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  1. Article: Novel Targets of SARS-CoV-2 Spike Protein in Human Fetal Brain Development Suggest Early Pregnancy Vulnerability.

    Varma, Parul / Lybrand, Zane R / Antopia, Mariah C / Hsieh, Jenny

    Frontiers in neuroscience

    2021  Volume 14, Page(s) 614680

    Abstract: Pregnant women are at greater risk of infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), because of their altered immunity and strained cardiovascular system. Emerging studies of placenta, embryos, and cerebral organoids suggest ... ...

    Abstract Pregnant women are at greater risk of infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), because of their altered immunity and strained cardiovascular system. Emerging studies of placenta, embryos, and cerebral organoids suggest that fetal organs including brain could also be vulnerable to coronavirus disease 2019 (COVID-19). Additionally, a case study from Paris has reported transient neurological complications in neonates born to pregnant mothers. However, it remains poorly understood whether the fetal brain expresses cellular components that interact with Spike protein (S) of coronaviruses, which facilitates fusion of virus and host cell membrane and is the primary protein in viral entry. To address this question, we analyzed the expression of known (
    Language English
    Publishing date 2021-01-21
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2411902-7
    ISSN 1662-453X ; 1662-4548
    ISSN (online) 1662-453X
    ISSN 1662-4548
    DOI 10.3389/fnins.2020.614680
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  2. Article: Dual effects of

    Nieto-Estevez, Vanesa / Varma, Parul / Mirsadeghi, Sara / Caballero, Jimena / Gamero-Alameda, Sergio / Hosseini, Ali / Goswami, Sonal / Silvosa, Marc J / Thodeson, Drew M / Lybrand, Zane R / Giugliano, Michele / Navara, Christopher / Hsieh, Jenny

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Mutations ... ...

    Abstract Mutations in
    Language English
    Publishing date 2024-01-25
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.01.25.577271
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Stem cells: A path towards improved epilepsy therapies.

    Lybrand, Zane R / Goswami, Sonal / Hsieh, Jenny

    Neuropharmacology

    2019  Volume 168, Page(s) 107781

    Abstract: Despite the immense growth of new anti-seizure drugs (ASDs), approximately one-third of epilepsy patients remain resistant to current treatment options. Advancements in whole genome sequencing technology continues to identify an increasing number of ... ...

    Abstract Despite the immense growth of new anti-seizure drugs (ASDs), approximately one-third of epilepsy patients remain resistant to current treatment options. Advancements in whole genome sequencing technology continues to identify an increasing number of epilepsy-associated genes at a rate that is outpacing the development of in vivo animal models. Patient-derived induced pluripotent stem cells (iPSCs) show promise in providing a platform for modeling genetic epilepsies, high throughput drug screening, and personalized medicine. This is largely due to the ease of collecting donor cells for iPSC reprogramming, and their ability to be maintained in vitro, while preserving the patient's genetic background. In this review, we summarize the current state of iPSC research in epilepsy and closely related syndromes, discuss the growing need for high-throughput drug screening (HTS), and review the use of stem cell technology for the purpose of autologous transplantation for epilepsy stem cell therapy. Although the use of iPSC technology, as it applies to ASD discovery, is in its infancy, we highlight the significant progress that has been made in phenotype and assay development to facilitate systematic HTS for personalized medicine. This article is part of the special issue entitled 'New Epilepsy Therapies for the 21st Century - From Antiseizure Drugs to Prevention, Modification and Cure of Epilepsy'.
    MeSH term(s) Animals ; Anticonvulsants/administration & dosage ; Drug Discovery/methods ; Drug Discovery/trends ; Epilepsy/diagnosis ; Epilepsy/genetics ; Epilepsy/therapy ; Humans ; Induced Pluripotent Stem Cells/physiology ; Induced Pluripotent Stem Cells/transplantation ; Precision Medicine/methods ; Precision Medicine/trends ; Stem Cell Transplantation/methods ; Stem Cell Transplantation/trends
    Chemical Substances Anticonvulsants
    Language English
    Publishing date 2019-09-17
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 218272-5
    ISSN 1873-7064 ; 0028-3908
    ISSN (online) 1873-7064
    ISSN 0028-3908
    DOI 10.1016/j.neuropharm.2019.107781
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    In stock of ZB MED Cologne/Königswinter

    Ui I Zs.242: Show issues Location:
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    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: Understanding Primary Blast Injury: High Frequency Pressure Acutely Disrupts Neuronal Network Dynamics in Cerebral Organoids.

