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https://www.readbyqxmd.com/read/28315269/sigma-1-receptors-and-neurodegenerative-diseases-towards-a-hypothesis-of-sigma-1-receptors-as-amplifiers-of-neurodegeneration-and-neuroprotection
#1
Linda Nguyen, Brandon P Lucke-Wold, Shona Mookerjee, Nidhi Kaushal, Rae R Matsumoto
Sigma-1 receptors are molecular chaperones that may act as pathological mediators and targets for novel therapeutic applications in neurodegenerative diseases. Accumulating evidence indicates that sigma-1 ligands can either directly or indirectly modulate multiple neurodegenerative processes, including excitotoxicity, calcium dysregulation, mitochondrial and endoplasmic reticulum dysfunction, inflammation, and astrogliosis. In addition, sigma-1 ligands may act as disease-modifying agents in the treatment for central nervous system (CNS) diseases by promoting the activity of neurotrophic factors and neural plasticity...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28262416/the-auxiliary-calcium-channel-subunit-%C3%AE-2%C3%AE-4-is-required-for-axonal-elaboration-synaptic-transmission-and-wiring-of-rod-photoreceptors
#2
Yuchen Wang, Katherine E Fehlhaber, Ignacio Sarria, Yan Cao, Norianne T Ingram, Debbie Guerrero-Given, Ben Throesch, Kristin Baldwin, Naomi Kamasawa, Toshihisa Ohtsuka, Alapakkam P Sampath, Kirill A Martemyanov
Neural circuit wiring relies on selective synapse formation whereby a presynaptic release apparatus is matched with its cognate postsynaptic machinery. At metabotropic synapses, the molecular mechanisms underlying this process are poorly understood. In the mammalian retina, rod photoreceptors form selective contacts with rod ON-bipolar cells by aligning the presynaptic voltage-gated Ca(2+) channel directing glutamate release (CaV1.4) with postsynaptic mGluR6 receptors. We show this coordination requires an extracellular protein, α2δ4, which complexes with CaV1...
March 22, 2017: Neuron
https://www.readbyqxmd.com/read/28243714/nicotine-withdrawal-induced-inattention-is-absent-in-alpha7-nachr-knockout-mice
#3
K K Higa, A Grim, M E Kamenski, J van Enkhuizen, X Zhou, K Li, J C Naviaux, L Wang, R K Naviaux, M A Geyer, A Markou, J W Young
RATIONALE: Smoking is the leading cause of preventable death in the USA, but quit attempts result in withdrawal-induced cognitive dysfunction and predicts relapse. Greater understanding of the neural mechanism(s) underlying these cognitive deficits is required to develop targeted treatments to aid quit attempts. OBJECTIVES: We examined nicotine withdrawal-induced inattention in mice lacking the α7 nicotinic acetylcholine receptor (nAChR) using the five-choice continuous performance test (5C-CPT)...
February 28, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28235660/targeting-the-tlr4-signaling-pathway-by-polyphenols-a-novel-therapeutic-strategy-for-neuroinflammation
#4
REVIEW
Mahban Rahimifard, Faheem Maqbool, Shermineh Moeini-Nodeh, Kamal Niaz, Mohammad Abdollahi, Nady Braidy, Seyed Mohammad Nabavi, Seyed Fazel Nabavi
A wide array of cell signaling mediators and their interactions play vital roles in neuroinflammation associated with ischemia, brain trauma, developmental disorders and age-related neurodegeneration. Along with neurons, microglia and astrocytes are also affected by the inflammatory cascade by releasing pro-inflammatory cytokines, chemokines and reactive oxygen species. The release of pro-inflammatory mediators in response to neural dysfunction may be helpful, neutral or even deleterious to normal cellular survival...
