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Journal of Neurochemistry

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https://www.readbyqxmd.com/read/28734089/dementia-risk-and-prevention-by-targeting-modifiable-vascular-risk-factors
#1
REVIEW
Sana Tariq, Philip A Barber
The incidence of dementia is expected to double in the next 20 years and will contribute to heavy social and economic burden. Dementia is caused by neuronal loss that leads to brain atrophy years before symptoms manifest. Currently, no cure exists and extensive efforts are being made to mitigate cognitive impairment in late life in order to reduce the burden on patients, caregivers, and society. The most common type of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) often co-exists in the brain and shares common, modifiable risk factors, which are targeted in numerous secondary prevention trials...
July 22, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28722769/promoter-iv-bdnf-deficiency-disturbs-cholinergic-gene-expression-of-chrna5-chrm2-and-chrm5-effects-of-drug-and-environmental-treatments
#2
Kazuko Sakata, Abigail E Overacre
Brain-derived neurotrophic factor (BDNF) promotes maturation of cholinergic neurons. However, how activity-dependent BDNF expression affects specific cholinergic gene expression remains unclear. This study addressed this question by determining mRNA levels of 22 acetylcholine receptor subunits, the choline transporter (CHT), and the choline acetyltransferase (ChAT) in mice deficient in activity-dependent BDNF via promoter IV (KIV) and control wild-type mice. Quantitative RT-PCR revealed significant reductions in nicotinic acetylcholine receptor alpha 5 (CHRNA5) in the frontal cortex and hippocampus and M5 muscarinic acetylcholine receptor (CHRM5) in the hippocampus, but significant increases in M2 muscarinic acetylcholine receptor (CHRM2) in the frontal cortex of KIV mice compared to wild-type mice...
July 19, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28722750/protein-kinase-d-exerts-neuroprotective-functions-during-oxidative-stress-via-nuclear-factor-kappab-independent-signaling-pathways
#3
Hanna Liliom, Krisztián Tárnok, Zsófia Ábrahám, Bence Rácz, Angelika Hausser, Katalin Schlett
Members of the protein kinase D (PKD) family of serine/threonine kinases are known to exert diverse roles in neuronal stress responses. Here we show the transient activation and nuclear translocation of endogenous PKD upon oxidative stress induced by H2 O2 treatment in primary neuronal cultures. Using pharmacological inhibition we show that PKD activity protects neurons from oxidative stress induced cell death. Although members of the canonical NFκB pathway were phosphorylated upon H2 O2 treatment, it was found that the neuronal response to oxidative stress is not executed through the nuclear translocation and activity of RelA...
July 19, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28722749/rho-associated-protein-kinases-as-therapeutic-targets-for-both-vascular-and-parenchymal-pathologies-in-alzheimer-s-disease
#4
REVIEW
Aaron Y Lai, JoAnne McLaurin
The causes of late-onset Alzheimer's disease are unclear and likely multifactorial. Rho-associated protein kinases (ROCKs) are ubiquitously expressed signaling messengers that mediate a wide array of cellular processes. Interestingly, they play an important role in several vascular and brain pathologies implicated in Alzheimer's etiology, including hypertension, hypercholesterolemia, blood-brain barrier disruption, oxidative stress, deposition of vascular and parenchymal amyloid-beta peptides, tau hyperphosphorylation, and cognitive decline...
July 19, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28707700/deleting-the-arntl-clock-gene-in-the-granular-layer-of-the-mouse-cerebellum-impact-on-the-molecular-circadian-clockwork
#5
Tenna Bering, Mikkel Bloss Carstensen, Martin Fredensborg Rath
The suprachiasmatic nucleus houses the central circadian clock and is characterized by the timely regulated expression of clock genes. However, neurons of the cerebellar cortex also contain a circadian oscillator with circadian expression of clock genes being controlled by the suprachiasmatic nucleus. It has been suggested that the cerebellar circadian oscillator is involved in food anticipation, but direct molecular evidence of the role of the circadian oscillator of the cerebellar cortex is currently unavailable...
