézieux, Noëlle Grosjean, Mario Carta, Christophe Mulle
: Despite extensive studies in hippocampal slices and incentive from computational theories, the synaptic mechanisms underlying information transfer at mossy fiber (mf) connections between the dentate gyrus (DG) and CA3 neurons in vivo are still elusive. Here we used an optogenetic approach in mice to selectively target and control the activity of DG granule cells (GCs) while performing whole-cell and juxtacellular recordings of CA3 neurons in vivo In CA3 pyramidal cells (PCs), mf-CA3 synaptic responses consisted predominantly of an IPSP at low stimulation frequency (0...
January 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28100490/amino-terminal-domains-of-kainate-receptors-determine-the-differential-dependence-on-neto-auxiliary-subunits-for-trafficking
#6
Nengyin Sheng, Yun Stone Shi, Roger A Nicoll
The kainate receptor (KAR), a subtype of glutamate receptor, mediates excitatory synaptic responses at a subset of glutamatergic synapses. However, the molecular mechanisms underlying the trafficking of its different subunits are poorly understood. Here we use the CA1 hippocampal pyramidal cell, which lacks KAR-mediated synaptic currents, as a null background to determine the minimal requirements for the extrasynaptic and synaptic expression of the GluK2 subunit. We find that the GluK2 receptor itself, in contrast to GluK1, traffics to the neuronal surface and synapse efficiently and the auxiliary subunits Neto1 and Neto2 caused no further enhancement of these two trafficking processes...
January 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096497/bdnf-regains-function-in-hippocampal-long-term-potentiation-deficits-caused-by-diencephalic-damage
#7
Lindsey C Vedder, Lisa M Savage
Thiamine deficiency (TD), commonly associated with chronic alcoholism, leads to diencephalic damage, hippocampal dysfunction, and spatial learning and memory deficits. We show a decrease in the magnitude of long-term potentiation (LTP) and paired-pulse facilitation (PPF) at CA3-CA1 synapses, independent of sex, following diencephalic damage induced by TD in rats. Thus, despite a lack of extensive hippocampal cell loss, diencephalic brain damage down-regulates plastic processes within the hippocampus, likely contributing to impaired hippocampal-dependent behaviors...
February 2017: Learning & Memory
https://www.readbyqxmd.com/read/28093558/glutamatergic-synapses-are-structurally-and-biochemically-complex-because-of-multiple-plasticity-processes-long-term-potentiation-long-term-depression-short-term-potentiation-and-scaling
#8
REVIEW
John Lisman
Synapses are complex because they perform multiple functions, including at least six mechanistically different forms of plasticity. Here, I comment on recent developments regarding these processes. (i) Short-term potentiation (STP), a Hebbian process that requires small amounts of synaptic input, appears to make strong contributions to some forms of working memory. (ii) The rules for long-term potentiation (LTP) induction in CA3 have been clarified: induction does not depend obligatorily on backpropagating sodium spikes but, rather, on dendritic branch-specific N-methyl-d-aspartate (NMDA) spikes...
March 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28093241/new-isatin-derivative-inhibits-neurodegeneration-by-restoring-insulin-signaling-in-brain
#9
Meha Fatima Aftab, Shabbir Khan Afridi, Uzma Rasool Mughal, Aneela Karim, Darakhshan Jabeen Haleem, Nurul Kabir, Khalid M Khan, Rahman M Hafizur, Rizwana S Waraich
Diabetes is associated with neurodegeneration. Glycation ensues in diabetes and glycated proteins cause insulin resistance in brain resulting in amyloid plaques and NFTs. Also glycation enhances gliosis by promoting neuroinflammation. Currently there is no therapy available to target neurodegenration in brain therefore, development of new therapy that offers neuroprotection is critical. The objective of this study was to evaluate mechanistic effect of isatin derivative URM-II-81, an anti-glycation agent for improvement of insulin action in brain and inhibition of neurodegenration...
January 13, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28093219/a-mixed-glucocorticoid-mineralocorticoid-receptor-modulator-dampens-endocrine-and-hippocampal-stress-responsivity-in-male-rats
#10
Elizabeth T Nguyen, Joshua Streicher, Sarah Berman, Jody L Caldwell, Valentina Ghisays, Christina M Estrada, Aynara C Wulsin, Matia B Solomon
Aberrant glucocorticoid secretion is implicated in the pathophysiology of stress-related disorders (i.e., depression, anxiety). Glucocorticoids exert biological effects via mineralocorticoid (MR) and glucocorticoid (GR) receptors. Previous data from our laboratory indicate that GR antagonism/modulation (i.e., mifepristone, CORT 108297) regulate endocrine, behavioral, and central stress responses. Because of the dynamic interplay between MR and GR on HPA axis regulation and emotionality, compounds targeting both receptors are of interest for stress-related pathology...
