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Frontiers in Cellular Neuroscience

Zsófia Hoyk, Melinda E Tóth, Nikolett Lénárt, Dóra Nagy, Brigitta Dukay, Alexandra Csefová, Ágnes Zvara, György Seprényi, András Kincses, Fruzsina R Walter, Szilvia Veszelka, Judit Vígh, Beáta Barabási, András Harazin, Ágnes Kittel, László G Puskás, Botond Penke, László Vígh, Mária A Deli, Miklós Sántha
Hypertriglyceridemia is not only a serious risk factor in the development of cardiovascular diseases, but it is linked to neurodegeneration, too. Previously, we generated transgenic mice overexpressing the human APOB-100 protein, a mouse model of human atherosclerosis. In this model we observed high plasma levels of triglycerides, oxidative stress, tau hyperphosphorylation, synaptic dysfunction, cognitive impairment, increased neural apoptosis and neurodegeneration. Neurovascular dysfunction is recognized as a key factor in the development of neurodegenerative diseases, but the cellular and molecular events linking cerebrovascular pathology and neurodegeneration are not fully understood...
2018: Frontiers in Cellular Neuroscience
Yoko Tominaga, Makiko Taketoshi, Takashi Tominaga
Activity-dependent changes in the input-output (I-O) relationship of a neural circuit are central in the learning and memory function of the brain. To understand circuit-wide adjustments, optical imaging techniques to probe the membrane potential at every component of neurons, such as dendrites, axons and somas, in the circuit are essential. We have been developing fast voltage-sensitive dye (VSD) imaging methods for quantitative measurements, especially for single-photon wide-field optical imaging. The long-term continuous measurements needed to evaluate circuit-wide modifications require stable and quantitative long-term recordings...
2018: Frontiers in Cellular Neuroscience
Yu-Chieh David Chen, Scarlet Jinhong Park, William W Ja, Anupama Dahanukar
In Drosophila , Pox-neuro ( Poxn ) is a member of the Paired box (Pax) gene family that encodes transcription factors with characteristic paired DNA-binding domains. During embryonic development, Poxn is expressed in sensory organ precursor (SOP) cells of poly-innervated external sensory (p-es) organs and is important for specifying p-es organ identity (chemosensory) as opposed to mono-innervated external sensory (m-es) organs (mechanosensory). In Poxn mutants, there is a transformation of chemosensory bristles into mechanosensory bristles...
2018: Frontiers in Cellular Neuroscience
Zoe J Looser, Matthew J P Barrett, Johannes Hirrlinger, Bruno Weber, Aiman S Saab
Myelination of axons by oligodendrocytes is a key feature of the remarkably fast operating CNS. Oligodendrocytes not only tune axonal conduction speed but are also suggested to maintain long-term axonal integrity by providing metabolic support to the axons they ensheath. However, how myelinating oligodendrocytes impact axonal energy homeostasis remains poorly understood and difficult to investigate. Here, we provide a method of how to study electrically active myelinated axons expressing genetically encoded sensors by combining electrophysiology and two-photon imaging of acutely isolated optic nerves...
2018: Frontiers in Cellular Neuroscience
Ana Bribian, Fernando Pérez-Cerdá, Carlos Matute, Laura López-Mascaraque
Multiple sclerosis (MS) is an autoimmune disease causing central nervous system (CNS) demyelination and axonal injury. In the last years the importance of astrocytes in MS is rapidly increasing, recognizing astrocytes as highly active players in MS pathogenesis. Usually the role assigned to astrocytes in MS lesions has been the formation of the glial scar, but now their implication during lesion formation and the immune response increasingly recognized. Since astrocytes are a heterogeneous cell population with diverse roles in the CNS, the aim of this study was to analyze the putative clonal response of astrocytes in a demyelinating scenario...
2018: Frontiers in Cellular Neuroscience
Chantelle Fourie, Yukti Vyas, Kevin Lee, Yewon Jung, Craig C Garner, Johanna M Montgomery
The SHANK family of synaptic proteins (SHANK1-3) are master regulators of the organizational structure of excitatory synapses in the brain. Mutations in SHANK1-3 are prevalent in patients with autism spectrum disorders (ASD), and loss of one copy of SHANK3 causes Phelan-McDermid Syndrome, a syndrome in which Autism occurs in >80% of cases. The synaptic stability of SHANK3 is highly regulated by zinc, driving the formation of postsynaptic protein complexes and increases in excitatory synaptic strength. As ASD-associated SHANK3 mutations retain responsiveness to zinc, here we investigated how increasing levels of dietary zinc could alter behavioral and synaptic deficits that occur with ASD...
