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  1. Article: Prenatal stress unmasks behavioral phenotypes in genetic mouse models of neurodevelopmental disorders.

    Harper, Kathryn M / Harp, Samuel J / Moy, Sheryl S

    Frontiers in behavioral neuroscience

    2023  Volume 17, Page(s) 1271225

    Abstract: Neurodevelopmental disorders (NDDs) are complex conditions characterized by heterogeneous clinical profiles and symptoms that arise in infancy and childhood. NDDs are often attributed to a complicated interaction between genetic risk and environmental ... ...

    Abstract Neurodevelopmental disorders (NDDs) are complex conditions characterized by heterogeneous clinical profiles and symptoms that arise in infancy and childhood. NDDs are often attributed to a complicated interaction between genetic risk and environmental factors, suggesting a need for preclinical models reflecting the combined impact of heritable susceptibility and environmental effects. A notable advantage of "two-hit" models is the power to reveal underlying vulnerability that may not be detected in studies employing only genetic or environmental alterations. In this review, we summarize existing literature that investigates detrimental interactions between prenatal stress (PNS) and genes associated with NDDs, with a focus on behavioral phenotyping approaches in mouse models. A challenge in determining the overall role of PNS exposure in genetic models is the diversity of approaches for inducing stress, variability in developmental timepoints for exposure, and differences in phenotyping regimens across laboratories. Identification of optimal stress protocols and critical windows for developmental effects would greatly improve the use of PNS in gene × environment mouse models of NDDs.
    Language English
    Publishing date 2023-09-22
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2452960-6
    ISSN 1662-5153
    ISSN 1662-5153
    DOI 10.3389/fnbeh.2023.1271225
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Evaluating Fatty Acid Amide Hydrolase as a Suitable Target for Sleep Promotion in a Transgenic TauP301S Mouse Model of Neurodegeneration.

    Martin, Shenée C / Joyce, Kathryn K / Harper, Kathryn M / Harp, Samuel J / Cohen, Todd J / Moy, Sheryl S / Diering, Graham H

    Pharmaceuticals (Basel, Switzerland)

    2024  Volume 17, Issue 3

    Abstract: Sleep disruption is an expected component of aging and neurodegenerative conditions, including Alzheimer's disease (AD). Sleep disruption has been demonstrated as a driver of AD pathology and cognitive decline. Therefore, treatments designed to maintain ... ...

    Abstract Sleep disruption is an expected component of aging and neurodegenerative conditions, including Alzheimer's disease (AD). Sleep disruption has been demonstrated as a driver of AD pathology and cognitive decline. Therefore, treatments designed to maintain sleep may be effective in slowing or halting AD progression. However, commonly used sleep aid medications are associated with an increased risk of AD, highlighting the need for sleep aids with novel mechanisms of action. The endocannabinoid system holds promise as a potentially effective and novel sleep-enhancing target. By using pharmacology and genetic knockout strategies, we evaluated fatty acid amide hydrolase (FAAH) as a therapeutic target to improve sleep and halt disease progression in a transgenic Tau P301S (PS19) model of Tauopathy and AD. We have recently shown that PS19 mice exhibit sleep disruption in the form of dark phase hyperarousal as an early symptom that precedes robust Tau pathology and cognitive decline. Acute FAAH inhibition with PF3845 resulted in immediate improvements in sleep behaviors in male and female PS19 mice, supporting FAAH as a potentially suitable sleep-promoting target. Moreover, sustained drug dosing for 5-10 days resulted in maintained improvements in sleep. To evaluate the effect of chronic FAAH inhibition as a possible therapeutic strategy, we generated FAAH-/- PS19 mice models. Counter to our expectations, FAAH knockout did not protect PS19 mice from progressive sleep loss, neuroinflammation, or cognitive decline. Our results provide support for FAAH as a novel target for sleep-promoting therapies but further indicate that the complete loss of FAAH activity may be detrimental.
    Language English
    Publishing date 2024-02-29
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2193542-7
    ISSN 1424-8247
    ISSN 1424-8247
    DOI 10.3390/ph17030319
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Fentanyl-induced acute and conditioned behaviors in two inbred mouse lines: Potential role for Glyoxalase

    Harp, Samuel J. / Martini, Mariangela / Rosenow, Will / Mesner, Larry D. / Johnson, Hugh / Farber, Charles R. / Rissman, Emilie F.

