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https://www.readbyqxmd.com/read/29352267/differential-susceptibility-of-striatal-hippocampal-and-cortical-neurons-to-caspase-6
#1
Anastasia Noël, Libin Zhou, Bénédicte Foveau, P Jesper Sjöström, Andréa C LeBlanc
Active cysteinyl protease Caspase-6 is associated with early Alzheimer and Huntington diseases. Higher entorhinal cortex and hippocampal Caspase-6 levels correlate with lower cognitive performance in aged humans. Caspase-6 induces axonal degeneration in human primary neuron cultures and causes inflammation and neurodegeneration in mouse hippocampus, and age-dependent memory impairment. To assess whether Caspase-6 causes damage to another neuronal system, a transgenic knock-in mouse overexpressing a self-activated form of Caspase-6 five-fold in the striatum, the area affected in Huntington disease, and 2...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29351872/low-cortical-iron-and-high-entorhinal-cortex-volume-promote-cognitive-functioning-in-the-oldest-old
#2
Jiri M G van Bergen, Xu Li, Frances C Quevenco, Anton F Gietl, Valerie Treyer, Sandra E Leh, Rafael Meyer, Alfred Buck, Philipp A Kaufmann, Roger M Nitsch, Peter C M van Zijl, Christoph Hock, Paul G Unschuld
The aging brain is characterized by an increased presence of neurodegenerative and vascular pathologies. However, there is substantial variation regarding the relationship between an individual's pathological burden and resulting cognitive impairment. To identify correlates of preserved cognitive functioning at highest age, the relationship between β-amyloid plaque load, presence of small vessel cerebrovascular disease (SVCD), iron-burden, and brain atrophy was investigated. Eighty cognitively unimpaired participants (44 oldest-old, aged 85-96 years; 36 younger-old, aged 55-80 years) were scanned by integrated positron emission tomography-magnetic resonance imaging for assessing beta regional amyloid plaque load (18F-flutemetamol), white matter hyperintensities as an indicator of SVCD (fluid-attenuated inversion recovery-magnetic resonance imaging), and iron load (quantitative susceptibility mapping)...
December 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29344865/isolation-of-distinct-types-of-neurons-from-fresh-brain-tissue-using-laser-microdissection-in-combination-with-high-performance-liquid-chromatography-mass-spectrometry
#3
Luisa Aring, Simone Steinbach, Katrin Marcus, Caroline May
Humans age and the ageing process affects cells in all areas of the human body, including nerve cells within the brain. With advancing age there is also a rise in the probability of developing a neurodegenerative disorder such as, e.g., amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, or Alzheimer's disease. In all these age-related neurodegenerative disorders, distinct neuron populations within specific brain regions are primarily affected. For example, Parkinson's disease is characterized by a slowly progressive degeneration of dopaminergic neurons in the substantia nigra whereas the entorhinal cortex is first affected in Alzheimer's disease...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29341361/parvalbumin-interneuron-mediated-feedforward-inhibition-controls-signal-output-in-the-deep-layers-of-the-perirhinal-entorhinal-cortex
#4
Janske G P Willems, Wytse J Wadman, Natalie L M Cappaert
The perirhinal (PER) and lateral entorhinal (LEC) cortex form an anatomical link between the neocortex and the hippocampus. However, neocortical activity is transmitted through the PER and LEC to the hippocampus with a low probability, suggesting the involvement of the inhibitory network. This study explored the role of interneuron mediated inhibition, activated by electrical stimulation in the agranular insular cortex (AiP), in the deep layers of the PER and LEC. Activated synaptic input by AiP stimulation rarely evoked action potentials in the PER-LEC deep layer excitatory principal neurons, most probably because the evoked synaptic response consisted of a small excitatory and large inhibitory conductance...
January 17, 2018: Hippocampus
https://www.readbyqxmd.com/read/29341318/cognitive-trajectories-and-spectrum-of-neuropathology-in-superagers-the-first-ten-cases
#5
Emily Rogalski, Tamar Gefen, Qinwen Mao, Maureen Connelly, Sandra Weintraub, Changiz Geula, Eileen H Bigio, M-Marsel Mesulam
On average, memory capacity is significantly higher in populations of 50-60 year olds than in populations of 80 year olds. We define SuperAgers as individuals 80 or older whose episodic memory capacity is at least as good as that of cognitively average individuals in their 50s and 60s. SuperAgers therefore have memory capacity that is superior for age. Previous work showed that SuperAgers have greater cortical volumes and greater resistance to age-related cortical atrophy than 'cognitively average' individuals of the same age...
