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Journal of Neurochemistry

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https://www.readbyqxmd.com/read/29222951/neuronal-pas-domain-protein-4-npas4-controls-neuronal-homeostasis-in-pentylenetetrazole-induced-epilepsy-through-the-induction-of-homer1a
#1
Wei Shan, Taku Nagai, Motoki Tanaka, Norimichi Itoh, Yoko Furukawa-Hibi, Toshitaka Nabeshima, Masahiro Sokabe, Kiyofumi Yamada
Neuronal intrinsic homeostatic scaling-down of excitatory synapse has been implicated in epilepsy pathogenesis to prevent the neuronal circuits from hyper-excitability. Recent findings suggest a role for neuronal PAS domain protein 4 (Npas4), an activity-dependent neuron-specific transcription factor in epileptogenesis, however, the underlying mechanism by which Npas4 regulates epilepsy remains unclear. We herein propose that limbic seizure activity up-regulates Npas4-homer1a signaling in the hippocampus, thereby contributing to epileptogenesis in mice...
December 9, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29222946/triheptanoin-protects-against-status-epilepticus-induced-hippocampal-mitochondrial-dysfunctions-oxidative-stress-and-neuronal-degeneration
#2
Kah Ni Tan, David Simmons, Catalina Carrasco-Pozo, Karin Borges
Triheptanoin, the triglyceride of heptanoate, is anaplerotic (refills deficient tricarboxylic acid cycle intermediates) via the propionyl-CoA carboxylase (PCC) pathway. It has been shown to be neuroprotective and anticonvulsant in several models of neurological disorders. Here, we investigated the effects of triheptanoin against changes of hippocampal mitochondrial functions, oxidative stress and cell death induced by pilocarpine-induced status epilepticus (SE) in mice. Ten days of triheptanoin pre-treatment did not protect against SE, but it preserved hippocampal mitochondrial functions including state 2, state 3 ADP, state 3 uncoupled respiration, respiration linked to ATP synthesis along with the activities of pyruvate dehydrogenase complex and oxoglutarate dehydrogenase complex 24 h post-SE...
December 9, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29222909/an-emerging-role-of-astrocytes-in-vascular-contributions-to-cognitive-impairment-and-dementia-vcid
#3
REVIEW
Brittani R Price, Christopher M Norris, Pradoldej Sompol, Donna M Wilcock
Vascular contributions to cognitive impairment and dementia (VCID) is understood to be the second most common cause of dementia after Alzheimer's disease (AD), and is also a frequent co-morbidity with AD. While VCID is widely acknowledged as a key contributor to dementia, the mechanistic underpinnings of VCID remain poorly understood. In this review, we address the potential role of astrocytes in the pathophysiology of VCID. The vast majority of the blood vessels in the brain are surrounded by astrocytic end-feet...
December 9, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29222907/the-ameliorative-effect-of-fluoxetine-on-neuroinflammation-induced-by-sleep-deprivation
#4
Maosheng Xia, Xiaowei Li, Li Yang, Jiaan Ren, Guangfeng Sun, Shuang Qi, Alexei Verkhratsky, Baoman Li
It is well known that sleep disorders are harmful to people's health and performance, and growing evidence suggests that sleep deprivation (SD) can trigger neuroinflammation in the brain. The nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome is reported to be relevant to the neuroinflammation induced by SD, but the regulatory signaling that governs the NLRP3 inflammasome in SD is still unknown. Meanwhile, whether the regulatory action of antidepressants in astrocytes could affect the neuroinflammation induced by SD also remains obscure...
December 9, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29210076/in-vitro-effect-of-antiretroviral-drugs-on-cultured-primary-astrocytes-analysis-of-neurotoxicity-and-matrix-metalloproteinase-inhibition
#5
Tiziana Latronico, Ilaria Pati, Rossana Ciavarella, Anna Fasano, Fabio Mengoni, Miriam Lichtner, Vincenzo Vullo, Claudio Maria Mastroianni, Grazia Maria Liuzzi
There is little information available on the possible toxic effects that antiretroviral (ARV) drugs used for the treatment of human immunodeficiency virus (HIV)-infected subjects, may have on the central nervous system (CNS) resident cells. Moreover, it is unclear whether the efficacy of the ARV drugs may also be due to their ability to exert extravirological effects on factors responsible for the development of HIV brain injury, e.g. matrix metalloproteinases (MMPs). This study investigates the toxicity of three different ARV drugs and on their ability to modulate levels and expression of gelatinases A (MMP-2) and B (MMP-9) in astrocytes...