February 21, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28228252/complete-disruption-of-the-kainate-receptor-gene-family-results-in-corticostriatal-dysfunction-in-mice
#5
Jian Xu, John J Marshall, Herman B Fernandes, Toshihiro Nomura, Bryan A Copits, Daniele Procissi, Susumu Mori, Lei Wang, Yongling Zhu, Geoffrey T Swanson, Anis Contractor
Kainate receptors are members of the glutamate receptor family that regulate synaptic function in the brain. They modulate synaptic transmission and the excitability of neurons; however, their contributions to neural circuits that underlie behavior are unclear. To understand the net impact of kainate receptor signaling, we generated knockout mice in which all five kainate receptor subunits were ablated (5ko). These mice displayed compulsive and perseverative behaviors, including over-grooming, as well as motor problems, indicative of alterations in striatal circuits...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28212375/epilepsy-associated-gene-nedd4-2-mediates-neuronal-activity-and-seizure-susceptibility-through-ampa-receptors
#6
Jiuhe Zhu, Kwan Young Lee, Kathryn A Jewett, Heng-Ye Man, Hee Jung Chung, Nien-Pei Tsai
The neural precursor cell expressed developmentally down-regulated gene 4-2, Nedd4-2, is an epilepsy-associated gene with at least three missense mutations identified in epileptic patients. Nedd4-2 encodes a ubiquitin E3 ligase that has high affinity toward binding and ubiquitinating membrane proteins. It is currently unknown how Nedd4-2 mediates neuronal circuit activity and how its dysfunction leads to seizures or epilepsies. In this study, we provide evidence to show that Nedd4-2 mediates neuronal activity and seizure susceptibility through ubiquitination of GluA1 subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, (AMPAR)...
February 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28188216/amygdalar-gating-of-early-sensory-processing-through-interactions-with-locus-coeruleus
#7
Cynthia D Fast, John P McGann
Fear- and stress-induced activity in the amygdala has been hypothesized to influence sensory brain regions through the influence of the amygdala on neuromodulatory centers. To directly examine this relationship, we used optical imaging to observe odor-evoked activity in populations of olfactory bulb inhibitory interneurons and of synaptic terminals of olfactory sensory neurons (the primary sensory neurons of the olfactory system, which provide the initial olfactory input to the brain) during pharmacological inactivation of amygdala and locus coeruleus (LC) in mice...
March 15, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28177983/the-contribution-of-transgenic-and-nontransgenic-animal-models-in-alzheimer-s-disease-drug-research-and-development
#8
Emanuela Mhillaj, Vincenzo Cuomo, Cesare Mancuso
Over the last few years, several papers have become available in the literature on both the main hallmarks of Alzheimer's disease (AD) and the several intracellular pathways whose alteration is responsible for its onset and progression. The use of transgenic and nontransgenic animal models has played a key role in achieving such a remarkable amount of preclinical data, allowing researchers to dissect the cellular changes occurring in the AD brain. In addition, the huge amount of preclinical evidence arising from these animal models was necessary for the further clinical development of pharmacological agents capable of interfering with most of the impaired neural pathways in AD patients...
April 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28167808/how-do-individuals-cope-with-stress-behavioural-physiological-and-neuronal-differences-between-proactive-and-reactive-coping-styles-in-fish
#9
Marco A Vindas, Marnix Gorissen, Erik Höglund, Gert Flik, Valentina Tronci, Børge Damsgård, Per-Ove Thörnqvist, Tom O Nilsen, Svante Winberg, Øyvind Øverli, Lars O E Ebbesson
Despite the use of fish models to study human mental disorders and dysfunctions, knowledge of regional telencephalic responses in non-mammalian vertebrates expressing alternate stress coping styles is poor. Since perception of salient stimuli associated with stress coping in mammals is mainly under forebrain limbic control, we tested region-specific forebrain neural (i.e mRNA abundance and monoamine neurochemistry) and endocrine responses at basal and acute stress conditions for previously characterised proactive and reactive Atlantic salmon...
February 6, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28161362/ngf-dependent-axon-growth-and-regeneration-are-altered-in-sympathetic-neurons-of-dystrophic-mdx-mice
#10
Loredana Lombardi, Irene Persiconi, Alessandra Gallo, Casper C Hoogenraad, Maria Egle De Stefano
Duchenne muscular dystrophy (DMD) is a lethal disease, determined by lack of dystrophin (Dp427), a muscular cytoskeletal protein also expressed by selected neuronal populations. Consequently, besides muscular wasting, both human patients and DMD animal models suffer several neural disorders. In previous studies on the superior cervical ganglion (SCG) of wild type and dystrophic mdx mice (Lombardi et al. 2008), we hypothesized that Dp427 could play some role in NGF-dependent axonal growth, both during development and adulthood...
