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doxycycline and memory

Roopashri Holehonnur, Aarron J Phensy, Lily J Kim, Milica Milivojevic, Dat Vuong, Delvin K Daison, Saira Alex, Michael Tiner, Lauren E Jones, Sven Kroener, Jonathan E Ploski
UNLABELLED: Reconsolidation updating is a form of memory modification in which an existing memory can become destabilized upon retrieval and subsequently be modified via protein-synthesis-dependent reconsolidation. However, not all memories appear to destabilize upon retrieval and thus are not modifiable via reconsolidation updating approaches and the neurobiological basis for this remains poorly understood. Here, we report that auditory fear memories created with 10 tone-shock pairings are resistant to retrieval-dependent memory destabilization and are associated with an increase in the synaptic GluN2A/GluN2B ratio in neurons of the basal and lateral amygdala (BLA) compared with weaker fear memories created via one or three tone-shock pairings...
September 7, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
James P Kesby, Athina Markou, Svetlana Semenova
Depression and psychostimulant abuse are common comorbidities among humans with immunodeficiency virus (HIV) disease. The HIV regulatory protein TAT is one of multiple HIV-related proteins associated with HIV-induced neurotoxicity. TAT-induced dysfunction of dopamine and serotonin systems in corticolimbic brain areas may result in impaired reward function, thus, contributing to depressive symptoms and psychostimulant abuse. Transgenic mice with doxycycline-induced TAT protein expression in the brain (TAT+, TAT- control) show neuropathology resembling brain abnormalities in HIV+ humans...
October 2016: Neuropharmacology
Nikolay Martyushenko, Sigurd Hagen Johansen, Cheol-Min Ghim, Eivind Almaas
BACKGROUND: Genetic switches are ubiquitous in nature, frequently associated with the control of cellular functions and developmental programs. In the realm of synthetic biology, it is of great interest to engineer genetic circuits that can change their mode of operation from monostable to bistable, or even to multistable, based on the experimental fine-tuning of readily accessible parameters. In order to successfully design robust, bistable synthetic circuits to be used as biomolecular probes, or understand modes of operation of such naturally occurring circuits, we must identify parameters that are key in determining their characteristics...
2016: BMC Systems Biology
James P Kesby, Athina Markou, Svetlana Semenova
Neurotoxic viral protein TAT may contribute to deficits in dopaminergic and cognitive function in individuals infected with human immunodeficiency virus. Transgenic mice with brain-specific doxycycline-induced TAT expression (TAT+, TAT- control) show impaired cognition. However, previously reported TAT-induced deficits in reversal learning may be compromised by initial learning deficits. We investigated the effects of TAT expression on memory retention/recall and reversal learning, and neurotransmitter function...
September 15, 2016: Behavioural Brain Research
Anna G McNally, Shane G Poplawski, Brittany A Mayweather, Kyle M White, Ted Abel
The consolidation of short-term labile memories for long-term storage requires transcription and there is growing interest in defining the epigenetic mechanisms regulating these transcriptional events. In particular, it has been hypothesized that combinations of histone post-translational modifications (PTMs) have the potential to store memory by dynamically defining the transcriptional status of any given gene loci. Studying epigenetic phenomena during long-term memory consolidation, however, is complicated by the complex cellular heterogeneity of the brain, in which epigenetic signal from memory-relevant cells can be obscured or diluted by the surrounding milieu...
2016: Frontiers in Molecular Neuroscience
Guillaume Martel, Shusaku Uchida, Charles Hevi, Itzamarie Chévere-Torres, Ileana Fuentes, Young Jin Park, Hannah Hafeez, Hirotaka Yamagata, Yoshifumi Watanabe, Gleb P Shumyatsky
UNLABELLED: Neurogenesis and memory formation are essential features of the dentate gyrus (DG) area of the hippocampus, but to what extent the mechanisms responsible for both processes overlap remains poorly understood. Stathmin protein, whose tubulin-binding and microtubule-destabilizing activity is negatively regulated by its phosphorylation, is prominently expressed in the DG. We show here that stathmin is involved in neurogenesis, spinogenesis, and memory formation in the DG. tTA/tetO-regulated bitransgenic mice, expressing the unphosphorylatable constitutively active Stathmin4A mutant (Stat4A), exhibit impaired adult hippocampal neurogenesis and reduced spine density in the DG granule neurons...