July 14, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28700094/regulation-of-synaptic-acetylcholine-concentrations-by-acetylcholine-transport-in-rat-striatal-cholinergic-transmission
#6
Ikunobu Muramatsu, Junsuke Uwada, Takayoshi Masuoka, Hatsumi Yoshiki, Kiyonao Sada, Kung-Shing Lee, Matomo Nishio, Takaharu Ishibashi, Takanobu Taniguchi
In addition to hydrolysis by acetylcholine esterase (AChE), acetylcholine (ACh) is also directly taken up into brain tissues. In the present study, we examined whether the uptake of ACh is involved in the regulation of synaptic ACh concentrations. Superfusion experiments with rat striatal segments pre-incubated with [(3) H]choline were performed using an ultra-mini superfusion vessel, which was developed to minimize superfusate retention within the vessel. Hemicholinium-3 (HC-3) at concentrations less than 1 μM, selectively inhibited the uptake of [(3) H]choline by the high affinity-choline transporter 1 (CHT1) and had no effect on basal and electrically evoked [(3) H]efflux in superfusion experiments...
July 12, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28700093/interleukin-10-release-from-astrocytes-suppresses-neuronal-apoptosis-via-the-tlr2-nf%C3%AE%C2%BAb-pathway-in-a-neonatal-rat-model-of-hypoxic-ischemic-brain-damage
#7
Mu Lan He, Ze Yu Lv, Xia Shi, Ting Yang, Yun Zhang, Ting-Yu Li, Jie Chen
The biological function of Interleukin-10 (IL-10) and the relationship between IL-10 secretion and the Toll-like receptor 2 (TLR2) expression levels in the central nervous system following hypoxic-ischemic brain damage (HIBD) are poorly understood. Here, we intend to elucidate the biological function and mechanism of IL-10 secretion following HIBD. In the current study, we used a neonatal rat model of HIBD and found that rats injected with adeno-associated virus (AAV)-IL-10-shRNA (short hairpin RNA) exhibited partially impaired learning and memory function compared to rats administered AAV-control-shRNA...
July 12, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28700081/spinal-nociceptive-circuit-analysis-with-recombinant-adeno-associated-viruses-the-impact-of-serotypes-and-promoters
#8
Karen Haenraets, Edmund Foster, Helge Johannssen, Vinnie Kandra, Noemie Frezel, Timothy Steffen, Valeria Jaramillo, Jean-Charles Paterna, Hanns Ulrich Zeilhofer, Hendrik Wildner
Recombinant adeno-associated virus (rAAV) vector-mediated gene transfer into genetically defined neuron subtypes has become a powerful tool to study the neuroanatomy of neuronal circuits in the brain and to unravel their functions. More recently this methodology has also become popular for the analysis of spinal cord circuits. To date a variety of naturally occurring AAV serotypes and genetically modified capsid variants are available but transduction efficiency in spinal neurons, target selectivity and the ability for retrograde tracing are only incompletely characterized...
July 12, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28695568/prmt1-regulates-astrocytic-differentiation-of-embryonic-neural-stem-precursor-cells
#9
Mizuki Honda, Kinichi Nakashima, Sayako Katada
Arginine methylation is a posttranslational modification which is catalyzed by protein arginine methyltransferases (PRMTs). Here, we report that PRMT1 is highly expressed in neural stem/precursor cells (NS/PCs) of mouse embryos, and knockdown of PRMT1 in NS/PCs suppresses the generation of astrocytes. The luciferase assay demonstrated that knockdown of PRMT1 inhibits activation of the promoter of a typical astrocytic marker gene, glial fibrillary acidic protein (Gfap), in NS/PCs. The transcription factor signal transducer and activator of transcription 3 (STAT3) is known to generally be critical for astrocytic differentiation of NS/PCs...
July 11, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28677324/prevention-of-cognitive-impairment-scientific-guidance-and-windows-of-opportunity
#10
REVIEW
Philip B Gorelick
Cognitive impairment of later life is an important medical and public health challenge. Worldwide it is estimated that the number of persons with dementia will continue to increase, especially in low- and middle-income countries. An important public health challenge relates to the prevention of cognitive decline and dementia. Specifically, is it possible to maintain cognitive vitality or prevent or slow cognitive decline? In this opinion-based piece, I review United States-based guidance statements for maintenance of cognition and select single and multidomain trials designed to preserve cognitive function...