    Physiology & behavior. 2022 Jan. 01, v. 243

    2022  

    Abstract: ... The current study used two inbred mouse strains, C57BL/6 J and A/J, to investigate the genetics of behavioral ... their activity. Neither effect was noted in A/J mice. We conducted RNA-sequencing on the nucleus accumbens ... with quantitative PCR on RNA from the nucleus accumbens and prefrontal cortex (). In both regions A/J mice had ...

    Abstract An increase in opioid-overdose deaths was evident before the COVID-19 pandemic, and has escalated since its onset. Fentanyl, a highly potent synthetic opioid, is the primary driver of these recent trends. The current study used two inbred mouse strains, C57BL/6 J and A/J, to investigate the genetics of behavioral responses to fentanyl. Mice were tested for conditioned place preference and fentanyl-induced locomotor activity. C57BL/6J mice formed a conditioned place preference to fentanyl injections and fentanyl increased their activity. Neither effect was noted in A/J mice. We conducted RNA-sequencing on the nucleus accumbens of mice used for fentanyl-induced locomotor activity. Surprisingly, we noted few differentially expressed genes using treatment as the main factor. However many genes differed between strains. We validated differences in two genes: suppressor APC domain containing 1 (Sapcd1) and Glyoxalase 1 (Glo1), with quantitative PCR on RNA from the nucleus accumbens and prefrontal cortex (). In both regions A/J mice had significantly higher expression of both genes than did C57BL/6 J. In prefrontal cortex, fentanyl treatment decreased Glo1 mRNA. Glyoxalase 1 catalyzes the detoxification of reactive alpha-oxoaldehydes such as glyoxal and methylglyoxal, is associated with anxiety and activity levels, and its inhibition reduces alcohol intake. We suggest that future studies assess the ability of Glo1 and related metabolites to modify opioid intake.
    Keywords COVID-19 infection ; alcohol drinking ; anxiety ; fentanyl ; gene expression regulation ; locomotion ; metabolites ; mice ; prefrontal cortex ; quantitative polymerase chain reaction ; sequence analysis
    Language English
    Dates of publication 2022-0101
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 3907-x
    ISSN 1873-507X ; 0031-9384
    ISSN (online) 1873-507X
    ISSN 0031-9384
    DOI 10.1016/j.physbeh.2021.113630
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Bonn / Germany

    Z 74/401: Show issues

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  4. Article ; Online: Sexual Differentiation and Substance Use: A Mini-Review.

    Harp, Samuel J / Martini, Mariangela / Lynch, Wendy J / Rissman, Emilie F

    Endocrinology

    2020  Volume 161, Issue 9

    Abstract: The organizational/activational hypothesis suggests that gonadal steroid hormones like testosterone (T) and estradiol (E2) are important at 2 different times during the lifespan when they perform 2 different functions. First steroids "organize" brain ... ...

