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  1. Article ; Online: Weapons of stress reduction: (R,S)-ketamine and its metabolites as prophylactics for the prevention of stress-induced psychiatric disorders.

    Chen, Briana K / Denny, Christine A

    Neuropharmacology

    2022  Volume 224, Page(s) 109345

    Abstract: Exposure to stress is one of the greatest contributing factors to developing a psychiatric disorder, particularly in susceptible populations. Enhancing resilience to stress could be a powerful intervention to reduce the incidence of psychiatric disease ... ...

    Abstract Exposure to stress is one of the greatest contributing factors to developing a psychiatric disorder, particularly in susceptible populations. Enhancing resilience to stress could be a powerful intervention to reduce the incidence of psychiatric disease and reveal insight into the pathophysiology of psychiatric disorders. (R,S)-ketamine and its metabolites have recently been shown to exert protective effects when administered before or after a variety of stressors and may be effective, tractable prophylactic compounds against psychiatric disease. Drug dosing, sex, age, and strain in preclinical rodent studies, significantly influence the prophylactic effects of (R,S)-ketamine and related compounds. Due to the broad neurobiological actions of (R,S)-ketamine, a variety of mechanisms have been proposed to contribute to the resilience-enhancing effects of this drug, including altering various transcription factors across the genome, enhancing inhibitory connections from the prefrontal cortex, and increasing synaptic plasticity in the hippocampus. Promisingly, select data have shown that (R,S)-ketamine may be an effective prophylactic against psychiatric disorders, such as postpartum depression (PPD). Overall, this review will highlight a brief history of the prophylactic effects of (R,S)-ketamine, the potential mechanisms underlying its protective actions, and possible future directions for translating prophylactic compounds to the clinic. This article is part of the Special Issue on 'Ketamine and its Metabolites'.
    MeSH term(s) Humans ; Female ; Ketamine/therapeutic use ; Depression, Postpartum/drug therapy ; Hippocampus ; Prefrontal Cortex ; Neuronal Plasticity ; Depression/drug therapy
    Chemical Substances Ketamine (690G0D6V8H)
    Language English
    Publishing date 2022-11-23
    Publishing country England
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 218272-5
    ISSN 1873-7064 ; 0028-3908
    ISSN (online) 1873-7064
    ISSN 0028-3908
    DOI 10.1016/j.neuropharm.2022.109345
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Outsmarting (and outrunning) nature's harsh decree.

    Drew, Michael R / Denny, Christine A

    Nature neuroscience

    2018  Volume 21, Issue 9, Page(s) 1141–1142

    MeSH term(s) Hippocampus ; Learning ; Neurogenesis
    Language English
    Publishing date 2018-08-20
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 1420596-8
    ISSN 1546-1726 ; 1097-6256
    ISSN (online) 1546-1726
    ISSN 1097-6256
    DOI 10.1038/s41593-018-0214-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Editorial: Molecular and Cellular Underpinnings of Age-Related Memory Loss.

    Kosmidis, Stylianos / Denny, Christine A / Dranovsky, Alex / Skoulakis, Efthimios M C

    Frontiers in cell and developmental biology

    2021  Volume 9, Page(s) 743187

    Language English
    Publishing date 2021-08-20
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2021.743187
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  4. Article: Propranolol Administration Modulates Neural Activity in the Hippocampal Hilus During Fear Retrieval.

    Leal Santos, Sofia / Chen, Briana K / Pereira, Guilherme R / Pham, Vananh / Denny, Christine A

    Frontiers in behavioral neuroscience

    2022  Volume 16, Page(s) 919831

    Abstract: Altered fear learning is a strong behavioral component of anxiety disorders such as post-traumatic stress disorder (PTSD). Recent efforts have attempted to combine exposure therapies with drugs that target fear memory retrieval and memory reconsolidation, ...

    Abstract Altered fear learning is a strong behavioral component of anxiety disorders such as post-traumatic stress disorder (PTSD). Recent efforts have attempted to combine exposure therapies with drugs that target fear memory retrieval and memory reconsolidation, in order to improve treatment efficacy. The noradrenergic (NA) signaling system is of particular interest, due to its role in regulating the stress response and its involvement in fear and learning processes. Importantly, propranolol (P), a non-selective β-adrenergic antagonist, has shown the potential in decreasing exaggerated fear in both humans and animal models. In a previous study, we utilized an activity-dependent tagging murine model to determine the neural mechanisms by which propranolol attenuates learned fear. We found that propranolol acutely decreased memory trace reactivation specifically in the dorsal dentate gyrus (dDG), but not in CA3 or CA1. Here, we extended our previous study by investigating whether propranolol additionally altered activity in the hilus, a polymorphic layer that consists of neurons, mossy cells, and GABAergic interneurons. We found that propranolol acutely reduced overall hilar activity in both the dorsal and ventral hilus. Moreover, we report that propranolol significantly altered the activity of parvalbumin (PV)
    Language English
    Publishing date 2022-07-07
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452960-6
    ISSN 1662-5153
    ISSN 1662-5153
    DOI 10.3389/fnbeh.2022.919831
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  5. Article: Sex-Specific Effects of Anxiety on Cognition and Activity-Dependent Neural Networks: Insights from (Female) Mice and (Wo)Men.