February 2, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28114835/dorsal-striatum-d1-expressing-neurons-are-involved-with-sensorimotor-gating-on-prepulse-inhibition-test
#11
Samanta Rodrigues, Cristiane Salum, Tatiana L Ferreira
Prepulse inhibition (PPI) is a behavioral test in which the startle reflex response to a high-intensity stimulus (pulse) is inhibited by the prior presentation of a weak stimulus (prepulse). The classic neural circuitry that mediates startle response is localized in the brainstem; however, recent studies point to the contribution of structures involved in higher cognitive functions in regulating the sensorimotor gating, particularly forebrain regions innervated by dopaminergic nuclei. The aim of the present study was to verify the role of dorsal striatum (DS) and dopaminergic transmitting mediated by D1 and D2 receptors on PPI test in rats...
January 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28114090/-pro-inflammatory-cytokines-in-alzheimer-s-disease
#12
E C Stamouli, A M Politis
Alzheimer's disease (AD), the most common progressive neurodegenerative disorder in the elderly, is clinically characterized by progressive impairment of cognitive functions, including reduced critical capacity, weakness of decision-making and problem orientation, while in the more advanced stages it is accompanied by behavioral disorders and impaired verbal ability. Neuropathological characteristics of the disease are the neurofibrillary tangles (NFT), the neuritic plaques (NP), the prominent synaptic loss and eventually the neuronal loss...
October 2016: Psychiatrikē, Psychiatriki
https://www.readbyqxmd.com/read/28074532/pathogenesis-of-developmental-anomalies-of-the-central-nervous-system-induced-by-congenital-cytomegalovirus-infection
#13
REVIEW
Hideya Kawasaki, Isao Kosugi, Shiori Meguro, Toshihide Iwashita
In humans, the herpes virus family member cytomegalovirus (CMV) is the most prevalent mediator of intrauterine infection-induced congenital defect. Central nervous system (CNS) dysfunction is a distinguishing symptom of CMV infection, and characterized by ventriculoencephalitis and microglial nodular encephalitis. Reports on the initial distribution of CMV particles and its receptors on the blood brain barrier (BBB) are rare. Nevertheless, several factors are suggested to affect CMV etiology. Viral particle size is the primary factor in determining the pattern of CNS infections, followed by the expression of integrin β1 in endothelial cells, pericytes, meninges, choroid plexus, and neural stem progenitor cells (NSPCs), which are the primary targets of CMV infection...
February 2017: Pathology International
https://www.readbyqxmd.com/read/27995932/intranasal-oxytocin-and-vasopressin-modulate-divergent-brainwide-functional-substrates
#14
Alberto Galbusera, Alessia De Felice, Stefano Girardi, Giacomo Bassetto, Marta Maschietto, Katsuhiko Nishimori, Bice Chini, Francesco Papaleo, Stefano Vassanelli, Alessandro Gozzi
The neuropeptides oxytocin (OXT) and vasopressin (AVP) have been identified as modulators of emotional social behaviors and associated with neuropsychiatric disorders characterized by social dysfunction. Experimental and therapeutic use of OXT and AVP via the intranasal route is the subject of extensive clinical research. However, the large-scale functional substrates directly engaged by these peptides and their functional dynamics remain elusive. By using cerebral blood volume (CBV) weighted fMRI in the mouse, we show that intranasal administration of OXT rapidly elicits the transient activation of cortical regions and a sustained activation of hippocampal and forebrain areas characterized by high oxytocin receptor density...