    Abstract The organizational/activational hypothesis suggests that gonadal steroid hormones like testosterone (T) and estradiol (E2) are important at 2 different times during the lifespan when they perform 2 different functions. First steroids "organize" brain structures early in life and during puberty, and in adults these same hormones "activate" sexually dimorphic behaviors. This hypothesis has been tested and proven valid for a large number of behaviors (learning, memory, social, and sexual behaviors). Sex differences in drug addiction are well established both for humans and animal models. Previous research in this field has focused primarily on cocaine self-administration by rats. Traditionally, observed sex differences have been explained by the sex-specific concentrations of gonadal hormones present at the time of the drug-related behavior. Studies with gonadectomized rodents establishes an activational role for E2 that facilitates vulnerability in females, and when E2 is combined with progesterone, addiction is attenuated. Literature on organizational actions of steroids is sparse but predicts that T, after it is aromatized to E2, changes aspects of the neural reward system. Here we summarize these data and propose that sex chromosome complement also plays a role in determining sex-specific drug-taking behavior. Future research is needed to disentangle the effects of hormones and sex chromosome complement, and we propose the four core genotype mouse model as an effective tool for answering these questions.
    MeSH term(s) Aging/drug effects ; Aging/physiology ; Animals ; Brain/drug effects ; Brain/physiology ; Gonadal Steroid Hormones/pharmacology ; Humans ; Reward ; Risk Factors ; Sex Characteristics ; Sex Differentiation/physiology ; Sex Factors ; Substance-Related Disorders/epidemiology ; Substance-Related Disorders/etiology
    Chemical Substances Gonadal Steroid Hormones
    Language English
    Publishing date 2020-04-17
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 427856-2
    ISSN 1945-7170 ; 0013-7227
    ISSN (online) 1945-7170
    ISSN 0013-7227
    DOI 10.1210/endocr/bqaa129
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Uh III Zs.72: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  5. Article ; Online: Fentanyl-induced acute and conditioned behaviors in two inbred mouse lines: Potential role for Glyoxalase.

    Harp, Samuel J / Martini, Mariangela / Rosenow, Will / Mesner, Larry D / Johnson, Hugh / Farber, Charles R / Rissman, Emilie F

    Physiology & behavior

    2021  Volume 243, Page(s) 113630

    Abstract: ... The current study used two inbred mouse strains, C57BL/6 J and A/J, to investigate the genetics of behavioral ... their activity. Neither effect was noted in A/J mice. We conducted RNA-sequencing on the nucleus accumbens ... with quantitative PCR on RNA from the nucleus accumbens and prefrontal cortex (). In both regions A/J mice had ...

    Abstract An increase in opioid-overdose deaths was evident before the COVID-19 pandemic, and has escalated since its onset. Fentanyl, a highly potent synthetic opioid, is the primary driver of these recent trends. The current study used two inbred mouse strains, C57BL/6 J and A/J, to investigate the genetics of behavioral responses to fentanyl. Mice were tested for conditioned place preference and fentanyl-induced locomotor activity. C57BL/6J mice formed a conditioned place preference to fentanyl injections and fentanyl increased their activity. Neither effect was noted in A/J mice. We conducted RNA-sequencing on the nucleus accumbens of mice used for fentanyl-induced locomotor activity. Surprisingly, we noted few differentially expressed genes using treatment as the main factor. However many genes differed between strains. We validated differences in two genes: suppressor APC domain containing 1 (Sapcd1) and Glyoxalase 1 (Glo1), with quantitative PCR on RNA from the nucleus accumbens and prefrontal cortex (). In both regions A/J mice had significantly higher expression of both genes than did C57BL/6 J. In prefrontal cortex, fentanyl treatment decreased Glo1 mRNA. Glyoxalase 1 catalyzes the detoxification of reactive alpha-oxoaldehydes such as glyoxal and methylglyoxal, is associated with anxiety and activity levels, and its inhibition reduces alcohol intake. We suggest that future studies assess the ability of Glo1 and related metabolites to modify opioid intake.
    MeSH term(s) Animals ; COVID-19 ; Fentanyl/pharmacology ; Humans ; Mice ; Mice, Inbred C57BL ; Pandemics ; SARS-CoV-2
    Chemical Substances Fentanyl (UF599785JZ)
    Language English
    Publishing date 2021-10-26
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 3907-x
    ISSN 1873-507X ; 0031-9384
    ISSN (online) 1873-507X
    ISSN 0031-9384
    DOI 10.1016/j.physbeh.2021.113630
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 747: 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)
    ab Jg. 2022: Lesesaal (EG)

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