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  1. Article ; Online: The Relevance of Animal Models of Social Isolation and Social Motivation for Understanding Schizophrenia: Review and Future Directions.

    Powell, Susan B / Swerdlow, Neal R

    Schizophrenia bulletin

    2023  Volume 49, Issue 5, Page(s) 1112–1126

    Abstract: Background and hypotheses: Social dysfunction in schizophrenia includes symptoms of withdrawal and deficits in social skills, social cognition, and social motivation. Based on the course of illness, with social withdrawal occurring prior to psychosis ... ...

    Abstract Background and hypotheses: Social dysfunction in schizophrenia includes symptoms of withdrawal and deficits in social skills, social cognition, and social motivation. Based on the course of illness, with social withdrawal occurring prior to psychosis onset, it is likely that the severity of social withdrawal/isolation contributes to schizophrenia neuropathology.
    Study design: We review the current literature on social isolation in rodent models and provide a conceptual framework for its relationship to social withdrawal and neural circuit dysfunction in schizophrenia. We next review preclinical tasks of social behavior used in schizophrenia-relevant models and discuss strengths and limitations of existing approaches. Lastly, we consider new effort-based tasks of social motivation and their potential for translational studies in schizophrenia.
    Study results: Social isolation rearing in rats produces profound differences in behavior, pharmacologic sensitivity, and neurochemistry compared to socially reared rats. Rodent models relevant to schizophrenia exhibit deficits in social behavior as measured by social interaction and social preference tests. Newer tasks of effort-based social motivation are being developed in rodents to better model social motivation deficits in neuropsychiatric disorders.
    Conclusions: While experimenter-imposed social isolation provides a viable experimental model for understanding some biological mechanisms linking social dysfunction to clinical and neural pathology in schizophrenia, it bypasses critical antecedents to social isolation in schizophrenia, notably deficits in social reward and social motivation. Recent efforts at modeling social motivation using effort-based tasks in rodents have the potential to quantify these antecedents, identify models (eg, developmental, genetic) that produce deficits, and advance pharmacological treatments for social motivation.
    MeSH term(s) Rats ; Animals ; Schizophrenia ; Motivation ; Social Isolation/psychology ; Psychotic Disorders ; Disease Models, Animal ; Rodentia
    Language English
    Publishing date 2023-07-20
    Publishing country United States
    Document type Review ; Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
    ZDB-ID 439173-1
    ISSN 1745-1701 ; 0586-7614
    ISSN (online) 1745-1701
    ISSN 0586-7614
    DOI 10.1093/schbul/sbad098
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: In vivo mapping of protein-protein interactions of schizophrenia risk factors generates an interconnected disease network.

    McClatchy, Daniel B / Powell, Susan B / Yates, John R

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Genetic analyses of Schizophrenia (SCZ) patients have identified thousands of risk factors. In silico protein-protein interaction (PPI) network analysis has provided strong evidence that disrupted PPI networks underlie SCZ pathogenesis. In this study, we ...

    Abstract Genetic analyses of Schizophrenia (SCZ) patients have identified thousands of risk factors. In silico protein-protein interaction (PPI) network analysis has provided strong evidence that disrupted PPI networks underlie SCZ pathogenesis. In this study, we performed
    Language English
    Publishing date 2023-12-13
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.12.12.571320
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Postnatal Phencyclidine-Induced Deficits in Decision Making Are Ameliorated by Optogenetic Inhibition of Ventromedial Orbitofrontal Cortical Glutamate Neurons.

    Tranter, Michael M / Faget, Lauren / Hnasko, Thomas S / Powell, Susan B / Dillon, Daniel G / Barnes, Samuel A

    Biological psychiatry global open science

    2023  Volume 4, Issue 1, Page(s) 264–274

    Abstract: Background: The orbitofrontal cortex (OFC) is essential for decision making, and functional disruptions within the OFC are evident in schizophrenia. Postnatal phencyclidine (PCP) administration in rats is a neurodevelopmental manipulation that induces ... ...

