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Santosh R Alluri, Patrick J Riss
We report the synthesis, radiosynthesis, and characterization of a radioligand for poly(ADP-ribose) polymerase (PARP). PARP is of central importance in cell homeostasis, neuroplasticity, and neurodegeneration in the brain. A radiolabeled PARP inhibitor was developed and used for autoradiographic quantification of PARP protein concentration in wild-type and transgenic rodent brains ex vivo in high resolution. The binding of [3 H]rucaparib was found to be confined to PARP-expressing domains, for example, cerebellar cortex or hippocampal regions in both models...
March 16, 2018: ACS Chemical Neuroscience
Yuanyuan Wang, Qinwen Wang, Xiaoming Bao, Yanfei Ding, Jieyi Shentu, Wei Cui, Xiaowei Chen, Xiaofei Wei, Shujun Xu
Taxifolin is a potent flavonoid with anti-inflammatory activity. Taxifolin has been reported to decrease the accumulation of β-amyloid (Aβ), and reduce Aβ-induced neurotoxicity. However, the detail molecular mechanism of taxifolin against Aβ-induced neurotoxicity is largely unknown. In this study, we revealed the protective effects and the underlying mechanisms of taxifolin on the impairments of cognitive function and synapse formation induced by soluble Aβ oligomers. Our results showed that taxifolin prevented neuronal cell death in a concentration-dependent manner...
March 14, 2018: Metabolic Brain Disease
Mary Guaraldi, Thomas B Shea
Objective: We examined genetic and dietary challenge on hippocampal oxidative damage. Mice expressing (ApoE+/+) or lacking apolipoprotein E (ApoE-/-) were maintained on a standard diet or a high fat /high cholesterol (challenge) diet for 11-31 weeks. Similar levels of oxidative species were observed for ApoE+/+ and -/- mice maintained on the basal diet. Method: However, treatment of ApoE-/- homogenates with hydrogen peroxide and iron increased oxidative species by >100%, indicating an equivalent amount of potential oxidative species in latent form...
2018: Open Neurology Journal
Roey Schurr, Mor Nitzan, Ruth Eliahou, Laurent Spinelli, Margitta Seeck, Olaf Blanke, Shahar Arzy
In mental time travel (MTT) one is "traveling" back-and-forth in time, remembering, and imagining events. Despite intensive research regarding memory processes in the hippocampus, it was only recently shown that the hippocampus plays an essential role in encoding the temporal order of events remembered, and therefore plays an important role in MTT. Does it also encode the temporal relations of these events to the remembering self? We asked patients undergoing pre-surgical evaluation with depth electrodes penetrating the temporal lobes bilaterally toward the hippocampus to project themselves in time to a past, future, or present time-point, and then make judgments regarding various events...
2018: Frontiers in Computational Neuroscience
Caroline Morel, Tessi Sherrin, Norman J Kennedy, Kelly H Forest, Seda Avcioglu Barutcu, Michael Robles, Ezekiel Carpenter-Hyland, Naghum Alfulaij, Claire L Standen, Robert A Nichols, Morris Benveniste, Roger J Davis, Cedomir Todorovic
The c-Jun N-terminal kinase (JNK) signal transduction pathway is implicated in learning and memory. Here, we examined the role of JNK activation mediated by the JIP1 scaffold protein. We compared male wild-type mice with a mouse model harboring a point mutation in the Jip1 gene that selectively blocks JIP1-mediated JNK activation. These male mutant mice exhibited increased NMDA receptor currents, increased NMDA receptor-mediated gene expression, and a lower threshold for induction of hippocampal long-term potentiation...
March 14, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Huisheng Wu, Chaoliang Tang, Lydia Wai Tai, Weifeng Yao, Peipei Guo, Junmou Hong, Xin Yang, Xinyi Li, Zhao Jin, Jianjuan Ke, Yanlin Wang
Background & Aims:  Ischemic stroke has been ranked the second cause of death in patients worldwide.Inflammation which is activated during cerebral ischemia/reperfusion is an important mechanism leading to brain injury. This study aimed to investigate the effect of flurbiprofen axetil on cerebral I/R injury and the role of inflammation in this process. Methods:  Rats were subjected to sham operation or global cerebral I/R with or without flurbiprofen axetil (5 mg/kg or 10 mg/kg). Global cerebral ischemia was achieved by occlusion of bilateral common carotid arteries combined with hypotension for 20 min followed by reperfusion for 72 h...
March 14, 2018: Bioscience Reports
Vipan K Parihar, Mattia Maroso, Amber Syage, Barrett D Allen, Maria C Angulo, Ivan Soltesz, Charles L Limoli
Of the many perils associated with deep space travel to Mars, neurocognitive complications associated with cosmic radiation exposure are of particular concern. Despite these realizations, whether and how realistic doses of cosmic radiation cause cognitive deficits and neuronal circuitry alterations several months after exposure remains unclear. In addition, even less is known about the temporal progression of cosmic radiation-induced changes transpiring over the duration of a time period commensurate with a flight to Mars...