January 13, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28088401/pharmacological-rescue-of-adult-hippocampal-neurogenesis-in-a-mouse-model-of-x-linked-intellectual-disability
#11
Manuela Allegra, Cristina Spalletti, Beatrice Vignoli, Stefano Azzimondi, Irene Busti, Pierre Billuart, Marco Canossa, Matteo Caleo
Oligophrenin-1 (OPHN1) is a Rho GTPase activating protein whose mutations cause X-linked intellectual disability (XLID). How loss of function of Ophn1 affects neuronal development is only partly understood. Here we have exploited adult hippocampal neurogenesis to dissect the steps of neuronal differentiation that are affected by Ophn1 deletion. We found that mice lacking Ophn1 display a reduction in the number of newborn neurons in the dentate gyrus. A significant fraction of the Ophn1-deficient newly generated neurons failed to extend an axon towards CA3, and showed an altered density of dendritic protrusions...
January 11, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28079889/deletion-of-the-bh3-only-protein-noxa-alters-electrographic-seizures-but-does-not-protect-against-hippocampal-damage-after-status-epilepticus-in-mice
#12
Naoki Ichikawa, Mariana Alves, Shona Pfeiffer, Elena Langa, Yasmina E Hernández-Santana, Hidenori Suzuki, Jochen Hm Prehn, Tobias Engel, David C Henshall
Several members of the Bcl-2 gene family are dysregulated in human temporal lobe epilepsy and animal studies show that genetic deletion of some of these proteins influence electrographic seizure responses to chemoconvulsants and associated brain damage. The BH3-only proteins form a subgroup comprising direct activators of Bax-Bak that are potently proapoptotic and a number of weaker proapoptotic BH3-only proteins that act as sensitizers by neutralization of antiapoptotic Bcl-2 family members. Noxa was originally characterized as a weaker proapoptotic, 'sensitizer' BH3-only protein, although recent evidence suggests it too may be potently proapoptotic...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28077511/altered-connectivity-and-synapse-maturation-of-the-hippocampal-mossy-fiber-pathway-in-a-mouse-model-of-the-fragile-x-syndrome
#13
F Scharkowski, Michael Frotscher, David Lutz, Martin Korte, Kristin Michaelsen-Preusse
The Fragile X syndrome (FXS) as the most common monogenetic cause of cognitive impairment and autism indicates how tightly the dysregulation of synapse development is linked to cognitive deficits. Symptoms of FXS include excessive adherence to patterns that point to compromised hippocampal network formation. Surprisingly, one of the most complex hippocampal synapses connecting the dentate gyrus (DG) to CA3 pyramidal neurons has not been analyzed in FXS yet. Intriguingly, we found altered synaptic function between DG and CA3 in a mouse model of FXS (fmr1 knockout [KO]) demonstrated by increased mossy fiber-dependent miniature excitatory postsynaptic current (mEPSC) frequency at CA3 pyramidal neurons together with increased connectivity between granule cells and CA3 neurons...
January 10, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28076384/anti-epileptic-drug-combination-efficacy-in-an-in-vitro-seizure-model-phenytoin-and-valproate-lamotrigine-and-valproate
#14
Kim Det Taing, Terence J O'Brien, David A Williams, Chris R French
In this study, we investigated the relative efficacy of different classes of commonly used anti-epileptic drugs (AEDs) with different mechanisms of action, individually and in combination, to suppress epileptiform discharges in an in vitro model. Extracellular field potential were recorded in 450 μm thick transverse hippocampal slices prepared from juvenile Wistar rats, in which "epileptiform discharges" (ED's) were produced with a high-K+ (8.5 mM) bicarbonate-buffered saline solution. Single and dual recordings in stratum pyramidale of CA1 and CA3 regions were performed with 3-5 MΩ glass microelectrodes...