July 5, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28677143/-the-physiological-role-of-the-amyloid-precursor-protein-app-as-an-adhesion-molecule-in-the-developing-nervous-system
#11
REVIEW
Lucas J Sosa, Alfredo Caceres, Sebastián Dupraz, Mariana Oksdath, Santiago Quiroga, Alfredo Lorenzo
The amyloid precursor protein (APP) is a type I transmembrane glycoprotein better known for its participation in the physiopathology of Alzheimer disease as the source of the beta amyloid fragment. However, the physiological functions of the full length protein and its proteolytic fragments have remained elusive. APP was first described as a cell-surface receptor; nevertheless, increasing evidence highlighted APP as a cell adhesion molecule (CAM). In this review, we will focus on the current knowledge of the physiological role of APP as a CAM and its involvement in key events of neuronal development, such as migration, neurite outgrowth, growth cone pathfinding and synaptogenesis...
July 5, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28677119/atp-evokes-ca-2-signals-in-cultured-foetal-human-cortical-astrocytes-entirely-through-g-protein-coupled-p2y-receptors
#12
Margit S Muller, Colin W Taylor
Extracellular ATP plays important roles in coordinating the activities of astrocytes and neurons, and aberrant signalling is associated with neurodegenerative diseases. In rodents, ATP stimulates opening of Ca(2+) -permeable channels formed by P2X receptor subunits in the plasma membrane. It is widely assumed, but not verified, that P2X receptors also evoke Ca(2+) signals in human astrocytes. Here we directly assess this hypothesis. We showed that cultured foetal cortical human astrocytes express mRNA for several P2X receptor subunits (P2X4 , P2X5 , P2X6 ) and G-protein-coupled P2Y receptors (P2Y1 , P2Y2 , P2Y6 , P2Y11 )...
July 5, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28675567/a-modulatory-role-of-the-rax-homeobox-gene-in-mature-pineal-gland-function-investigating-the-photoneuroendocrine-circadian-system-of-a-rax-conditional-knockout-mouse
#13
Kristian Rohde, Tenna Bering, Takahisa Furukawa, Martin Fredensborg Rath
The retinal and anterior neural fold homeobox gene (Rax) controls development of the eye and the forebrain. Postnatal expression of Rax in the brain is restricted to the pineal gland, a forebrain structure devoted to melatonin synthesis. The role of Rax in pineal function is unknown. In order to investigate the role of Rax in pineal function while circumventing forebrain abnormalities of the global Rax knockout, we generated an eye and pineal-specific Rax conditional knockout mouse. Deletion of Rax in the pineal gland did not affect morphology of the gland, suggesting that Rax is not essential for pineal gland development...
July 4, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28670737/a-human-scfv-antibody-that-targets-and-neutralizes-high-molecular-weight-pathogenic-amyloid-%C3%AE-oligomers
#14
Adriano Sebollela, Erika N Cline, Izolda Popova, Kevin Luo, Xiaoxia Sun, Jay Ahn, Milena A Barcelos, Vanessa N Bezerra, Natalia M Lyra E Silva, Jason Patel, Nathalia R Pinheiro, Lei A Qin, Josette M Kamel, Anthea Weng, Nadia DiNunno, Adrian M Bebenek, Pauline T Velasco, Kirsten L Viola, Pascale N Lacor, Sergio T Ferreira, William L Klein
Brain accumulation of soluble oligomers of the amyloid-β peptide (AβOs) is increasingly considered a key early event in the pathogenesis of Alzheimer's disease (AD). A variety of AβO species have been identified, both in vitro and in vivo, ranging from dimers to 24mers and higher-order oligomers. However, there is no consensus in the literature regarding which AβO species are most germane to AD pathogenesis. Antibodies capable of specifically recognizing defined subpopulations of AβOs would be a valuable asset in the identification, isolation, and characterization of AD-relevant AβO species...
July 3, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28665486/uptake-and-metabolism-of-sulphated-steroids-by-the-blood-brain-barrier-in-the-adult-male-rat
#15
M Zeeshan Qaiser, Diana E M Dolman, David J Begley, N Joan Abbott, Mihaela Cazacu-Davidescu, Delia I Corol, Jonathan P Fry
Little is known about the origin of the neuroactive steroids dehydroepiandrosterone sulphate (DHEAS) and pregnenolone sulphate (PregS) in the brain or of their subsequent metabolism. Using rat brain perfusion in situ, we have found (3) H-PregS to enter more rapidly than (3) H-DHEAS and both to undergo extensive (>50%) desulphation within 0.5 min of uptake. Enzyme activity for the steroid sulphatase catalysing this deconjugation was enriched in the capillary fraction of the blood-brain barrier and its mRNA expressed in cultures of rat brain endothelial cells and astrocytes...