January 17, 2018: Hippocampus
https://www.readbyqxmd.com/read/29340757/comparing-brain-activity-patterns-during-spontaneous-exploratory-and-cue-instructed-learning-using-single-photon-emission-computed-tomography-spect-imaging-of-regional-cerebral-blood-flow-in-freely-behaving-rats
#6
A Mannewitz, J Bock, S Kreitz, A Hess, J Goldschmidt, H Scheich, Katharina Braun
Learning can be categorized into cue-instructed and spontaneous learning types; however, so far, there is no detailed comparative analysis of specific brain pathways involved in these learning types. The aim of this study was to compare brain activity patterns during these learning tasks using the in vivo imaging technique of single photon-emission computed tomography (SPECT) of regional cerebral blood flow (rCBF). During spontaneous exploratory learning, higher levels of rCBF compared to cue-instructed learning were observed in motor control regions, including specific subregions of the motor cortex and the striatum, as well as in regions of sensory pathways including olfactory, somatosensory, and visual modalities...
January 16, 2018: Brain Structure & Function
https://www.readbyqxmd.com/read/29339456/parp-inhibition-prevents-ethanol-induced-neuroinflammatory-signaling-and-neurodegeneration-in-adult-age-rat-brain-slice-cultures
#7
Nuzhath F Tajuddin, Hee-Yong Kim, Michael A Collins
Utilizing rat adult-age hippocampal-entorhinal cortical (HEC) slice cultures we examined the role of poly [ADP-ribose] polymerase (PARP) in binge ethanol's brain inflammatory and neurodegenerative mechanisms. Activated by DNA strand breaks, PARP (principally PARP1 in brain) promotes DNA repair via poly [ADP-ribose] (PAR) products, but PARP overactivation triggers regulated neuronal necrosis, e.g., parthanatos. Previously we found that brain PARP1 levels were upregulated by neurotoxic ethanol binges in adult rats and HEC slices, and PARP inhibitor PJ34 abrogated slice neurodegeneration...
January 16, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29335607/grid-scale-drives-the-scale-and-long-term-stability-of-place-maps
#8
Caitlin S Mallory, Kiah Hardcastle, Jason S Bant, Lisa M Giocomo
Medial entorhinal cortex (MEC) grid cells fire at regular spatial intervals and project to the hippocampus, where place cells are active in spatially restricted locations. One feature of the grid population is the increase in grid spatial scale along the dorsal-ventral MEC axis. However, the difficulty in perturbing grid scale without impacting the properties of other functionally defined MEC cell types has obscured how grid scale influences hippocampal coding and spatial memory. Here we use a targeted viral approach to knock out HCN1 channels selectively in MEC, causing the grid scale to expand while leaving other MEC spatial and velocity signals intact...
January 15, 2018: Nature Neuroscience
https://www.readbyqxmd.com/read/29333481/theta-sequences-of-grid-cell-populations-can-provide-a-movement-direction-signal
#9
Ipshita Zutshi, Jill K Leutgeb, Stefan Leutgeb
It has been proposed that path integration in mammals is performed by the convergence of internally generated speed and directional inputs onto grid cells. Although this hypothesis has been supported by the discovery that head direction, speed, and grid cells are intermixed within entorhinal cortex and by the recent finding that head-direction inputs are necessary for grid firing, many details on how grid cells are generated have remained elusive. For example, analysis of recording data suggests that substituting head direction for movement direction accrues errors that preclude the formation of grid patterns...
October 2017: Current Opinion in Behavioral Sciences
https://www.readbyqxmd.com/read/29324756/associations-of-plasma-clusterin-and-alzheimer-s-disease-related-mri-markers-in-adults-at-mid-life-the-cardia-brain-mri-sub-study
#10
Thaddeus Haight, R Nick Bryan, Osorio Meirelles, Russell Tracy, Myriam Fornage, Melissa Richard, Ilya Nasrallah, Kristine Yaffe, David R Jacobs, Cora Lewis, Pamela Schreiner, Stephen Sidney, Christos Davatzikos, Lenore J Launer
BACKGROUND: Clinical and epidemiological studies of older persons have implicated clusterin in Alzheimer's disease (AD) pathogenesis. In the context of identifying early biomarkers of risk, we examined associations of plasma clusterin and characteristics of AD in middle-aged individuals from the community. MATERIALS AND METHODS: Subjects were 639 cognitively normal individuals (mean age 50 ± 3.5) from the Coronary Artery Risk Development in Young Adults (CARDIA) Brain MRI sub-study...