    Silvosa, Marc Joshua / Mercado, Nohemi Romo / Merlock, Nikolas / Vidhate, Suhas / Mejia-Alvarez, Ricardo / Yuan, Tony T / Willis, Adam M / Lybrand, Zane R

    Journal of neurotrauma

    2022  Volume 39, Issue 21-22, Page(s) 1575–1590

    Abstract: Blast exposure represents a common occupational risk capable of generating mild to severe traumatic brain injuries (TBI). During blast exposure, a pressure shockwave passes through the skull and exposes brain tissue to complex pressure waveforms. The ... ...

    Abstract Blast exposure represents a common occupational risk capable of generating mild to severe traumatic brain injuries (TBI). During blast exposure, a pressure shockwave passes through the skull and exposes brain tissue to complex pressure waveforms. The primary neurophysiological response to blast-induced pressure waveforms remains poorly understood. Here, we use a computer-controlled table-top pressure chamber to expose human stem cell-derived cerebral organoids to varied frequency of pressure waves and characterize the neurophysiological response. Pressure waves that reach a maximum amplitude of 250 kPa were used to model a less severe TBI and 350 kPa for a more severe blast TBI event. With each amplitude, a frequency range of 500 Hz, 3000 Hz, and 5000 Hz was tested. Following the 250 kPa overpressure a multi-electrode array recorded organoid neural activity. We observed an acute suppression neuronal activity in single unit events, population events, and network oscillations that recovered within 24 h. Additionally, we observed a network desynchronization after exposure higher frequency waveforms. Conversely, organoids exposed to higher amplitude pressure (350k Pa) displayed drastic neurophysiological differences that failed to recover within 24 h. Further, lower amplitude "blast" (250 kPa) did not induce cellular damage whereas the higher amplitude "blast" (350 kPa) generated greater apoptosis throughout each organoid. Our data indicate that specific features of pressure waves found intracranially during blast TBI have varied effects on neurophysiological activity that can occur even without cellular damage.
    MeSH term(s) Humans ; Blast Injuries ; Organoids ; Explosions ; Neurons/physiology ; Brain Injuries, Traumatic
    Language English
    Publishing date 2022-07-11
    Publishing country United States
    Document type Journal Article
    ZDB-ID 645092-1
    ISSN 1557-9042 ; 0897-7151
    ISSN (online) 1557-9042
    ISSN 0897-7151
    DOI 10.1089/neu.2022.0044
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2016: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
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  5. Article ; Online: Coupled sensory interneurons mediate escape neural circuit processing in an aquatic annelid worm, Lumbriculus variegatus.

    Lybrand, Zane R / Martinez-Acosta, Veronica G / Zoran, Mark J

    The Journal of comparative neurology

    2019  Volume 528, Issue 3, Page(s) 468–480

    Abstract: The interneurons associated with rapid escape circuits are adapted for fast pathway activation and rapid conduction. An essential aspect of fast activation is the processing of sensory information with limited delays. Although aquatic annelid worms have ... ...

    Abstract The interneurons associated with rapid escape circuits are adapted for fast pathway activation and rapid conduction. An essential aspect of fast activation is the processing of sensory information with limited delays. Although aquatic annelid worms have some of the fastest escape responses in nature, the sensory networks that mediate their escape behavior are not well defined. Here, we demonstrate that the escape circuit of the mud worm, Lumbriculus variegatus, is a segmentally arranged network of sensory interneurons electrically coupled to the central medial giant fiber (MGF), the command-like interneuron for head withdrawal. Electrical stimulation of the body wall evoked fast, short-duration spikelets in the MGF, which we suggest are the product of intermediate giant fiber activation coupled to MGF collateral dendrites. Since these contact sites have immunoreactivity with a glutamate receptor antibody, and the glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dion abolishes evoked MGF responses, we conclude that the afferent pathway for MGF-mediated escape is glutamatergic. This electrically coupled sensory network may facilitate rapid escape activation by enhancing the amplitude of giant axon depolarization.
    MeSH term(s) Animals ; Annelida ; Excitatory Amino Acid Antagonists/pharmacology ; Excitatory Postsynaptic Potentials/drug effects ; Excitatory Postsynaptic Potentials/physiology ; Interneurons/drug effects ; Interneurons/physiology ; Interneurons/ultrastructure ; Nerve Net/drug effects ; Nerve Net/physiology ; Nerve Net/ultrastructure ; Oligochaeta ; Sensory Receptor Cells/drug effects ; Sensory Receptor Cells/physiology ; Sensory Receptor Cells/ultrastructure
    Chemical Substances Excitatory Amino Acid Antagonists
    Language English
    Publishing date 2019-10-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3086-7
    ISSN 1096-9861 ; 0021-9967 ; 0092-7317
    ISSN (online) 1096-9861
    ISSN 0021-9967 ; 0092-7317
    DOI 10.1002/cne.24769
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    In stock of ZB MED Cologne/Königswinter