    Abstract Background: The orbitofrontal cortex (OFC) is essential for decision making, and functional disruptions within the OFC are evident in schizophrenia. Postnatal phencyclidine (PCP) administration in rats is a neurodevelopmental manipulation that induces schizophrenia-relevant cognitive impairments. We aimed to determine whether manipulating OFC glutamate cell activity could ameliorate postnatal PCP-induced deficits in decision making.
    Methods: Male and female Wistar rats (
    Results: Compared with saline-treated rats expressing YFP, PCP-treated rats expressing YFP completed fewer reversals, made fewer win-stay responses, and had lower learning rates. We induced similar performance impairments in saline-treated rats by activating vmOFC glutamate cells (ChR2). Strikingly, PCP-induced performance deficits were ameliorated when the activity of vmOFC glutamate cells was inhibited (halorhodopsin).
    Conclusions: Postnatal PCP-induced deficits in decision making are associated with hyperactivity of vmOFC glutamate cells. Thus, normalizing vmOFC activity may represent a potential therapeutic target for decision-making deficits in patients with schizophrenia.
    Language English
    Publishing date 2023-08-09
    Publishing country United States
    Document type Journal Article
    ISSN 2667-1743
    ISSN (online) 2667-1743
    DOI 10.1016/j.bpsgos.2023.08.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Nicotine-Mediated Recruitment of GABAergic Neurons to a Dopaminergic Phenotype Attenuates Motor Deficits in an Alpha-Synuclein Parkinson's Model.

    Lai, Jessica IChi / Porcu, Alessandra / Romoli, Benedetto / Keisler, Maria / Manfredsson, Fredric P / Powell, Susan B / Dulcis, Davide

    International journal of molecular sciences

    2023  Volume 24, Issue 4

    Abstract: Previous work revealed an inverse correlation between tobacco smoking and Parkinson's disease (PD) that is associated with nicotine-induced neuroprotection of dopaminergic (DA) neurons against nigrostriatal damage in PD primates and rodent models. ... ...

    Abstract Previous work revealed an inverse correlation between tobacco smoking and Parkinson's disease (PD) that is associated with nicotine-induced neuroprotection of dopaminergic (DA) neurons against nigrostriatal damage in PD primates and rodent models. Nicotine, a neuroactive component of tobacco, can directly alter the activity of midbrain DA neurons and induce non-DA neurons in the substantia nigra (SN) to acquire a DA phenotype. Here, we investigated the recruitment mechanism of nigrostriatal GABAergic neurons to express DA phenotypes, such as transcription factor Nurr1 and DA-synthesizing enzyme tyrosine hydroxylase (TH), and the concomitant effects on motor function. Wild-type and α-syn-overexpressing (PD) mice treated with chronic nicotine were assessed by behavioral pattern monitor (BPM) and immunohistochemistry/in situ hybridization to measure behavior and the translational/transcriptional regulation of neurotransmitter phenotype following selective Nurr1 overexpression or DREADD-mediated chemogenetic activation. We found that nicotine treatment led to a transcriptional TH and translational Nurr1 upregulation within a pool of SN GABAergic neurons in wild-type animals. In PD mice, nicotine increased Nurr1 expression, reduced the number of α-syn-expressing neurons, and simultaneously rescued motor deficits. Hyperactivation of GABA neurons alone was sufficient to elicit de novo translational upregulation of Nurr1. Retrograde labeling revealed that a fraction of these GABAergic neurons projects to the dorsal striatum. Finally, concomitant depolarization and Nurr1 overexpression within GABA neurons were sufficient to mimic nicotine-mediated dopamine plasticity. Revealing the mechanism of nicotine-induced DA plasticity protecting SN neurons against nigrostriatal damage could contribute to developing new strategies for neurotransmitter replacement in PD.
    MeSH term(s) Mice ; Animals ; alpha-Synuclein/metabolism ; Parkinson Disease/metabolism ; Dopamine/metabolism ; Nicotine/pharmacology ; Substantia Nigra/metabolism ; Dopaminergic Neurons/metabolism ; GABAergic Neurons/metabolism ; Phenotype
    Chemical Substances alpha-Synuclein ; Dopamine (VTD58H1Z2X) ; Nicotine (6M3C89ZY6R)
    Language English
    Publishing date 2023-02-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms24044204
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  5. Article: Multi-modality imaging and therapeutics used in a case of canine spinal nephroblastoma.

    Slinkard, Powell T / Lana, Susan E / Frank, Chad B / Griffin, Lynn R

    The Canadian veterinary journal = La revue veterinaire canadienne

    2022  Volume 63, Issue 8, Page(s) 811–818

    Abstract: A 4-year-old castrated male golden retriever dog was brought to a veterinary teaching hospital for evaluation of acute progressive paraparesis. Neurological examination indicated a spinal cord lesion between the third thoracic vertebra and third lumbar ... ...