January 18, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27975174/dysregulation-of-intracellular-ca-2-in-dystrophic-cortical-and-hippocampal-neurons
#15
José R Lopez, Juan Kolster, Arkady Uryash, Eric Estève, Francisco Altamirano, José A Adams
Duchenne muscular dystrophy (DMD) is an inherited X-linked disorder characterized by skeletal muscle wasting, cardiomyopathy, as well as cognitive impairment. Lack of dystrophin in striated muscle produces dyshomeostasis of resting intracellular Ca(2+) ([Ca(2+)]i), Na(+) ([Na(+)]i), and oxidative stress. Here, we test the hypothesis that similar to striated muscle cells, an absence of dystrophin in neurons from mdx mice (a mouse model for DMD) is also associated with dysfunction of [Ca(2+)]i homeostasis and oxidative stress...
December 15, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27955702/%C3%AE-amyloid-triggers-aberrant-over-scaling-of-homeostatic-synaptic-plasticity
#16
James Gilbert, Shu Shu, Xin Yang, Youming Lu, Ling-Qiang Zhu, Heng-Ye Man
The over-production of β-amyloid (Aβ) has been strongly correlated to neuronal dysfunction and altered synaptic plasticity in Alzheimer's disease (AD). Accordingly, it has been proposed that disrupted synaptic transmission and neuronal network instability underlie memory failure that is evident in the early phases of AD. Homeostatic synaptic plasticity (HSP) serves to restrain neuronal activity within a physiological range. Therefore a disruption of this mechanism may lead to destabilization in synaptic and neural circuit function...
December 13, 2016: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/27932955/what-do-we-really-know-about-5-ht1a-receptor-signaling-in-neuronal-cells
#17
REVIEW
Paulina S Rojas, Jenny L Fiedler
Serotonin (5-HT) is a neurotransmitter that plays an important role in neuronal plasticity. Variations in the levels of 5-HT at the synaptic cleft, expression or dysfunction of 5-HT receptors may alter brain development and predispose to various mental diseases. Here, we review the transduction pathways described in various cell types transfected with recombinant 5-HT1A receptor (5-HT1AR), specially contrasting with those findings obtained in neuronal cells. The 5-HT1AR is detected in early stages of neural development and is located in the soma, dendrites and spines of hippocampal neurons...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27926574/neural-activity-memory-and-dementias-serotonergic-markers
#18
Alfredo Meneses
Dysfunctional memory seems to be a key component of diverse dementias and other neuropsychiatric disorders; unfortunately, no effective treatment exists for this, probably because of the absence of neural biomarkers accompanying it. Diverse neurotransmission systems have been implicated in memory, including serotonin or 5-hydroxytryptamine (5-HT). There are multiple serotonergic pharmacological tools, well-characterized downstream signaling in mammals' species and neural markers providing new insights into memory functions and dysfunctions...
April 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/27913408/neurophysiological-mechanisms-of-cortical-plasticity-impairments-in-schizophrenia-and-modulation-by-the-nmda-receptor-agonist-d-serine
#19
Joshua T Kantrowitz, Michael L Epstein, Odeta Beggel, Stephanie Rohrig, Jonathan M Lehrfeld, Nadine Revheim, Nayla P Lehrfeld, Jacob Reep, Emily Parker, Gail Silipo, Merav Ahissar, Daniel C Javitt
Schizophrenia is associated with deficits in cortical plasticity that affect sensory brain regions and lead to impaired cognitive performance. Here we examined underlying neural mechanisms of auditory plasticity deficits using combined behavioural and neurophysiological assessment, along with neuropharmacological manipulation targeted at the N-methyl-D-aspartate type glutamate receptor (NMDAR). Cortical plasticity was assessed in a cohort of 40 schizophrenia/schizoaffective patients relative to 42 healthy control subjects using a fixed reference tone auditory plasticity task...
December 2016: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/27906690/the-long-road-to-leptin
#20
Jeffrey Friedman
Leptin is an adipose tissue hormone that functions as an afferent signal in a negative feedback loop that maintains homeostatic control of adipose tissue mass. This endocrine system thus serves a critical evolutionary function by protecting individuals from the risks associated with being too thin (starvation) or too obese (predation and temperature dysregulation). Mutations in leptin or its receptor cause massive obesity in mice and humans, and leptin can effectively treat obesity in leptin-deficient patients...
December 1, 2016: Journal of Clinical Investigation
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