2018: PloS One
https://www.readbyqxmd.com/read/29323751/-18-f-av-1451-clustering-of-entorhinal-and-cortical-uptake-in-alzheimer-s-disease
#11
Jennifer L Whitwell, Jonathan Graff-Radford, Nirubol Tosakulwong, Stephen D Weigand, Mary Machulda, Matthew L Senjem, Christopher G Schwarz, Anthony J Spychalla, David T Jones, Daniel A Drubach, David S Knopman, Bradley F Boeve, Nilüfer Ertekin-Taner, Ronald C Petersen, Val J Lowe, Clifford R Jack, Keith A Josephs
OBJECTIVE: To use a cluster analysis of [18 F]AV-1451 tau-PET data to determine how subjects with Alzheimer's disease vary in the relative involvement of the entorhinal cortex and neocortex, and determine whether relative involvement of these two regions can help explain variability in age and clinical phenotype in Alzheimer's disease. METHODS: We calculated [18 F]AV-1451 uptake in entorhinal cortex and neocortex in 62 amyloid-positive Alzheimer's disease patients (39 typical and 23 atypical presentation)...
January 11, 2018: Annals of Neurology
https://www.readbyqxmd.com/read/29315537/vitamin-transporters-in-mice-brain-with-aging
#12
P Marcos, J González-Fuentes, L Castro-Vázquez, M V Lozano, M J Santander-Ortega, V Rodríguez-Robledo, N Villaseca-González, M M Arroyo-Jiménez
Its high metabolic rate and high polyunsaturated fatty acid content make the brain very sensitive to oxidative damage. In the brain, neuronal metabolism occurs at a very high rate and generates considerable amounts of reactive oxygen species and free radicals, which accumulate inside neurons, leading to altered cellular homeostasis and integrity and eventually irreversible damage and cell death. A misbalance in redox metabolism and the subsequent neurodegeneration increase throughout the course of normal aging, leading to several age-related changes in learning and memory as well as motor functions...
January 8, 2018: Journal of Anatomy
https://www.readbyqxmd.com/read/29311746/hexadirectional-coding-of-visual-space-in-human-entorhinal-cortex
#13
Matthias Nau, Tobias Navarro Schröder, Jacob L S Bellmund, Christian F Doeller
Entorhinal grid cells map the local environment, but their involvement beyond spatial navigation remains elusive. We examined human functional MRI responses during a highly controlled visual tracking task and show that entorhinal cortex exhibited a sixfold rotationally symmetric signal encoding gaze direction. Our results provide evidence for a grid-like entorhinal code for visual space and suggest a more general role of the entorhinal grid system in coding information along continuous dimensions.
January 8, 2018: Nature Neuroscience
https://www.readbyqxmd.com/read/29311745/human-entorhinal-cortex-represents-visual-space-using-a-boundary-anchored-grid
#14
Joshua B Julian, Alexandra T Keinath, Giulia Frazzetta, Russell A Epstein
When participants performed a visual search task, functional MRI responses in entorhinal cortex exhibited a sixfold periodic modulation by gaze-movement direction. The orientation of this modulation was determined by the shape and orientation of the bounded search space. These results indicate that human entorhinal cortex represents visual space using a boundary-anchored grid, analogous to that used by rodents to represent navigable space.
January 8, 2018: Nature Neuroscience
https://www.readbyqxmd.com/read/29305438/asymmetric-tdp-pathology-in-primary-progressive-aphasia-with-right-hemisphere-language-dominance
#15
Garam Kim, Shahrooz Vahedi, Tamar Gefen, Sandra Weintraub, Eileen H Bigio, Marek-Marsel Mesulam, Changiz Geula
OBJECTIVE: To quantitatively examine the regional densities and hemispheric distribution of the 43-kDa transactive response DNA-binding protein (TDP-43) inclusions, neurons, and activated microglia in a left-handed patient with right hemisphere language dominance and logopenic-variant primary progressive aphasia (PPA). METHODS: Phosphorylated TDP-43 inclusions, neurons, and activated microglia were visualized with immunohistochemical and histologic methods. Markers were quantified bilaterally with unbiased stereology in language- and memory-related cortical regions...