    Abstract A 4-year-old castrated male golden retriever dog was brought to a veterinary teaching hospital for evaluation of acute progressive paraparesis. Neurological examination indicated a spinal cord lesion between the third thoracic vertebra and third lumbar vertebrae. Magnetic resonance imaging (MRI) revealed an intradural, extra medullary, and/or intramedullary mass centered over the eleventh and twelfth thoracic disc space. The dog underwent cytoreductive surgery and histopathologic analysis diagnosed a nephroblastoma. Following this, the dog underwent multimodal therapy, including multiple surgeries, 2 courses of radiation, and combination chemotherapy. The dog had serial restaging using MRI, computed tomography (CT), and fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography throughout the course of therapy. The dog survived 350 d from date of first presentation until humane euthanasia was elected due to worsening of neurologic status. During postmortem examination, extensive infiltration of the spinal cord by nephroblastoma cells was discovered as well as pulmonary metastatic disease. Key clinical message: Based on the literature search, this is the first case in which surgery, radiation therapy, and chemotherapy were all used for the treatment of canine spinal nephroblastoma. This case report details the aggressive nature of a case of canine spinal nephroblastoma despite multi-modal therapy.
    MeSH term(s) Animals ; Dog Diseases/diagnostic imaging ; Dog Diseases/surgery ; Dogs ; Hospitals, Animal ; Hospitals, Teaching ; Kidney Neoplasms/diagnostic imaging ; Kidney Neoplasms/therapy ; Kidney Neoplasms/veterinary ; Magnetic Resonance Imaging/veterinary ; Male ; Positron Emission Tomography Computed Tomography ; Thoracic Vertebrae/diagnostic imaging ; Thoracic Vertebrae/pathology ; Wilms Tumor/diagnostic imaging ; Wilms Tumor/therapy ; Wilms Tumor/veterinary
    Language English
    Publishing date 2022-08-02
    Publishing country Canada
    Document type Case Reports
    ZDB-ID 41603-4
    ISSN 0008-5286
    ISSN 0008-5286
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  6. Article ; Online: C-Reactive Protein: Marker of risk for post-traumatic stress disorder and its potential for a mechanistic role in trauma response and recovery.

    Friend, Samantha F / Nachnani, Rahul / Powell, Susan B / Risbrough, Victoria B

    The European journal of neuroscience

    2020  Volume 55, Issue 9-10, Page(s) 2297–2310

    Abstract: Increasing evidence indicates that inflammation plays a role in PTSD and stress disorder pathophysiology. PTSD is consistently associated with higher circulating inflammatory protein levels. Rodent models demonstrate that inflammation promotes enduring ... ...

    Abstract Increasing evidence indicates that inflammation plays a role in PTSD and stress disorder pathophysiology. PTSD is consistently associated with higher circulating inflammatory protein levels. Rodent models demonstrate that inflammation promotes enduring avoidance and arousal behaviors after severe stressors (e.g., predator exposure and social defeat), suggesting that inflammation may play a mechanistic role in trauma disorders. C-reactive protein (CRP) is an innate acute phase reactant produced by the liver after acute infection and chronic disease. A growing number of investigations report associations with PTSD diagnosis and elevated peripheral CRP, CRP gene mutations, and CRP gene expression changes in immune signaling pathways. CRP is reasonably established as a potential marker of PTSD and trauma exposure, but if and how it may play a mechanistic role is unclear. In this review, we discuss the current understanding of immune mechanisms in PTSD with a particular focus on the innate immune signaling factor, CRP. We found that although there is consistent evidence of an association of CRP with PTSD symptoms and risk, there is a paucity of data on how CRP might contribute to CNS inflammation in PTSD, and consequently, PTSD symptoms. We discuss potential mechanisms through which CRP could modulate enduring peripheral and CNS stress responses, along with future areas of investigation probing the role of CRP and other innate immune signaling factors in modulating trauma responses. Overall, we found that CRP likely contributes to central inflammation, but how it does so is an area for further study.
    MeSH term(s) Biomarkers/metabolism ; C-Reactive Protein/metabolism ; Humans ; Inflammation/complications ; Inflammation/metabolism ; Stress Disorders, Post-Traumatic/diagnosis
    Chemical Substances Biomarkers ; C-Reactive Protein (9007-41-4)
    Language English
    Publishing date 2020-11-23
    Publishing country France
    Document type Journal Article ; Review
    ZDB-ID 645180-9
    ISSN 1460-9568 ; 0953-816X
    ISSN (online) 1460-9568
    ISSN 0953-816X
    DOI 10.1111/ejn.15031
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  7. Article ; Online: Sensorimotor gating deficits in "two-hit" models of schizophrenia risk factors.