    Ub I Zs.66: Show issues Location:
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  6. Article ; Online: Rapid neural circuit switching mediated by synaptic plasticity during neural morphallactic regeneration.

    Lybrand, Zane R / Zoran, Mark J

    Developmental neurobiology

    2012  Volume 72, Issue 9, Page(s) 1256–1266

    Abstract: The aquatic oligochaete, Lumbriculus variegatus (Lumbriculidae), undergoes a rapid regenerative transformation of its neural circuits following body fragmentation. This type of nervous system plasticity, called neural morphallaxis, involves the ... ...

    Abstract The aquatic oligochaete, Lumbriculus variegatus (Lumbriculidae), undergoes a rapid regenerative transformation of its neural circuits following body fragmentation. This type of nervous system plasticity, called neural morphallaxis, involves the remodeling of the giant fiber pathways that mediate rapid head and tail withdrawal behaviors. Extra- and intracellular electrophysiological recordings demonstrated that changes in cellular properties and synaptic connections underlie neurobehavioral plasticity during morphallaxis. Sensory-to-giant interneuron connections, undetectable prior to body injury, emerged within hours of segment amputation. The appearance of functional synaptic transmission was followed by interneuron activation, coupling of giant fiber spiking to motor outputs and overt segmental shortening. The onset of morphallactic plasticity varied along the body axis and emerged more rapidly in segments closer to regions of sensory field overlap between the two giant fiber pathways. The medial and lateral giant fibers were simultaneously activated during a transient phase of network remodeling. Thus, synaptic plasticity at sensory-to-giant interneuron connections mediates escape circuit morphallaxis in this regenerating annelid worm.
    MeSH term(s) Animals ; Axons/physiology ; Axons/ultrastructure ; Nerve Regeneration/physiology ; Nervous System Physiological Phenomena/physiology ; Neural Pathways/cytology ; Neural Pathways/growth & development ; Neuronal Plasticity/physiology ; Oligochaeta/cytology ; Oligochaeta/growth & development ; Reaction Time/physiology ; Sensory Receptor Cells/cytology ; Sensory Receptor Cells/physiology ; Synapses/physiology ; Synapses/ultrastructure ; Time Factors
    Language English
    Publishing date 2012-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2256184-5
    ISSN 1932-846X ; 1097-4695 ; 1932-8451 ; 0022-3034
    ISSN (online) 1932-846X ; 1097-4695
    ISSN 1932-8451 ; 0022-3034
    DOI 10.1002/dneu.20993
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 853: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
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  7. Article ; Online: A critical period of neuronal activity results in aberrant neurogenesis rewiring hippocampal circuitry in a mouse model of epilepsy.

    Lybrand, Zane R / Goswami, Sonal / Zhu, Jingfei / Jarzabek, Veronica / Merlock, Nikolas / Aktar, Mahafuza / Smith, Courtney / Zhang, Ling / Varma, Parul / Cho, Kyung-Ok / Ge, Shaoyu / Hsieh, Jenny

    Nature communications

    2021  Volume 12, Issue 1, Page(s) 1423

    Abstract: In the mammalian hippocampus, adult-born granule cells (abGCs) contribute to the function of the dentate gyrus (DG). Disruption of the DG circuitry causes spontaneous recurrent seizures (SRS), which can lead to epilepsy. Although abGCs contribute to ... ...