January 27, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Alejandro S Cazzulino, Randy Martinez, Nicole K Tomm, Christine A Denny
Recent studies have focused on the identification and manipulation of memory traces in rodent models. The two main mouse models utilized are either a CreER(T2) /loxP tamoxifen (TAM)- or a tetracycline transactivator/tetracycline-response element doxycycline-inducible system. These systems, however, could be improved to label a more specific population of activated neurons corresponding to behavior. Here, we sought to identify an improved selective estrogen receptor (ER) modulator (SERM) in which we could label an individual memory trace in ArcCreER(T2) mice...
June 2016: Hippocampus
Hannah M Jahn, Anja Scheller, Frank Kirchhoff
During the last two decades numerous genetic approaches affecting cell function in vivo have been developed. Current state-of-the-art technology permits the selective switching of gene function in distinct cell populations within the complex organization of a given tissue parenchyma. The tamoxifen-inducible Cre/loxP gene recombination and the doxycycline-dependent modulation of gene expression are probably the most popular genetic paradigms. Here, we will review applications of these two strategies while focusing on the interactions of astrocytes and neurons in the central nervous system (CNS) and their impact for the whole organism...
2015: Frontiers in Cellular Neuroscience
Abdul Hannan, Alia Batool, Muhammad Usman Qamar, Fizza Khalid
BACKGROUND: Multidrug resistant (MDR) Acinetobacter baumannii has emerged as an important health care problem. The organism is now identified as an important nosocomial pathogen particularly in the intensive care settings. The therapeutic options to treat this pathogen are limited; thus it needs testing for alternatives, like those of plant origin or natural products. Propolis is one of such products which have been tested against this organism. METHODS: A. baumannii (n=32) were collected from Fatima Memorial Hospital, Lahore...
January 2015: Journal of Ayub Medical College, Abbottabad: JAMC
Emily M Laswell, Kasandra D Chambers, Danielle R Whitsel, Kiran Poudel
New-onset refractory status epilepticus (NORSE) is defined as a sudden onset of refractory status epilepticus in patients who do not have a history of epilepsy. It is a neurologic emergency, and determining the underlying etiology is an important factor for effectively managing and predicting the prognosis of NORSE. We describe the case of a 28-year-old woman who was hospitalized with NORSE secondary to an unknown etiology. She did not respond to traditional anticonvulsant therapy, including benzodiazepines, fosphenytoin, propofol, and levetiracetam...
June 2015: Pharmacotherapy
Panta Rouhani Schaffer, Christopher S Hale, Shane A Meehan, Jerome L Shupack, Sarika Ramachandran
We report a 46-year-old woman with a nine-year history of obesity; chronic diffuse pain in the adipose tissue of her medial upper arms, lower trunk, and thighs; multiple biopsy-proven lipomas and angiolipomas; and a lipomatous pseudomass of the breast. Her systemic symptoms included generalized weakness, fatigue, memory impairment, and arthralgias. Although some of the lesions were tender, most were only appreciated with palpation. Her clinical history and histopathologic data suggested adiposis dolorosa (Dercum's disease)...
December 2014: Dermatology Online Journal
Julio A Alfieri, Natalia S Pino, Lionel M Igaz
Transactive response DNA-binding protein 43 (TDP-43) mislocalization and aggregation are hallmark features of amyotrophic lateral sclerosis and frontotemporal dementia (FTD). We have previously shown in mice that inducible overexpression of a cytoplasmically localized form of TDP-43 (TDP-43-ΔNLS) in forebrain neurons evokes neuropathological changes that recapitulate several features of TDP-43 proteinopathies. Detailed behavioral phenotyping could provide further validation for its usage as a model for FTD...
November 12, 2014: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Teske Schoffelen, Alfons A den Broeder, Marrigje Nabuurs-Franssen, Marcel van Deuren, Tom Sprong
BACKGROUND: Q fever is caused by the intracellular bacterium Coxiella burnetii. Initial infection can present as acute Q fever, while a minority of infected individuals develops chronic Q fever endocarditis or vascular infection months to years after initial infection. Serology is an important diagnostic tool for both acute and chronic Q fever. However, since immunosuppressive drugs may hamper the humoral immune response, diagnosis of Q fever might be blurred when these drugs are used...
2014: BMC Infectious Diseases
Yingbo He, Hui Zhang, Andrea Yung, Saul A Villeda, Philipp A Jaeger, Oluwatobi Olayiwola, Nina Fainberg, Tony Wyss-Coray
The transforming growth factor-β (TGF-β) signaling pathway serves critical functions in CNS development, but, apart from its proposed neuroprotective actions, its physiological role in the adult brain is unclear. We observed a prominent activation of TGF-β signaling in the adult dentate gyrus and expression of downstream Smad proteins in this neurogenic zone. Consistent with a function of TGF-β signaling in adult neurogenesis, genetic deletion of the TGF-β receptor ALK5 reduced the number, migration and dendritic arborization of newborn neurons...