    Khan, Asma / Powell, Susan B

    Schizophrenia research

    2017  Volume 198, Page(s) 68–83

    Abstract: Genetic and environmental models of neuropsychiatric disease have grown exponentially over the last 20years. One measure that is often used to evaluate the translational relevance of these models to human neuropsychiatric disease is prepulse inhibition ... ...

    Abstract Genetic and environmental models of neuropsychiatric disease have grown exponentially over the last 20years. One measure that is often used to evaluate the translational relevance of these models to human neuropsychiatric disease is prepulse inhibition of startle (PPI), an operational measure of sensorimotor gating. Deficient PPI characterizes several neuropsychiatric disorders but has been most extensively studied in schizophrenia. It has become a useful tool in translational neuropharmacological and molecular genetics studies because it can be measured across species using almost the same experimental parameters. Although initial studies of PPI in rodents were pharmacological because of the robust predictive validity of PPI for antipsychotic efficacy, more recently, PPI has become standard common behavioral measures used in genetic and neurodevelopmental models of schizophrenia. Here we review "two hit" models of schizophrenia and discuss the utility of PPI as a tool in phenotyping these models of relevant risk factors. In the review, we consider approaches to rodent models of genetic and neurodevelopmental risk factors and selectively review "two hit" models of gene×environment and environment×environment interactions in which PPI has been measured.
    MeSH term(s) Animals ; Disease Models, Animal ; Gait Disorders, Neurologic/etiology ; Gait Disorders, Neurologic/genetics ; Gene-Environment Interaction ; Humans ; Risk Factors ; Schizophrenia/complications ; Schizophrenia/genetics
    Language English
    Publishing date 2017-10-22
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 639422-x
    ISSN 1573-2509 ; 0920-9964
    ISSN (online) 1573-2509
    ISSN 0920-9964
    DOI 10.1016/j.schres.2017.10.009
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  8. Article ; Online: Vowel Duration Discrimination of Children With Childhood Apraxia of Speech: A Preliminary Study.

    Ingram, Susan B / Reed, Vicki A / Powell, Thomas W

    American journal of speech-language pathology

    2019  Volume 28, Issue 2S, Page(s) 857–874

    Abstract: ... duration of the consonant /b/ at 42 ms. Vowel lengths increased in 40-ms increments, ranging from 208 ...

    Abstract Purpose The ability of 5- and 6-year-old male children (23 participants) between the chronological ages of 5;0 and 6;11 (years;months) with childhood apraxia of speech (CAS; n = 9) and with typical development (TD; n = 14) to detect differences in vowel duration of syllable pairs is explored. We asked whether the children with CAS show different patterns of performance on the vowel duration difference experimental task than those of their similarly aged peers with TD. Method A male adult audio-recorded the syllable /bɑ/. The /ɑ/ was digitally lengthened and shortened, while maintaining uniform fundamental frequency and amplitude of the vowel and duration of the consonant /b/ at 42 ms. Vowel lengths increased in 40-ms increments, ranging from 208 to 488 ms. Eight pairs of syllables, 1 with equal length and 7 with differing vowel lengths, were randomly presented to the children 10 times in blocks of 16 pairs via a computer application. Results Numerous complementary analyses indicated patterns of performance differed for children with CAS compared to the children with TD. The children with CAS were notably less accurate in their duration discrimination and evidenced greater variability in their performances across duration difference conditions than their peers with TD, signifying they were generally challenged to discriminate the vowel duration differences. Conclusion These results suggest that CAS, which is more generally considered a motor speech disorder, may have a perceptual component of CAS related to vowel duration discrimination. Further research directions and clinical implications are discussed. Supplemental Material https://doi.org/10.23641/asha.8411876.
    MeSH term(s) Apraxias/physiopathology ; Case-Control Studies ; Child ; Child, Preschool ; Humans ; Male ; Speech Discrimination Tests/methods ; Speech Disorders/physiopathology ; Speech Perception/physiology
    Language English
    Publishing date 2019-07-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1154406-5
    ISSN 1558-9110 ; 1058-0360
    ISSN (online) 1558-9110
    ISSN 1058-0360
    DOI 10.1044/2019_AJSLP-MSC18-18-0113
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  9. Article: Models of neurodevelopmental abnormalities in schizophrenia.