    Hunsberger, Holly C / Lee, Seonjoo / Jin, Michelle / Lanio, Marcos / Whye, Alicia / Cha, Jiook / Scarlata, Miranda / Jayaseelan, Keerthana / Denny, Christine A

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Introduction: Neuropsychiatric symptoms (NPS), such as depression and anxiety, are observed in 90% of Alzheimer's disease (AD) patients, two-thirds of whom are women. NPS usually manifest long before AD onset creating a therapeutic opportunity. Here, we ...

    Abstract Introduction: Neuropsychiatric symptoms (NPS), such as depression and anxiety, are observed in 90% of Alzheimer's disease (AD) patients, two-thirds of whom are women. NPS usually manifest long before AD onset creating a therapeutic opportunity. Here, we examined the impact of anxiety on AD progression and the underlying brain-wide neuronal mechanisms.
    Methods: To gain mechanistic insight into how anxiety impacts AD progression, we performed a cross-sectional analysis on mood, cognition, and neural activity utilizing the ArcCreER
    Results: Female AD mice exhibited anxiety-like behavior and cognitive decline at an earlier age than control (Ctrl) mice and male mice. Brain-wide analysis of c-Fos
    Conclusions: While future studies are needed to understand whether anxiety is a predictor, a neuropsychiatric biomarker, or a comorbid symptom that occurs during disease onset, these results suggest that AD network dysfunction is sexually dimorphic, and that personalized medicine may benefit male and female AD patients rather than a one size fits all approach.
    Language English
    Publishing date 2023-07-10
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.07.07.548180
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  6. Article: A multiple

    Stackmann, Michelle / Yelhekar, Tushar D / Meng, Meizhen / Sun, Xiaochen / Nthumba, Joseph / Bulthuis, Nicholas E / Vaughan, Nick / Zhu, Elaine / Lin, Yingxi / Denny, Christine A

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Engrams or memory traces are the neuronal ensembles that collectively store individual experiences. Genetic strategies based on immediate early genes (IEGs), such as : Highlights: The mArc system allows for the tagging of ... ...

    Abstract Engrams or memory traces are the neuronal ensembles that collectively store individual experiences. Genetic strategies based on immediate early genes (IEGs), such as
    Highlights: The mArc system allows for the tagging of two
    Language English
    Publishing date 2024-02-02
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.02.01.578410
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: The effect of rim-off deep lateral orbital decompression on the lateral rectus shape and oculomotor balance.

    Caetano, Fabiana B / Garcia, Denny M / Abbud, Christine M M / Cruz, Antonio A V

    International ophthalmology

    2023  Volume 43, Issue 11, Page(s) 4315–4321

    Abstract: Purpose: The purpose of the study was to measure the effect of rim-off deep lateral decompression for Graves orbitopathy on the lateral rectus muscle path and oculomotor balance.: Methods: Retrospective analysis of the medical records and pre- and ... ...

    Abstract Purpose: The purpose of the study was to measure the effect of rim-off deep lateral decompression for Graves orbitopathy on the lateral rectus muscle path and oculomotor balance.
    Methods: Retrospective analysis of the medical records and pre- and postoperative computed tomography scans of 34 orbits of 23 patients who underwent deep lateral decompression alone. The oculomotor balance of these 23 patients was measured with the alternate cover test and prisms before and after surgery. Bezier functions were used to measure the postoperative path of the lateral rectus in all decompressed orbits.
    Results: Deep lateral decompression induced a curvilinear deformation of the lateral rectus. There was no significant correlation between the position of the point of maximum muscle displacement and the size of the residual lateral wall. The changes in the lateral rectus path had no adverse effects on the oculomotor balance of the patients.
    Conclusions: The location of the curvilinear deformation of the lateral rectus does not depend on the residual segment of the lateral wall. The changes of the lateral rectus path have no deleterious effect on the oculomotor balance.
    MeSH term(s) Humans ; Graves Ophthalmopathy/diagnosis ; Graves Ophthalmopathy/surgery ; Retrospective Studies ; Decompression, Surgical ; Oculomotor Muscles/surgery ; Orbit/diagnostic imaging ; Orbit/surgery
    Language English
    Publishing date 2023-08-10
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 800087-6
    ISSN 1573-2630 ; 0165-5701
    ISSN (online) 1573-2630
    ISSN 0165-5701
    DOI 10.1007/s10792-023-02843-7
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  8. Article: Acute (

    Mastrodonato, Alessia / Pavlova, Ina / Kee, Noelle / McGowan, Josephine C / Mann, J John / Denny, Christine A

    Frontiers in neuroscience

    2022  Volume 16, Page(s) 852010

    Abstract: ...

    Abstract (
    Language English
    Publishing date 2022-04-21
    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.2022.852010
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  9. Article ; Online: Prophylactic (R,S)-Ketamine Is Effective Against Stress-Induced Behaviors in Adolescent but Not Aged Mice.