July 2014: Nature Neuroscience
Norio Wada, Kazuo Funabiki, Shigetada Nakanishi
Adaptation of the optokinetic response (OKR) is an eye movement enhanced by repeated motion of a surrounding visual field and represents a prototype of cerebellum-dependent motor learning. Purkinje cells and vestibular nuclei (VN) receive optokinetic and retinal slip signals via the mossy fiber-granule cell pathway and climbing-fiber projections, respectively. To explore the neural circuits and mechanisms responsible for OKR adaptation, we adopted the reversible neurotransmission-blocking (RNB) technique, in which granule-cell transmission to Purkinje cells was selectively and reversibly blocked by doxycycline-dependent expression of transmission-blocking tetanus toxin in granule cells...
April 8, 2014: Proceedings of the National Academy of Sciences of the United States of America
Lei Cao, Jessica Molina, Clemer Abad, Paulina Carmona-Mora, Areli Cárdenas Oyarzo, Juan I Young, Katherina Walz
Potocki-Lupski syndrome (PTLS) is a genomic disorder associated with an ∼3 Mb duplication in 17p11.2. Clinical features include leanness, intellectual disability, autistic features and developmental deficits. RAI1 gene dosage is associated with the PTLS phenotypes. To understand where and when Rai1 overexpression is detrimental, we generated a mouse that over-expresses Rai1 conditionally in forebrain neurons (I-Rai1). Phenotypic characterization of I-Rai1 mice showed significant underweight, hyperactivity and impaired learning and memory ability compared with wild-type littermates...
April 1, 2014: Human Molecular Genetics
Caroline Compain, Karim Sacre, Xavier Puéchal, Isabelle Klein, Denis Vital-Durand, Jean-Luc Houeto, Thomas De Broucker, Didier Raoult, Thomas Papo
Whipple disease (WD) is a rare multisystemic infection with a protean clinical presentation. The central nervous system (CNS) is involved in 3 situations: CNS involvement in classic WD, CNS relapse in previously treated WD, and isolated CNS infection. We retrospectively analyzed clinical features, diagnostic workup, brain imaging, cerebrospinal fluid (CSF) study, treatment, and follow-up data in 18 patients with WD and CNS infection. Ten men and 8 women were included with a median age at diagnosis of 47 years (range, 30-56 yr)...
November 2013: Medicine (Baltimore)
Sebastien Sultan, Elias Gebara, Nicolas Toni
Adult hippocampal neurogenesis results in the continuous formation of new neurons and is a process of brain plasticity involved in learning and memory. Although inducible-reversible transgenic mouse models are increasingly being used to investigate adult neurogenesis, transgene control requires the administration of an activator, doxycycline (Dox), with unknown effects on adult neurogenesis. Here, we tested the effect of Dox administration on adult neurogenesis in vivo. We found that 4 weeks of Dox treatment at doses commonly used for gene expression control, resulted in increased neurogenesis...
2013: Frontiers in Neuroscience
Steve Ramirez, Xu Liu, Pei-Ann Lin, Junghyup Suh, Michele Pignatelli, Roger L Redondo, Tomás J Ryan, Susumu Tonegawa
Memories can be unreliable. We created a false memory in mice by optogenetically manipulating memory engram-bearing cells in the hippocampus. Dentate gyrus (DG) or CA1 neurons activated by exposure to a particular context were labeled with channelrhodopsin-2. These neurons were later optically reactivated during fear conditioning in a different context. The DG experimental group showed increased freezing in the original context, in which a foot shock was never delivered. The recall of this false memory was context-specific, activated similar downstream regions engaged during natural fear memory recall, and was also capable of driving an active fear response...
July 26, 2013: Science
Franz Marxreiter, Benjamin Ettle, Verena E L May, Hakan Esmer, Christina Patrick, Christine Lund Kragh, Jochen Klucken, Beate Winner, Olaf Riess, Jürgen Winkler, Eliezer Masliah, Silke Nuber
In Parkinson's disease (PD) patients, alpha-synuclein (α-syn) pathology advances in form of Lewy bodies and Lewy neurites throughout the brain. Clinically, PD is defined by motor symptoms that are predominantly attributed to the dopaminergic cell loss in the substantia nigra. However, motor deficits are frequently preceded by smell deficiency or neuropsychological symptoms, including increased anxiety and cognitive dysfunction. Accumulating evidence indicates that aggregation of α-syn impairs synaptic function and neurogenic capacity that may be associated with deficits in memory, learning and mood...
November 2013: Neurobiology of Disease
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