December 6, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29210074/white-matter-degeneration-in-vascular-and-other-ageing-related-dementias
#6
REVIEW
Yoshika Hase, Karen Horsburgh, Masafumi Ihara, Raj N Kalaria
Advances in neuroimaging have enabled greater understanding of the progression of cerebral degenerative processes associated with ageing-related dementias. Leukoaraiosis or rarefied white matter (WM) originally described on computed tomography is one of the most prominent changes which occurs in older age. White matter hyperintensities (WMH) evident on magnetic resonance imaging have become commonplace to describe WM changes in relation to cognitive dysfunction, types of stroke injury, cerebral small vessel disease and neurodegenerative disorders including Alzheimer's disease...
December 6, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29210072/chemical-hypoxia-induced-integrated-stress-response-activation-in-oligodendrocytes-is-mediated-by-the-transcription-factor-nuclear-factor-erythroid-derived-2-like-2-nrf2
#7
Nico Teske, Annette Liessem, Felix Fischbach, Tim Clarner, C Beyer, Christoph Wruck, Athanassios Fragoulis, Simone C Tauber, Marion Victor, Markus Kipp
The extent of remyelination in multiple sclerosis (MS) lesions is often incomplete. Injury to oligodendrocyte progenitor cells can be a contributing factor for such incomplete remyelination. The precise mechanisms underlying insufficient repair remain to be defined, but oxidative stress appears to be involved. Here, we used immortalized oligodendrocyte cell lines as model systems to investigate a causal relation of oxidative stress and endoplasmic reticulum stress signaling cascades. OLN93 and OliNeu cells were subjected to chemical hypoxia by blocking the respiratory chain at various levels...
December 6, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29205377/adenosine-a2a-receptors-are-required-for-glutamate-mglur5-and-dopamine-d1-receptor-evoked-erk1-2-phosphorylation-in-rat-hippocampus-involvement-of-nmda-receptor
#8
Paraskevi Krania, Eleni Dimou, Maria Bantouna, Stylianos Kouvaros, Eirini Tsiamaki, Costas Papatheodoropoulos, Konstantinos Sarantis, Fevronia Angelatou
Interaction between mGluR5 and NMDA receptors (NMDAR) is vital for synaptic plasticity and cognition. We recently demonstrated that stimulation of mGluR5 enhances NMDAR-responses in hippocampus by phosphorylating NR2B(Tyr1472) subunit, and this reaction was enabled by adenosine A2A receptors(A2A R) (Sarantis et al.2015). In this study, by using in vitro phosphorylation and western blot analysis in hippocampal slices of male Wistar rats, we show, that mGluR5 stimulation or mGluR5/NMDARs co-stimulation, synergistically activate ERK1/2 signaling leading to c-Fos expression...
December 5, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29205357/hexokinase-2-dependent-hyperglycolysis-driving-microglial-activation-contributes-to-ischemic-brain-injury
#9
Yuan Li, Bingzheng Lu, Longxiang Sheng, Zhu Zhu, Hongjiaqi Sun, Yuwei Zhou, Yang Yang, Dongdong Xue, Wenli Chen, Xuyan Tian, Yun Du, Min Yan, Wenbo Zhu, Fan Xing, Kai Li, Suizhen Lin, Pengxin Qiu, Xingwen Su, Yijun Huang, Guangmei Yan, Wei Yin
Hyperglycolysis, observed within the penumbra zone during brain ischemia, was shown to be detrimental for tissue survival due to lactate accumulation and reactive oxygen species (ROS) overproduction in clinical and experimental settings. Recently, mounting evidence suggests that glycolytic reprogramming and induced metabolic enzymes can fuel the activation of peripheral immune cells. However, the possible roles and details regarding hyperglycolysis in neuroinflammation during ischemia are relatively poorly understood...
December 5, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29193080/neuroprotection-mediated-post-ischemically-by-a-non-peptidic-%C3%AE-opioid-receptor-agonist-tan-67-in-ischemic-stroke-mice-is-associated-with-altered-amyloid-precursor-protein-expression-maturation-and-processing
#10
Jia-Wei Min, Yanying Liu, David Wang, Fangfang Qiao, Hongmin Wang
Tan-67 is a selective non-peptidic δ-opioid receptor (DOR) agonist that confers neuroprotection against cerebral ischemia/reperfusion (I/R)-caused neuronal injury in pre-treated animals. In this study, we examined whether post-ischemic administration of Tan-67 in stroke mice is also neuroprotective and whether the treatment affects expression, maturation and processing of the amyloid precursor protein (APP). A focal cerebral I/R model in mice was induced by middle cerebral artery occlusion for 1 hour (h) and Tan-67 (1...