    Powell, Susan B

    Current topics in behavioral neurosciences

    2011  Volume 4, Page(s) 435–481

    Abstract: The neurodevelopmental hypothesis of schizophrenia asserts that the underlying pathology of schizophrenia has its roots in brain development and that these brain abnormalities do not manifest themselves until adolescence or early adulthood. Animal models ...

    Abstract The neurodevelopmental hypothesis of schizophrenia asserts that the underlying pathology of schizophrenia has its roots in brain development and that these brain abnormalities do not manifest themselves until adolescence or early adulthood. Animal models based on developmental manipulations have provided insight into the vulnerability of the developing fetus and the importance of the early environment for normal maturation. These models have provided a wide range of validated approaches to answer questions regarding environmental influences on both neural and behavioral development. In an effort to better understand the developmental hypothesis of schizophrenia, animal models have been developed, which seek to model the etiology and/or the pathophysiology of schizophrenia or specific behaviors associated with the disease. Developmental models specific to schizophrenia have focused on epidemiological risk factors (e.g., prenatal viral insult, birth complications) or more heuristic models aimed at understanding the developmental neuropathology of the disease (e.g., ventral hippocampal lesions). The combined approach of behavioral and neuroanatomical evaluation of these models strengthens their utility in improving our understanding of the pathophysiology of schizophrenia and developing new treatment strategies.
    MeSH term(s) Animals ; Behavioral Symptoms/etiology ; Brain/abnormalities ; Brain/embryology ; Brain/growth & development ; Disease Models, Animal ; Female ; Humans ; Pregnancy ; Prenatal Exposure Delayed Effects ; Risk Factors ; Schizophrenia/epidemiology ; Schizophrenia/etiology ; Schizophrenia/pathology
    Language English
    Publishing date 2011-01-10
    Publishing country Germany
    Document type Journal Article ; Review
    ISSN 1866-3370
    ISSN 1866-3370
    DOI 10.1007/7854_2010_57
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  10. Article ; Online: Acute serotonin 2A receptor activation impairs behavioral flexibility in mice.

    Amodeo, Dionisio A / Hassan, Omron / Klein, Landon / Halberstadt, Adam L / Powell, Susan B

    Behavioural brain research

    2020  Volume 395, Page(s) 112861

    Abstract: Serotonin 2A (5- ... ...

    Abstract Serotonin 2A (5-HT
    MeSH term(s) Adaptation, Physiological/drug effects ; Adaptation, Physiological/physiology ; Amphetamines/pharmacology ; Animals ; Autism Spectrum Disorder/physiopathology ; Behavior, Animal/physiology ; Benzylamines/pharmacology ; Cognition/drug effects ; Disease Models, Animal ; Locomotion/drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Phenethylamines/pharmacology ; Receptor, Serotonin, 5-HT2A/metabolism ; Receptor, Serotonin, 5-HT2A/physiology ; Receptor, Serotonin, 5-HT2C/metabolism ; Receptor, Serotonin, 5-HT2C/physiology ; Reversal Learning/drug effects ; Serotonin/pharmacology ; Serotonin 5-HT2 Receptor Agonists/pharmacology ; Spatial Behavior/drug effects
    Chemical Substances Amphetamines ; Benzylamines ; Phenethylamines ; Receptor, Serotonin, 5-HT2A ; Receptor, Serotonin, 5-HT2C ; Serotonin 5-HT2 Receptor Agonists ; Serotonin (333DO1RDJY) ; 2-(4-chloro-2,5-dimethoxyphenyl)-N-((2-methoxyphenyl)methyl)ethanamine (9FGW3C260N) ; 4-iodo-2,5-dimethoxyphenylisopropylamine (OOM10GW9UE)
    Language English
    Publishing date 2020-08-16
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 449927-x
    ISSN 1872-7549 ; 0166-4328
    ISSN (online) 1872-7549
    ISSN 0166-4328
    DOI 10.1016/j.bbr.2020.112861
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