June 30, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28664650/social-isolation-stress-and-chronic-glutathione-deficiency-have-a-common-effect-on-the-glutamine-to-glutamate-ratio-and-myo-inositol-concentration-in-the-mouse-frontal-cortex
#16
Alberto Corcoba, Rolf Gruetter, Kim Q Do, João M N Duarte
Environmental stress can interact with genetic predisposition to increase the risk of developing psychopathology. In this work, we tested the hypothesis that social isolation stress interacts with impaired glutathione synthesis and have cumulative effects on the neurochemical profile of the frontal cortex. A mouse model with chronic glutathione deficit induced by knockout (-/-) of the glutamate-cysteine ligase modulatory subunit (Gclm) was exposed to social isolation stress from weaning to post-natal day 65...
June 30, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28653748/adaptive-dynamics-of-the-5-ht-systems-following-chronic-administration-of-selective-serotonin-reuptake-inhibitors-a-meta-analysis
#17
Stefan Fritze, Rainer Spanagel, Hamid R Noori
Selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed antidepressants. However, a major concern is their delayed onset of action, which is hypothesized to be associated with the time required for serotonin (5-HT) autoreceptors to desensitize, which should be reflected by actual neurochemical changes. Numerous in vivo microdialysis studies have been published that report on 5-HT levels in different brain sites following SSRI administration. Here we performed a meta-analysis on dynamic changes of 5-HT neurotransmission during the course of chronic SSRI treatment...
June 27, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28643372/fine-tuning-perk-signaling-for-neuroprotection
#18
REVIEW
Mark Halliday, Daniel Hughes, Giovanna Mallucci
Protein translation and folding are tightly controlled processes in all cells, by proteostasis, an important component of which is the unfolded protein response (UPR). During periods of endoplasmic reticulum stress due to protein misfolding, the UPR activates a coordinated response in which the PERK branch activation restricts translation, while a variety of genes involved with protein folding, degradation, chaperone expression and stress responses are induced through signaling of the other branches. Chronic overactivation of the UPR, particularly the PERK branch is observed in the brains of patients in a number of protein misfolding neurodegenerative diseases, including Alzheimer's, and Parkinson's diseases and the taopathies...
June 23, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28640985/the-interaction-between-progranulin-and-prosaposin-is-mediated-by-granulins-and-the-linker-region-between-saposin-b-and-c
#19
Xiaolai Zhou, Peter M Sullivan, Lirong Sun, Fenghua Hu
The frontotemporal lobar degeneration (FTLD) protein progranulin (PGRN) is essential for proper lysosomal function. PGRN localizes in the lysosomal compartment within the cell. Prosaposin (PSAP), the precursor of lysosomal saposin activators (saposin A, B, C, D), physically interacts with PGRN. Previously we have shown that PGRN and PSAP facilitate each other's lysosomal trafficking. Here we report that the interaction between PSAP and PGRN requires the linker region of saposin B and C (BC linker). PSAP protein with the BC linker mutated fails to interact with PGRN and target PGRN to lysosomes in the biosynthetic and endocytic pathways...
June 22, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28640931/ischemia-responsive-protein-94-is-a-key-mediator-of-ischemic-neuronal-injury-induced-microglial-activation
#20
Rajiv Tikamdas, Sarthak Singhal, Ping Zhang, Justin A Smith, Eric G Krause, Stanley M Stevens, Sihong Song, Bin Liu
Neuroinflammation, especially activation of microglia, the key immune cells in the brain, has been proposed to contribute to the pathogenesis of ischemic stroke. However, the dynamics and the potential mediators of microglial activation following ischemic neuronal injury are not well understood. In this study, using oxygen/glucose deprivation and reoxygenation (OGD/R) with neuronal and microglial cell cultures as an in vitro model of ischemic neuronal injury, we set out to identify neuronal factors released from injured neurons that are capable of inducing microglial activation...
June 22, 2017: Journal of Neurochemistry
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