November 29, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29193067/the-role-of-s-nitrosylation-of-kainate-type-of-ionotropic-glutamate-receptor-2-in-epilepsy-induced-by-kainic-acid
#11
Linxiao Wang, Yanyan Liu, Rulan Lu, Guoying Dong, Xia Chen, Wenwei Yun, Xianju Zhou
Epilepsy is a chronic brain disease affecting millions of individuals. Kainate receptors (KARs),especially kainate-type of ionotropic glutamate receptor 2 (GluK2), play an important role in epileptogenesis. Recent data showed GluK2 could undergo post-translational modifications in terms of S-nitrosylation (SNO), and affect the signaling pathway of cell death in cerebral ischemia-reperfusion. However, it is unclear whether S-nitrosylation of GluK2 (SNO-GluK2) contributes to cell death induced by epilepsy. Here we report that kainic acid (KA)-induced SNO-GluK2 is mediated by GluK2 itself, regulated by neuronal nitric oxide synthase (nNOS) and the level of cytoplasmic calcium in vivo and in vitro hippocampus neurons...
November 29, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29178418/dense-core-vesicle-biogenesis-and-exocytosis-in-neurons-lacking-chromogranins-a-and-b
#12
Natalia Dominguez, Jan Rt van Weering, Ricardo Borges, Ruud F Toonen, Matthijs Verhage
Chromogranin A and B (Cgs) are considered to be master regulators of cargo sorting for the regulated secretory pathway (RSP) and Dense-Core Vesicle (DCV) biogenesis. To test this, we analyzed the release of NPY-pHluorin, a live RSP reporter, and the distribution, number and appearance of DCVs, in mouse hippocampal neurons lacking expression of CHGA and CHGB genes. qRT-PCR analysis showed that expression of other granin family members was not significantly altered in CgA/B-/- neurons. As synaptic maturation of developing neurons depends on secretion of trophic factors in the RSP, we first analyzed neuronal development in standardized neuronal cultures...
November 27, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29178334/suppression-of-oxidative-phosphorylation-confers-resistance-against-bevacizumab-in-experimental-glioma
#13
Jule A Eriksson, Christina Wanka, Michael C Burger, Hans Urban, Ines Hartel, Janusz von Renesse, Patrick N Harter, Michel Mittelbronn, Joachim P Steinbach, Johannes Rieger
Although bevacizumab initially shows high response rates in gliomas and other tumors, therapy resistance usually develops later. Because antiangiogenic agents are supposed to induce hypoxia, we asked whether rendering glioma cells independent of oxidative phosphorylation modulates their sensitivity against hypoxia and bevacizumab. LNT-229 glioma cells without functional mitochondria (rho0 ) and control (rho+ ) cells were generated. LNT-229 rho0 -cells displayed reduced expression of oxidative phosphorylation-related genes and diminished oxygen consumption...
November 27, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29168892/functional-properties-of-dopamine-transporter-oligomers-after-copper-linking
#14
Juan Zhen, Maarten E A Reith
Although it is universally accepted that dopamine transporters (DATs) exist in monomers, dimers and tetramers (i.e. dimers of dimers), it is not known whether the oligomeric organization of DAT is a prerequisite for its ability to take up dopamine (DA), or whether each DAT protomer-the subunit of quaternary structure- functions independently in terms of DA translocation. In the present work copper phenanthroline (CuP) was used to selectively target surface DAT: increasing concentrations of CuP gradually cross-linked natural DAT dimers in LLC-PK1 cells stably expressing hDAT and thereby reduced DA uptake functionality until all surface DATs were inactivated...
November 23, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29168882/fibroblast-growth-factor-2-regulates-activity-and-gene-expression-of-human-postmitotic-excitatory-neurons
#15
Shweta Gupta, Tanya M-Redmond, Fan Meng, Andrew Tidball, Huda Akil, Stanley Watson, Jack M Parent, Michael Uhler
Many neuropsychiatric disorders are thought to result from subtle changes in neural circuit formation. We used human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) to model mature, postmitotic excitatory neurons and examine effects of FGF2. FGF2 gene expression is known to be altered in brain regions of major depressive disorder (MDD) patients and FGF2 has anti-depressive effects in animal models of depression. We generated stable inducible neurons (siNeurons) conditionally expressing human neurogenin 2 (NEUROG2) to generate a homogenous population of post-mitotic excitatory neurons and study the functional as well as the transcriptional effects of FGF2...