January 5, 2018: Neurology
https://www.readbyqxmd.com/read/29290554/a-non-canonical-reticular-limbic-central-auditory-pathway-via-medial-septum-contributes-to-fear-conditioning
#16
Guang-Wei Zhang, Wen-Jian Sun, Brian Zingg, Li Shen, Jufang He, Ying Xiong, Huizhong W Tao, Li I Zhang
In the mammalian brain, auditory information is known to be processed along a central ascending pathway leading to auditory cortex (AC). Whether there exist any major pathways beyond this canonical auditory neuraxis remains unclear. In awake mice, we found that auditory responses in entorhinal cortex (EC) cannot be explained by a previously proposed relay from AC based on response properties. By combining anatomical tracing and optogenetic/pharmacological manipulations, we discovered that EC received auditory input primarily from the medial septum (MS), rather than AC...
December 21, 2017: Neuron
https://www.readbyqxmd.com/read/29288735/myelin-changes-at-the-early-stage-of-5xfad-mice
#17
Lihua Gu, Di Wu, Xiang Tang, Xinyang Qi, Xiaoli Li, Feng Bai, Xiaochun Chen, Qingguo Ren, Zhijun Zhang
Previous studies have demonstrated myelin deficits in Alzheimer's disease (AD). However, it is still unclear whether myelin deficits occur at early stage of AD. Our study aimed to investigate myelin deficits in 5XFAD mice dynamically in different cognition-associated brain regions at early stage of AD. Transmission electron microscopy (TEM) was applied to detect myelin changes in late-myelinating regions such as prelimbic area (PrL), retrosplenial granular cortex (Rsg), field CA1 of hippocampus (CA1) and entorhinal cortex (ERC) respectively at different stages (1, 2, 3 and 5 months of age) in 5XFAD mouse model...
December 27, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/29280734/interactions-between-stimulus-and-response-types-are-more-strongly-represented-in-the-entorhinal-cortex-than-in-its-upstream-regions-in-rats
#18
Eun-Hye Park, Jae-Rong Ahn, Inah Lee
Previously we reported results which suggested that response types are critical in dissociating the lateral entorhinal cortex (LEC) from the medial entorhinal cortex (MEC) in a scene memory task (Yoo and Lee, 2017). Here, we investigated whether the perirhinal cortex (PER) and postrhinal cortex (POR), the upstream regions of the LEC and MEC, respectively, could be dissociated similarly. We conducted four tasks by combining different stimulus and response types. Our results suggest that the PER is important whenever object recognition is required and, together with prior findings, imply that PER-LEC networks are essential in goal-directed interactions with objects...
December 27, 2017: ELife
https://www.readbyqxmd.com/read/29279308/conditional-deletion-of-hippocampal-ca2-ca3a-oxytocin-receptors-impairs-the-persistence-of-long-term-social-recognition-memory-in-mice
#19
Yu-Ting Lin, Tsan-Yu Hsieh, Tsung-Chih Tsai, Chien-Chung Chen, Chiung-Chun Huang, Kuei-Sen Hsu
Oxytocin (OXT) receptors (OXTRs) are prominently expressed in hippocampal CA2 and CA3 pyramidal neurons, but little is known about its physiological function. As the functional necessity of hippocampal CA2 for social memory processing, we tested whether CA2 OXTRs may contribute to long-term social recognition memory (SRM) formation. Here, we found that conditional deletion of Oxtr from forebrain (Oxtr-/-) or CA2/CA3a-restricted excitatory neurons in adult male mice impaired the persistence of long-term SRM but had no effect on sociability and preference for social novelty...
December 26, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29278888/healthy-versus-entorhinal-cortical-atrophy-identification-in-asymptomatic-apoe4-carriers-at-risk-for-alzheimer-s-disease
#20
Kyoko Konishi, Ridha Joober, Judes Poirier, Kathleen MacDonald, Mallar Chakravarty, Raihaan Patel, John Breitner, Véronique D Bohbot
Early detection of Alzheimer's disease (AD) has been challenging as current biomarkers are invasive and costly. Strong predictors of future AD diagnosis include lower volume of the hippocampus and entorhinal cortex, as well as the ɛ4 allele of the Apolipoprotein E gene (APOE) gene. Therefore, studying functions that are critically mediated by the hippocampus and entorhinal cortex, such as spatial memory, in APOE ɛ4 allele carriers, may be key to the identification of individuals at risk of AD, prior to the manifestation of cognitive impairments...
December 16, 2017: Journal of Alzheimer's Disease: JAD
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