1998 |
Shumsky, Jed S |
R03Activity Code Description: To provide research support specifically limited in time and amount for studies in categorical program areas. Small grants provide flexibility for initiating studies which are generally for preliminary short-term projects and are non-renewable. |
Prenatal Cocaine Exposure and Seizure Susceptibility @ Allegheny University of Health Sciences
The consequences of prenatal cocaine exposure are of growing concern as a public health issue. Using a well established animal model of prenatal cocaine exposure in rabbits (3 mg/kg cocaine IV, b.i.d. from gestation day 8 (G8) to G29), we will investigate the seizure susceptibility of the offspring in response to IV cocaine administration. The advantage of this model is the ease with which we can perform IV administration, which is more similar to the pharmacokinetics of common patterns of human cocaine use than IP or SC models. Since we have collected a large body of data using this model which demonstrate molecular and neuroanatomical alterations in the GABAergic system as a consequence of prenatal cocaine exposure, we will investigate whether the function of the GABAergic system is altered in terms of its seizure-related responses. To do so, we will measure the seizure susceptibility of the offspring in response to the GABA receptor antagonist bicuculline. In addition, we will compare the seizure- related effects cocaine and bicuculline to determine if these behaviors are produced through a common output pathway. We will attempt to prevent the production of cocaine-elicited seizures with muscimol, a GABA receptor agonist. We will examine the time course of the development of tolerance to both cocaine and bicuculline-elicited seizures, and we will determine whether there is any degree of cross- tolerance between them. Results will be informative concerning the degree of dysfunction of the GABAergic system following prenatal cocaine exposure and will be potentially useful in evaluating the effects of anticonvulsant medications.
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0.957 |
2007 — 2011 |
Shumsky, Jed S |
P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Behavior and Biomechanics |
1 |
2012 — 2013 |
Gao, Wen-Jun (co-PI) [⬀] Meucci, Olimpia (co-PI) [⬀] Shumsky, Jed S Torres, Claudio Aurelio Waterhouse, Barry Dale [⬀] |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Hiv Gp120 and Prefrontal Cortical Function
DESCRIPTION (provided by applicant): The goal of this multi-investigator project is to develop an animal model of HIV neuropathology that can be used to assess: 1) cognitive function, 2) neuronal and non-neuronal degeneration in the prefrontal cortex and 3) electrophysiological properties of cells and circuits in prefrontal cortical networks. With the advent of improved combination antiretroviral therapy, HIV infection has been transformed from a fatal illness to a chronic manageable condition. This trend has resulted in an increasingly large population of aging individuals with prolonged exposure to HIV neurotoxins and to HIV therapeutic interventions. While there are excellent tissue culture models for studying the impact of HIV or HIV therapy on cellular processes, the options for in vivo investigation of the effects o HIV infection or chronic antiretroviral therapy are more limited, particularly as they relate to th aging brain. The ideal model for investigating such issues would provide the opportunity to examine and correlate cognitive performance with electrophysiological indices of neural function and neuropathology across the aging continuum with respect to onset of the HIV infection and progression of ensuing disease processes. The work outlined in this proposal will focus on CNS exposure to the HIV envelope protein gp120 in adult and aged rats and its impact on 1) performance of two prefrontal cortex-dependent behavioral tasks, 2) neuronal excitability and synaptic transmission in the prefrontal cortical circuitry and 3) the degree of neurotoxic insult t neuronal and non-neuronal cells in the prefrontal cortex. The most important aspect of this investigation is the development of an animal model that will have advantages for numerous additional in vivo studies focusing on the broad array of potential agents and mechanisms associated with HIV infection and its treatment, the time course of these events, and their impact on the aging brain. In particular this model will facilitate the identification and development of new targets and new compounds for therapeutic interventions in adult and aging HIV/AIDS patients. Across all inquiries, the model will validate the findings of in vitro tissue culture studies and their relevance to normative functions in the intact central nervous system. PUBLIC HEALTH RELEVANCE: The goal of this multi-investigator project is to develop a model of HIV neuropathology that can be used to assess: 1) executive function in behaving animals, 2) neuronal and non-neuronal degeneration in the prefrontal cortex (PFC) and 3) electrophysiological properties of cells and circuits in PFC networks. Studies will be conducted in adult and aging rats. Specific experiments will focus on CNS exposure to the HIV envelope protein gp120 and characterize its impact on: 1) performance of two PFC-dependent behavioral tasks, 2) neuronal excitability and synaptic transmission in the PFC circuitry and 3) the degree of neurotoxic insult to neuronal and non-neuronal cells in the PFC. The proposed model will have advantages for numerous additional in vivo studies focusing on the broad array of potential agents and mechanisms associated with HIV infection and its treatment, the time course of these events, and their impact on the aging brain.
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1 |
2013 — 2017 |
Shumsky, Jed S |
P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Behavior
CORE B: Behavior Core - Dr. Jed Shumsky and Ms. Kassi Miller, Co-Directors All projects are proposing that rehabiitative therapy is beneficial to regeneration, repair and recovery of function. Behavior is often noted as the final common output of the CNS. It requires the complex coordination of anatomical substrates, molecular and electrophysiological signals of intact anatomical substrates to elucidate seemingly simple behavior like taking a step or discriminating betiween a light touch or a noxious pinch. Therefore, the sensitivity, validity and reliability of rehabilitative and behavioral testing techniques are critical not only to the success of individual projects, but also for the success and interpretation of the Program Project as a whole. The goal of the Behavior Core is to provide a central facility to the Pis to provide rehabilitative training and/or assess the functional significance of rehabilitative or cellular grafting interventions proposed by the Pis. The Behavior Core provides assistance with experimental design, a centralized facility that is outfitted with at least 7 standardized paradigms for rehabilitative training and more than 25 standardized behavioral testing procotols to test motor, sensorimotor, sensory and autonomic function in rodents and cats after spinal cord injury. Finally, the Behavior Core provides individualized hands- on technical training for technical staff, graduate students, postdoctoral fellows, faculty and visiting faculty in behavioral testing or rehabilitative strategies. RELEVANCE (See instructions): The purpose of this PPG is to utilize regenerative and rehabilitative strategies to promote improvements in functional behavioral recovery. It is imperative that standardized rehabilitative and behavioral testing techniques are employed for accurate interpretation of results. The Behavior Core will provide standardized behavioral equipment and training for personnel to ensure reliability and validity of results.
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