    Mastrodonato, Alessia / Pavlova, Ina / Kee, Noelle C / Pham, Van Anh / McGowan, Josephine C / Mann, J John / Denny, Christine A

    The international journal of neuropsychopharmacology

    2022  Volume 25, Issue 6, Page(s) 512–523

    Abstract: Background: (R,S)-ketamine, an N-methyl-D-aspartate receptor antagonist, is frequently used as an anesthetic and as a rapid-acting antidepressant. We and others have reported that (R,S)-ketamine is prophylactic against stress in adult mice but have yet ... ...

    Abstract Background: (R,S)-ketamine, an N-methyl-D-aspartate receptor antagonist, is frequently used as an anesthetic and as a rapid-acting antidepressant. We and others have reported that (R,S)-ketamine is prophylactic against stress in adult mice but have yet to test its efficacy in adolescent or aged populations.
    Methods: Here, we administered saline or (R,S)-ketamine as a prophylactic at varying doses to adolescent (5-week-old) and aged (24-month-old) 129S6/SvEv mice of both sexes 1 week before a 3-shock contextual fear-conditioning (CFC) stressor. Following CFC, we assessed behavioral despair, avoidance, perseverative behavior, locomotion, and contextual fear discrimination. To assess whether the prophylactic effect could persist into adulthood, adolescent mice were injected with saline or varying doses of (R,S)-ketamine and administered a 3-shock CFC as a stressor 1 month later. Mice were then re-exposed to the aversive context 5 days later and administered behavioral tests as aforementioned. Brains were also processed to quantify Cyclooxygenase 2 expression as a proxy for inflammation to determine whether the prophylactic effects of (R,S)-ketamine were partially due to changes in brain inflammation.
    Results: Our data indicate that (R,S)-ketamine is prophylactic at sex-specific doses in adolescent but not aged mice. (R,S)-ketamine attenuated learned fear and perseverative behavior in females, reduced behavioral despair in males, and facilitated contextual fear discrimination in both sexes. (R,S)-ketamine reduced Cyclooxygenase 2 expression specifically in ventral Cornu Ammonis region 3 of male mice.
    Conclusions: These findings demonstrate that prophylactic (R,S)-ketamine efficacy is sex, dose, and age dependent and will inform future studies investigating (R,S)-ketamine efficacy across the lifespan.
    MeSH term(s) Animals ; Antidepressive Agents/pharmacology ; Cyclooxygenase 2/pharmacology ; Fear ; Female ; Ketamine/pharmacology ; Male ; Mice ; Stress, Psychological
    Chemical Substances Antidepressive Agents ; Ketamine (690G0D6V8H) ; Cyclooxygenase 2 (EC 1.14.99.1)
    Language English
    Publishing date 2022-03-01
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1440129-0
    ISSN 1469-5111 ; 1461-1457
    ISSN (online) 1469-5111
    ISSN 1461-1457
    DOI 10.1093/ijnp/pyac020
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  10. Article ; Online: Proximodistal Heterogeneity of Hippocampal CA3 Pyramidal Neuron Intrinsic Properties, Connectivity, and Reactivation during Memory Recall.

    Sun, Qian / Sotayo, Alaba / Cazzulino, Alejandro S / Snyder, Anna M / Denny, Christine A / Siegelbaum, Steven A

    Neuron

    2017  Volume 95, Issue 3, Page(s) 656–672.e3

    Abstract: The hippocampal CA3 region is classically viewed as a homogeneous autoassociative network critical for associative memory and pattern completion. However, recent evidence has demonstrated a striking heterogeneity along the transverse, or proximodistal, ... ...

    Abstract The hippocampal CA3 region is classically viewed as a homogeneous autoassociative network critical for associative memory and pattern completion. However, recent evidence has demonstrated a striking heterogeneity along the transverse, or proximodistal, axis of CA3 in spatial encoding and memory. Here we report the presence of striking proximodistal gradients in intrinsic membrane properties and synaptic connectivity for dorsal CA3. A decreasing gradient of mossy fiber synaptic strength along the proximodistal axis is mirrored by an increasing gradient of direct synaptic excitation from entorhinal cortex. Furthermore, we uncovered a nonuniform pattern of reactivation of fear memory traces, with the most robust reactivation during memory retrieval occurring in mid-CA3 (CA3b), the region showing the strongest net recurrent excitation. Our results suggest that heterogeneity in both intrinsic properties and synaptic connectivity may contribute to the distinct spatial encoding and behavioral role of CA3 subregions along the proximodistal axis.
    MeSH term(s) Animals ; Behavior, Animal/physiology ; Entorhinal Cortex/physiology ; Fear/physiology ; Hippocampus/physiology ; Male ; Memory/physiology ; Mice, Inbred C57BL ; Models, Neurological ; Neural Pathways/physiology ; Pyramidal Cells/physiology
    Language English
    Publishing date 2017-08-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 808167-0
    ISSN 1097-4199 ; 0896-6273
    ISSN (online) 1097-4199
    ISSN 0896-6273
    DOI 10.1016/j.neuron.2017.07.012
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