March 11, 2018: Experimental Neurology
Adrienne M Antonson, Bindu Balakrishnan, Emily C Radlowski, Geraldine Petr, Rodney W Johnson
Maternal infection during pregnancy increases the risk of neurobehavioral problems in offspring. Evidence from rodent models indicates that the maternal immune response to infection can alter fetal brain development, particularly in the hippocampus. However, information on the effects of maternal viral infection on fetal brain development in gyrencephalic species is limited. Thus, the objective of this study was to assess several effects of maternal viral infection in the last one-third of gestation on hippocampal gene expression and development in fetal piglets...
March 14, 2018: Developmental Neuroscience
Hugo Botha, William G Mantyh, Melissa E Murray, David S Knopman, Scott A Przybelski, Heather J Wiste, Jonathan Graff-Radford, Keith A Josephs, Christopher G Schwarz, Walter K Kremers, Bradley F Boeve, Ronald C Petersen, Mary M Machulda, Joseph E Parisi, Dennis W Dickson, Val Lowe, Clifford R Jack, David T Jones
Predicting underlying pathology based on clinical presentation has historically proven difficult, especially in older cohorts. Age-related hippocampal sclerosis may account for a significant proportion of elderly participants with amnestic dementia. Advances in molecular neuroimaging have allowed for detailed biomarker-based phenotyping, but in the absence of antemortem markers of hippocampal sclerosis, cases of mixed pathology remain problematic. We evaluated the utility of 18F-FDG-PET to differentiate flortaucipir tau PET negative from flortaucipir positive amnestic mild cognitive impairment and dementia and used an autopsy confirmed cohort to test the hypothesis that hippocampal sclerosis might account for the observed pattern...
March 12, 2018: Brain: a Journal of Neurology
Tawfeeq Shekh-Ahmad, Ramona Eckel, Sharadha Dayalan Naidu, Maureen Higgins, Masayuki Yamamoto, Albena T Dinkova-Kostova, Stjepana Kovac, Andrey Y Abramov, Matthew C Walker
Hippocampal sclerosis is a common acquired disease that is a major cause of drug-resistant epilepsy. A mechanism that has been proposed to lead from brain insult to hippocampal sclerosis is the excessive generation of reactive oxygen species, and consequent mitochondrial failure. Here we use a novel strategy to increase endogenous antioxidant defences using RTA 408, which we show activates nuclear factor erythroid 2-related factor 2 (Nrf2, encoded by NFE2L2) through inhibition of kelch like ECH associated protein 1 (KEAP1) through its primary sensor C151...
March 12, 2018: Brain: a Journal of Neurology
Vassilios Papaleonidopoulos, Stylianos Kouvaros, Costas Papatheodoropoulos
Hippocampus is importantly involved in dopamine-dependent behaviors and dopamine is a significant modulator of synaptic plasticity in the hippocampus. Moreover, the dopaminergic innervation appears to be disproportionally segregated along the hippocampal longitudinal (dorsoventral) axis with unknown consequences for synaptic plasticity. In this study we examined the actions of endogenously released dopamine and the effects of exogenous D1/D5 dopamine receptor agonists on theta-burst stimulation-induced long-term potentiation (LTP) of field excitatory synaptic potential (fEPSP) at Schaffer collateral-CA1 synapses in slices from dorsal (DH) and ventral hippocampus (VH)...
March 14, 2018: Synapse
Philipp Abe, Hannah M Wüst, Sebastian J Arnold, Serge A van de Pavert, Ralf Stumm
Adult hippocampal neurogenesis is implicated in learning and memory processing. It is tightly controlled at several levels including progenitor proliferation as well as migration, differentiation and integration of new neurons. Hippocampal progenitors and immature neurons reside in the subgranular zone (SGZ) and are equipped with the CXCL12-receptor CXCR4 which contributes to defining the SGZ as neurogenic niche. The atypical CXCL12-receptor CXCR7 functions primarily by sequestering extracellular CXCL12 but whether CXCR7 is involved in adult neurogenesis has not been assessed...
March 14, 2018: Glia
Shahram Saghafi, Lisa Ferguson, Olivia Hogue, Jordan M Gales, Richard Prayson, Robyn M Busch
OBJECTIVE: The International League Against Epilepsy (ILAE) proposed a classification system for hippocampal sclerosis (HS) based on location and extent of hippocampal neuron loss. The literature debates the usefulness of this classification system when studying memory in people with temporal lobe epilepsy (TLE) and determining memory outcome after temporal lobe resection (TLR). This study further explores the relationship between HS ILAE subtypes and episodic memory performance in patients with TLE and examines memory outcomes after TLR...