November 23, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29168166/new-tool-to-tackle-alzheimer-s-disease-amyloid-%C3%AE-protofibril-selective-antibody-absl-an-editorial-highlight-for-the-conformational-epitope-for-a-new-a%C3%AE-42-protofibril-selective-antibody-partially-overlaps-with-the-peptide-n-terminal-region-on-doi-10-1111-jnc
#16
EDITORIAL
Elek Molnár
This Editorial highlights a study by Colvin et al. (2017) in the current issue of Journal of Neurochemistry, in which the authors describe the development and characterisation of a new rabbit antibody (termed antibody St. Louis; AbSL) that preferentially recognises amyloid-β (Aβ) protein 42 (Aβ42) protofibrils over other Aβ species.
November 23, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29164620/repair-gene-mgmt-is-controlled-by-sp1-and-upregulated-by-glucocorticoids-but-not-by-temozolomide-and-radiation
#17
Dorthe Aasland, Thomas R Reich, Maja T Tomicic, Olivier J Switzeny, Bernd Kaina, Markus Christmann
Therapy of malignant glioma relies on treatment with the O(6) -methylating agent temozolomide (TMZ) concomitant with ionizing radiation followed by adjuvant TMZ. For the treatment of recurrences DNA chloroethylating drugs are also used. The main killing lesion induced by these drugs is O(6) -alkylguanine. Since this damage is repaired by O(6) -methylguanine-DNA methyltransferase (MGMT), the repair enzyme represents the most important factor of drug resistance, limiting the therapy of malignant high-grade gliomas...
November 22, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29164616/protection-against-%C3%AE-amyloid-neurotoxicity-by-a-non-toxic-endogenous-n-terminal-%C3%AE-amyloid-fragment-and-its-active-hexapeptide-core-sequence
#18
Kelly H Forest, Naghum Alfulaij, Komal Arora, Ruth Taketa, Tessi Sherrin, Cedomir Todorovic, James L M Lawrence, Gene T Yoshikawa, Ho-Leung Ng, Victor J Hruby, Robert A Nichols
High levels (μM) of beta amyloid (Aβ) oligomers are known to trigger neurotoxic effects, leading to synaptic impairment, behavioral deficits and apoptotic cell death. The hydrophobic C-terminal domain of Aβ, together with sequences critical for oligomer formation, is essential for this neurotoxicity. However, Aβ at low levels (pM-nM) has been shown to function as a positive neuromodulator and this activity resides in the hydrophilic N-terminal domain of Aβ. An N-terminal Aβ fragment (1-15/16), found in cerebrospinal fluid, was also shown to be a highly active neuromodulator and to reverse Aβ-induced impairments of long-term potentiation...
November 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29164613/calmodulin-like-skin-protein-protects-against-spatial-learning-impairment-in-a-mouse-model-of-alzheimer-disease
#19
Shinya Kusakari, Mikiro Nawa, Katsuko Sudo, Masaaki Matsuoka
Humanin and calmodulin-like skin protein (CLSP) inhibits Alzheimer disease (AD)-related neuronal cell death via the heterotrimeric humanin receptor in vitro. It has been suggested that CLSP is a central agonist of the heterotrimeric humanin receptor in vivo. To investigate the role of CLSP in the AD pathogenesis in vivo, we generated mouse CLSP-1 transgenic mice, crossed them with the APPswe/PSEN1dE9 mice, a model mouse of AD, and examined the effect of CLSP overexpression on the pathological phenotype of the AD mouse model...
November 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29164610/shared-pathological-pathways-of-alzheimer-s-disease-with-specific-comorbidities-current-perspectives-and-interventions
#20
REVIEW
Christiane M Nday, Despoina Eleftheriadou, Graham Jackson
Alzheimer's disease (AD) belongs to one of the most multifactorial, complex and heterogeneous morbidity-leading disorders. Despite the extensive research in the field, AD pathogenesis is still at some extend obscure. Mechanisms linking AD with certain comorbidities, namely diabetes mellitus, obesity and dyslipidemia, are increasingly gaining importance, mainly due to their potential role in promoting AD development and exacerbation. Their exact cognitive impairment trajectories, however, remain to be fully elucidated...
November 21, 2017: Journal of Neurochemistry
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