    Abstract In the mammalian hippocampus, adult-born granule cells (abGCs) contribute to the function of the dentate gyrus (DG). Disruption of the DG circuitry causes spontaneous recurrent seizures (SRS), which can lead to epilepsy. Although abGCs contribute to local inhibitory feedback circuitry, whether they are involved in epileptogenesis remains elusive. Here, we identify a critical window of activity associated with the aberrant maturation of abGCs characterized by abnormal dendrite morphology, ectopic migration, and SRS. Importantly, in a mouse model of temporal lobe epilepsy, silencing aberrant abGCs during this critical period reduces abnormal dendrite morphology, cell migration, and SRS. Using mono-synaptic tracers, we show silencing aberrant abGCs decreases recurrent CA3 back-projections and restores proper cortical connections to the hippocampus. Furthermore, we show that GABA-mediated amplification of intracellular calcium regulates the early critical period of activity. Our results demonstrate that aberrant neurogenesis rewires hippocampal circuitry aggravating epilepsy in mice.
    MeSH term(s) Animals ; Calcium/metabolism ; Clozapine/analogs & derivatives ; Clozapine/pharmacology ; Disease Models, Animal ; Electroencephalography ; Epilepsy/physiopathology ; Epilepsy, Temporal Lobe/physiopathology ; Female ; Hippocampus/physiopathology ; Mice, Inbred C57BL ; Mice, Transgenic ; Neurogenesis/drug effects ; Neurogenesis/physiology ; Neurons/drug effects ; Neurons/metabolism ; Neurons/pathology ; Pilocarpine/pharmacology ; Retroviridae/genetics ; Seizures/physiopathology ; gamma-Aminobutyric Acid/metabolism ; Mice
    Chemical Substances Pilocarpine (01MI4Q9DI3) ; gamma-Aminobutyric Acid (56-12-2) ; Clozapine (J60AR2IKIC) ; clozapine N-oxide (MZA8BK588J) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2021-03-03
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Video-Audio Media
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-021-21649-8
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  8. Article ; Online: Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline.

    Cho, Kyung-Ok / Lybrand, Zane R / Ito, Naoki / Brulet, Rebecca / Tafacory, Farrah / Zhang, Ling / Good, Levi / Ure, Kerstin / Kernie, Steven G / Birnbaum, Shari G / Scharfman, Helen E / Eisch, Amelia J / Hsieh, Jenny

    Nature communications

    2015  Volume 6, Page(s) 6606

    Abstract: Acute seizures after a severe brain insult can often lead to epilepsy and cognitive impairment. Aberrant hippocampal neurogenesis follows the insult but the role of adult-generated neurons in the development of chronic seizures or associated cognitive ... ...

    Abstract Acute seizures after a severe brain insult can often lead to epilepsy and cognitive impairment. Aberrant hippocampal neurogenesis follows the insult but the role of adult-generated neurons in the development of chronic seizures or associated cognitive deficits remains to be determined. Here we show that the ablation of adult neurogenesis before pilocarpine-induced acute seizures in mice leads to a reduction in chronic seizure frequency. We also show that ablation of neurogenesis normalizes epilepsy-associated cognitive deficits. Remarkably, the effect of ablating adult neurogenesis before acute seizures is long lasting as it suppresses chronic seizure frequency for nearly 1 year. These findings establish a key role of neurogenesis in chronic seizure development and associated memory impairment and suggest that targeting aberrant hippocampal neurogenesis may reduce recurrent seizures and restore cognitive function following a pro-epileptic brain insult.
    MeSH term(s) Animals ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Cognition Disorders/chemically induced ; Cognition Disorders/etiology ; Cognition Disorders/physiopathology ; Disease Models, Animal ; Epilepsy/chemically induced ; Epilepsy/complications ; Epilepsy/physiopathology ; Epilepsy, Temporal Lobe/chemically induced ; Epilepsy, Temporal Lobe/complications ; Epilepsy, Temporal Lobe/physiopathology ; Hippocampus/growth & development ; Hippocampus/metabolism ; Hippocampus/physiopathology ; Immunohistochemistry ; Mice ; Mice, Transgenic ; Microtubule-Associated Proteins/metabolism ; Muscarinic Agonists/toxicity ; Nerve Tissue Proteins/metabolism ; Neural Stem Cells ; Neurogenesis/genetics ; Neurogenesis/physiology ; Neurons/metabolism ; Neuropeptides/metabolism ; Pilocarpine/toxicity
    Chemical Substances Basic Helix-Loop-Helix Transcription Factors ; Microtubule-Associated Proteins ; Muscarinic Agonists ; Nerve Tissue Proteins ; Neuropeptides ; doublecortin protein ; Pilocarpine (01MI4Q9DI3) ; Neurogenic differentiation factor 1 (169238-82-8)
    Language English
    Publishing date 2015-03-26
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/ncomms7606
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