2017: PloS One
https://www.readbyqxmd.com/read/28070483/increased-hippocampal-activation-in-apoe-4-carriers-and-non-carriers-with-amnestic-mild-cognitive-impairment
#15
Tammy T Tran, Caroline L Speck, Aparna Pisupati, Michela Gallagher, Arnold Bakker
Increased fMRI activation in the hippocampus is recognized as a signature characteristic of the amnestic mild cognitive impairment (aMCI) stage of Alzheimer's disease (AD). Previous work has localized this increased activation to the dentate gyrus/CA3 subregion of the hippocampus and showed a correlation with memory impairments in those patients. Increased hippocampal activation has also been reported in carriers of the ApoE-4 allelic variation independently of mild cognitive impairment although these findings were not localized to a hippocampal subregion...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28069922/mechanisms-of-nmda-receptor-and-voltage-gated-l-type-calcium-channel-dependent-hippocampal-ltp-critically-rely-on-proteolysis-that-is-mediated-by-distinct-metalloproteinases
#16
Grzegorz Wiera, Daria Nowak, Inge Van Hove, Piotr Dziegiel, Lieve Moons, Jerzy W Mozrzymas
: Long-term potentiation (LTP) is widely perceived as a memory substrate and in the hippocampal CA3-CA1 pathway, distinct forms of LTP depend on N-methyl-D-aspartate (NMDA) receptors (nmdaLTP) or L-type voltage-gated calcium channels (vdccLTP). Long-term potentiation is also known to be effectively regulated by extracellular proteolysis that is mediated by various enzymes. Herein, we investigated whether in mice hippocampal slices these distinct forms of LTP are specifically regulated by different metalloproteinases (MMPs)...
January 9, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28067280/increase-in-%C3%AE-tubulin-modifications-in-the-neuronal-processes-of-hippocampal-neurons-in-both-kainic-acid-induced-epileptic-seizure-and-alzheimer-s-disease
#17
Hang Thi Vu, Hiroyasu Akatsu, Yoshio Hashizume, Mitsutoshi Setou, Koji Ikegami
Neurodegeneration includes acute changes and slow-developing alterations, both of which partly involve common cellular machinery. During neurodegeneration, neuronal processes are impaired along with dysregulated post-translational modifications (PTMs) of cytoskeletal proteins. In neuronal processes, tubulin undergoes unique PTMs including a branched form of modification called glutamylation and loss of the C-terminal tyrosine residue and the penultimate glutamic acid residue forming Δ2-tubulin. Here, we investigated the state of two PTMs, glutamylation and Δ2 form, in both acute and slow-developing neurodegenerations, using a newly generated monoclonal antibody, DTE41, which had 2-fold higher affinity to glutamylated Δ2-tubulin, than to unmodified Δ2-tubulin...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28067279/impaired-novelty-acquisition-and-synaptic-plasticity-in-congenital-hyperammonemia-caused-by-hepatic-glutamine-synthetase-deficiency
#18
Aisa N Chepkova, Olga A Sergeeva, Boris Görg, Helmut L Haas, Nikolaj Klöcker, Dieter Häussinger
Genetic defects in ammonia metabolism can produce irreversible damage of the developing CNS causing an impairment of cognitive and motor functions. We investigated alterations in behavior, synaptic plasticity and gene expression in the hippocampus and dorsal striatum of transgenic mice with systemic hyperammonemia resulting from conditional knockout of hepatic glutamine synthetase (LGS-ko). These mice showed reduced exploratory activity and delayed habituation to a novel environment. Field potential recordings from LGS-ko brain slices revealed significantly reduced magnitude of electrically-induced long-term potentiation (LTP) in both CA3-CA1 hippocampal and corticostriatal synaptic transmission...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28065934/brain-cannabinoid-receptor-2-expression-function-and-modulation
#19
REVIEW
De-Jie Chen, Ming Gao, Fen-Fei Gao, Quan-Xi Su, Jie Wu
Cannabis sativa (marijuana) is a fibrous flowering plant that produces an abundant variety of molecules, some with psychoactive effects. At least 4% of the world's adult population uses cannabis annually, making it one of the most frequently used illicit drugs in the world. The psychoactive effects of cannabis are mediated primarily through cannabinoid receptor (CBR) subtypes. The prevailing view is that CB1Rs are mainly expressed in the central neurons, whereas CB2Rs are predominantly expressed in peripheral immune cells...
January 9, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28065873/hyperbaric-oxygen-effects-on-depression-like-behavior-and-neuroinflammation-in-traumatic-brain-injury-rats
#20
Sher-Wei Lim, Kuan-Chin Sung, Yow-Ling Shiue, Che-Chuan Wang, Chung-Ching Chio, Jinn-Rung Kuo
OBJECTIVE: The aim of this study was to determine whether hyperbaric oxygen (HBO) therapy causes attenuation of traumatic brain injury (TBI)-induced depression-like behavior and its associated anti-neuroinflammatory effects after fluid percussion injury. METHODS: Anesthetized male Sprague-Dawley rats were divided into three groups: sham operation + NBA (normobaric air: 21% O2 at 1 absolute atmosphere [ATA]), TBI + NBA, and TBI + HBO (100% O2 at 2.0 ATA). HBO was applied immediately for 60 min/day after TBI for 3 days...
January 5, 2017: World Neurosurgery
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