2018: Frontiers in Cellular Neuroscience
Ruth Hornedo-Ortega, Ana B Cerezo, Rocío M de Pablos, Stéphanie Krisa, Tristan Richard, M Carmen García-Parrilla, Ana M Troncoso
Neuroinflammation is a pathological feature of quite a number of Central Nervous System diseases such as Alzheimer and Parkinson's disease among others. The hallmark of brain neuroinflammation is the activation of microglia, which are the immune resident cells in the brain and represents the first line of defense when injury or disease occur. Microglial activated cells can adopt different phenotypes to carry out its diverse functions. Thus, the shift into pro-inflammatory/neurotoxic or anti-inflammatory/neuroprotective phenotypes, depending of the brain environment, has totally changed the understanding of microglia in neurodegenerative disease...
2018: Frontiers in Cellular Neuroscience
Lu Yu, Yanhong Duan, Zheng Zhao, Wendi He, Ming Xia, Qiujuan Zhang, Xiaohua Cao
Hydroxysafflor yellow A (HSYA) is the major active chemical component of the safflower plant flower, which is widely used in Chinese medicine for cerebrovascular and cardiovascular disease treatment. Recent studies have demonstrated that HSYA exerts neuroprotective effect on cerebral ischemia, such as neuronal anti-apoptosis, antioxidant activity and oxygen free radical-scavenging. However, whether and how HSYA has a protective effect on cognitive impairment induced by cerebral ischemia reperfusion remains elusive...
2018: Frontiers in Cellular Neuroscience
Maia Datunashvili, Rahul Chaudhary, Mehrnoush Zobeiri, Annika Lüttjohann, Evanthia Mergia, Arnd Baumann, Sabine Balfanz, Björn Budde, Gilles van Luijtelaar, Hans-Christian Pape, Doris Koesling, Thomas Budde
The hyperpolarization-activated inward current, Ih , plays a key role in the generation of rhythmic activities in thalamocortical (TC) relay neurons. Cyclic nucleotides, like 3',5'-cyclic adenosine monophosphate (cAMP), facilitate voltage-dependent activation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels by shifting the activation curve of Ih to more positive values and thereby terminating the rhythmic burst activity. The role of 3',5'-cyclic guanosine monophosphate (cGMP) in modulation of Ih is not well understood...
2018: Frontiers in Cellular Neuroscience
Ming Yu, Li Guo, Nan Li, Kristin S Henzel, Huating Gu, Xiufang Ran, Wei Sun, Shuai Liu, Yingchang Lu, Dan Ehninger, Yu Zhou
BK channels are known regulators of neuronal excitability, synaptic plasticity, and memory. Our previous study showed that a paternal methyl donor-rich diet reduced the expression of Kcnmb2 , which encodes BK channel subunit beta 2, and caused memory deficits in offspring mice. To explore the underlying cellular mechanisms, we investigated the intrinsic and synaptic properties of CA1 pyramidal neurons of the F1 offspring mice whose fathers were fed with either a methyl donor-rich diet (MD) or regular control diet (CD) for 6 weeks before mating...
2018: Frontiers in Cellular Neuroscience
Jie Zhang, Caixia Wang, Haibo Shi, Danhong Wu, Weihai Ying
Cumulating evidence has indicated NAD+ deficiency as a common central pathological factor of multiple diseases and aging. NAD+ supplement is highly protective in various disease and aging models, while two key questions have remained unanswered: (1) Does extracellular NAD+ also produce its effects through its degradation product adenosine? (2) Does extracellular NAD+ produce the protective effects by affecting cells under pathological insults only, or by affecting both normal cell and the cells under pathological insults? Since extracellular NAD+ can be degraded into adenosine, and endogenous adenosine levels are in the nanomolar range under physiological conditions, extracellular NAD+ may produce its effects through its degradation into adenosine...
2018: Frontiers in Cellular Neuroscience
Yingzhu Chen, Liangzhu Wang, Lingling Zhang, Beilei Chen, Liu Yang, Xiaobo Li, Yuping Li, Hailong Yu
Connexin 43 (Cx43) widely exists in all components of the neurovascular unit (NVU) and is a constituent of gap junctions and hemichannels. In physiological states, gap junctions are open for regular intercellular communication, and the hemichannels present low open probability in astrocytes. After cerebral ischemia, a large number of hemichannels are unusually opened, leading to cell swelling and even death. Most known hemichannel blockers also inhibit gap junctions and sequentially obstruct normal electrical cell-cell communication...
2018: Frontiers in Cellular Neuroscience
Jing Wu, Sicong Peng, Linghui Xiao, Xiaoe Cheng, Haixia Kuang, Mengye Zhu, Daying Zhang, Changyu Jiang, Tao Liu
Spinal lamina II (substantia gelatinosa, SG) neurons integrate nociceptive information from the primary afferents and are classified according to electrophysiological (tonic firing, delayed firing, single spike, initial burst, phasic firing, gap firing and reluctant firing) or morphological (islet, central, vertical, radial and unclassified) criteria. T-type calcium (Cav3) channels play an essential role in the central mechanism of pathological pain, but the electrophysiological properties and the cell-type specific distribution of T-type channels in SG neurons have not been fully elucidated...