March 14, 2018: Epilepsia
Kenneth J O'Riordan, Neng-Wei Hu, Michael J Rowan
Synaptic long-term depression (LTD) is believed to underlie critical mnemonic processes in the adult hippocampus. The roles of the metabotropic and ionotropic actions of glutamate in the induction of synaptic LTD by electrical low-frequency stimulation (LFS) in the living adult animal is poorly understood. Here we examined the requirement for metabotropic glutamate (mGlu) and NMDA receptors in LTD induction in anaesthetized adult rats. LTD induction was primarily dependent on NMDA receptors and required the involvement of both the ion channel function and GluN2B subunit of the receptor...
March 13, 2018: Scientific Reports
Ao Shen, Madeline Nieves-Cintron, Yawen Deng, Qian Shi, Dhrubajyoti Chowdhury, Jinyi Qi, Johannes W Hell, Manuel F Navedo, Yang K Xiang
G protein-coupled receptors (GPCRs) transduce pleiotropic intracellular signals in a broad range of physiological responses and disease states. Activated GPCRs can undergo agonist-induced phosphorylation by G protein receptor kinases (GRKs) and second messenger-dependent protein kinases such as protein kinase A (PKA). Here, we characterize spatially segregated subpopulations of β2 -adrenergic receptor (β2 AR) undergoing selective phosphorylation by GRKs or PKA in a single cell. GRKs primarily label monomeric β2 ARs that undergo endocytosis, whereas PKA modifies dimeric β2 ARs that remain at the cell surface...
March 13, 2018: Nature Communications
Katherine D Duncan, Margaret L Schlichting
How does the hippocampus represent interrelated experiences in memory? We review prominent yet seemingly contradictory theoretical perspectives, which propose that the hippocampus distorts experiential representations to either emphasize their distinctiveness or highlight common elements. These fundamentally different kinds of memory representations may be instantiated in the brain via conjunctive separated codes and adaptively differentiated codes on the one hand, or integrated relational codes on the other...
March 10, 2018: Neurobiology of Learning and Memory
Yong-Ku Kim, Byung-Joo Ham, Kyu-Man Han
The etiology of depression is characterized by the interplay of genetic and environmental factors and brain structural alteration. Childhood adversity is a major contributing factor in the development of depression. Interactions between childhood adversity and candidate genes for depression could affect brain morphology via the modulation of neurotrophic factors, serotonergic neurotransmission, or the hypothalamus-pituitary-adrenal (HPA) axis, and this pathway may explain the subsequent onset of depression...
March 10, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
Dong-Dong Shi, Celia M Dong, Leon C Ho, C T W Lam, Xi-Dan Zhou, Ed X Wu, Zhong-Jun Zhou, Xiao-Min Wang, Zhang-Jin Zhang
Chemotherapy-induced cognitive impairment, also known as "chemobrain," is a common side effect. The purpose of this study was to examine whether resveratrol, a natural polyphenol that has nootropic effects, could prevent chemobrain and its underlying mechanisms. Mice received three injections of docetaxel, adriamycin, and cyclophosphamide (DAC) in combination, a common chemotherapy regimen, at two-day intervals within one week. Resveratrol (50 and 100 mg/kg per day) was orally administered for three weeks, beginning one week before the DAC treatment...
March 10, 2018: Neurobiology of Disease
Wei Jiang, Min Guo, Min Gong, Li Chen, Yang Bi, Yun Zhang, Yuan Shi, Ping Qu, Youxue Liu, Jie Chen, Tingyu Li
Our previous studies demonstrated that vitamin A deficiency (VAD) can impair the postnatal cognitive function of rats by damaging the hippocampus. The present study examined the effects of retinoic acid (RA) on apoptosis induced by hypoxic-ischemic damage in vivo and in vitro, and investigated the possible signaling pathway involved in the neuroprotective anti-apoptotic effects of RA. Flow cytometry, immunofluorescence staining and behavioral tests were used to evaluate the neuroprotective and anti-apoptotic effects of RA...
March 13, 2018: Molecular Brain
Yu-Fei Ni, Hao Wang, Qiu-Yan Gu, Fei-Ying Wang, Ying-Jie Wang, Jin-Liang Wang, Bo Jiang
Major depressive disorder has become one of the most serious neuropsychiatric disorders worldwide. However, currently available antidepressants used in clinical practice are ineffective for a substantial proportion of patients and always have side effects. Besides being a lipid-regulating agent, gemfibrozil is an agonist of peroxisome proliferator-activated receptor-α (PPAR-α). We investigated the antidepressant effects of gemfibrozil on C57BL/6J mice using the forced swim test (FST) and tail suspension test (TST), as well as the chronic unpredictable mild stress (CUMS) model of depression...
March 1, 2018: Journal of Psychopharmacology
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