2018: Frontiers in Cellular Neuroscience
Yannick Nicolas Gerber, Guillaume Patrick Saint-Martin, Claire Mathilde Bringuier, Sylvain Bartolami, Christophe Goze-Bac, Harun Najib Noristani, Florence Evelyne Perrin
Spinal cord injury (SCI) induces a pronounced neuroinflammation driven by activation and proliferation of resident microglia as well as infiltrating peripheral monocyte-derived macrophages. Depending on the time post-lesion, positive and detrimental influences of microglia/macrophages on axonal regeneration had been reported after SCI, raising the issue whether their modulation may represent an attractive therapeutic strategy. Colony-stimulating factor 1 (CSF1) regulates microglia/macrophages proliferation, differentiation and survival thus, pharmacological treatments using CSF1 receptor (CSF1R) inhibitors had been used to ablate microglia...
2018: Frontiers in Cellular Neuroscience
Sandra M Cardona, Sangwon V Kim, Kaira A Church, Vanessa O Torres, Ian A Cleary, Andrew S Mendiola, Stephen P Saville, Stephanie S Watowich, Jan Parker-Thornburg, Alejandro Soto-Ospina, Pedronel Araque, Richard M Ransohoff, Astrid E Cardona
Multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS) is the leading cause of non-traumatic neurological disability in young adults. Immune mediated destruction of myelin and oligodendrocytes is considered the primary pathology of MS, but progressive axonal loss is the major cause of neurological disability. In an effort to understand microglia function during CNS inflammation, our laboratory focuses on the fractalkine/CX3CR1 signaling as a regulator of microglia neurotoxicity in various models of neurodegeneration...
2018: Frontiers in Cellular Neuroscience
Chao-Hua Huang, Tobias Moser
The early auditory pathway processes information at high rates and with utmost temporal fidelity. Consequently, the synapses in the auditory pathway are highly specialized to meet the extraordinary requirements on signal transmission. The calyceal synapses in the auditory brainstem feature more than a hundred active zones (AZs) with thousands of releasable synaptic vesicles (SVs). In contrast, the first auditory synapse, the afferent synapse of inner hair cells (IHCs) and type I spiral ganglion neurons (SGNs), typically exhibits a single ribbon-type AZ tethering only tens of SVs resulting in a highly stochastic pattern of transmitter release...
2018: Frontiers in Cellular Neuroscience
Saju Balakrishnan, Sergej L Mironov
Rett syndrome (RTT) is a neurological disorder caused by the mutation of the X-linked MECP2 gene. The neurophysiological hallmark of the RTT phenotype is the hyperexcitability of neurons made responsible for frequent epileptic attacks in the patients. Increased excitability in RTT might stem from impaired glutamate handling in RTT and its long-term consequences that has not been examined quantitatively. We recently reported (Balakrishnan and Mironov, 2018a,b) that the RTT hippocampus consistently demonstrates repetitive glutamate transients that parallel the burst firing in the CA1 neurons...
2018: Frontiers in Cellular Neuroscience
Monika Lakk, Derek Young, Jackson M Baumann, Andrew O Jo, Hongzhen Hu, David Križaj
Retinal ganglion cells (RGCs) are projection neurons that transmit the visual signal from the retina to the brain. Their excitability and survival can be strongly influenced by mechanical stressors, temperature, lipid metabolites, and inflammatory mediators but the transduction mechanisms for these non-synaptic sensory inputs are not well characterized. Here, we investigate the distribution, functional expression, and localization of two polymodal transducers of mechanical, lipid, and inflammatory signals, TRPV1 and TRPV4 cation channels, in mouse RGCs...
2018: Frontiers in Cellular Neuroscience
Gemma McGregor, Jenni Harvey
The role of the endocrine hormone leptin in controlling energy homeostasis in the hypothalamus are well documented. However the CNS targets for leptin are not restricted to the hypothalamus as a high density of leptin receptors are also expressed in several parts of the brain involved in higher cognitive functions including the hippocampus. Numerous studies have identified that in the hippocampus, leptin has cognitive enhancing actions as exogenous application of this hormone facilitates hippocampal-dependent learning and memory, whereas lack or insensitivity to leptin results in significant memory deficits...
2018: Frontiers in Cellular Neuroscience
Hongliu Sun, Luyu Ma, Yurong Zhang, Xiaohong Pan, Chaoyun Wang, Jinjin Zhang, Xiuli Zhang, Hongwei Sun, Qiaoyun Wang, Wei Zhu
Previous studies suggested that the thrombospondin-1/transforming growth factor-β1 (TSP-1/TGF-β1) pathway might be critical in synaptogenesis during development and that the purinergic P2 receptor family could regulate synaptogenesis by modulating TSP-1 signaling. However, it is unclear whether this pathway plays a role in synaptogenesis during epileptic progression. This study was designed to investigate this question by analyzing the dynamic changes and effects of TSP-1 levels on the density of synaptic markers that are related to epileptic seizure activity...
2018: Frontiers in Cellular Neuroscience
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