Elisabeth J. Van Bockstaele - US grants
Affiliations: | Neuroscience | Thomas Jefferson University, Philadelphia, PA, United States |
Area:
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The funding information displayed below comes from the NIH Research Portfolio Online Reporting Tools and the NSF Award Database.The grant data on this page is limited to grants awarded in the United States and is thus partial. It can nonetheless be used to understand how funding patterns influence mentorship networks and vice-versa, which has deep implications on how research is done.
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High-probability grants
According to our matching algorithm, Elisabeth J. Van Bockstaele is the likely recipient of the following grants.Years | Recipients | Code | Title / Keywords | Matching score |
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1991 — 1992 | Van Bockstaele, Elisabeth J | F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
Cellular Substrates of Mesolimbic Serotonin Modulation @ Weill Medical College of Cornell Univ |
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1994 — 2017 | Van Bockstaele, Elisabeth J | R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. R29Activity Code Description: Undocumented code - click on the grant title for more information. |
Opioid Modulation of the Coeruleo-Cortical Pathway @ Thomas Jefferson University norepinephrine; enkephalins; locus coeruleus; intercellular connection; glutamates; serotonin; central neural pathway /tract; cerebral cortex; immunocytochemistry; laboratory rat; single cell analysis; |
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1996 | Van Bockstaele, Elisabeth J | R29Activity Code Description: Undocumented code - click on the grant title for more information. |
Opioid Modulation of the Coeruleo Cortical Pathway @ Thomas Jefferson University |
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1996 — 1997 | Van Bockstaele, Elisabeth J | 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. |
Mu Opiate Receptor and the Medullocoerulear Pathway @ Thomas Jefferson University DESCRIPTION: (Applicant's Abstract) Neurons located in the nucleus paragigantocellularis (PGi) in the rostral ventral medulla provide a strong opioid and excitatory amino acid projection to the nucleus locus coeruleus (LC) in the dorsal pontine tegmentum. The LC is solely responsible for providing norepinephrine to the forebrain and activation of neurons in this brain region has been correlated with changes in behavioral state and a general increase in sympathetic activity. Several lines of evidence have recently implicated the PGi/LC pathway in the mediation of the physical and adverse signs observed in animals upon withdrawal from opiates. Specifically, neurons in the LC of opiate dependent rats have been reported to have significant increases in their discharge rates following cessation of opiate administration or by precipitation of opiate withdrawal with an opiate antagonist. This increase in neuronal activity has been reported to be caused by an efflux of excitatory amino acids from axon terminals in the LC most likely deriving from the PGi. Activation of glutamate-containing neurons in the PGi may depend on direct synaptic activation of the morphine-like mu-opiate receptor by endogenous opioid peptides on LC-projecting neurons in the PGi which subsequently affect glutamate release in the LC. The recent production of antibodies directed against such receptors can be used to examine the sites of actions of their endogenous ligands. The specific aims of the proposed studies address fundamental questions regarding anatomical substrates responsible for mediating LC activation during opiate withdrawal. Aim 1 will examine whether the mu-selective opiate receptor is localized on (1) plasmalemmal sites of LC-projecting neurons in the PGi and (2) axon terminals which are presynaptic to LC-projecting neurons in the PGi. Aim 11 will determine the cellular substrates for proposed inter-actions between PGi afferent terminals, enkephalin afferents and the mu- selective receptor. The methods include dual labeling immunocytochemistry and tract-tracing at the electron microscopic level in adult rat brain. Ultrastructural analysis is a powerful technique to determine directly whether receptors are neuronal or glial, as well as their pre- and postsynaptic locations on identified neurons. This methodology permits the direct visualization of sites representing the functional expression of identified receptors. Ultrastructural immunocytochemical localization of neuro-transmitters and receptors also complement pharmacological and physiological studies in which direct and indirect interactions are difficult, if not impossible, to differentiate. The results will serve to verify and qualify the cellular mechanisms through which opiate receptor activation and excitatory amino acids may regulate neuronal activity in the PGi/LC pathway. Elucidation of the anatomical substrates in the medullo-coerulear circuit may provide a model for our under-standing of the neural circuits involved in drug dependence in humans. These studies will lay the necessary groundwork for future studies directed at examing potential changes in mu-opiate receptor density and distribution in naive versus opiate dependent animals. |
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2002 — 2006 | Van Bockstaele, Elisabeth J | K02Activity Code Description: Undocumented code - click on the grant title for more information. |
Opioids, Stress and Noradrenergic Neurons @ Thomas Jefferson University DESCRIPTION (provided by applicant): This application for a K02 Independent Scientist Award is submitted to enable me to devote additional time to research-related projects and foster my career in the field of opiate and stress research. I have recently received federal grant support from the National Institute on Drug Abuse (NIDA) (R0 I DA09082-05) for five years (2001-2006). The project entitled "Opioid modulation of the coeruleo-cortical pathway" is a continuation of a project originally funded as an HRST Award by NIDA. The proposed studies involve collaborations with two other investigators in Philadelphia, Dr. Rita Valentino, a Professor at the Children's Hospital of Philadelphia and Dr. Michelle Page, a Research Assistant Professor at Hahnemann/Medical College of Pennsylvania. The Specific Aims of the project integrate neuroanatomical approaches to provide cellular substrates for interactions between opioids and corticotropin releasing factor (CRF) that impact on noradrenergic neurons of the locus coeruleus (LC), neurophysiological approaches to identify the impact of CRF-opioid interactions on LC neuronal activity and neurochernical approaches to determine whether these interactions are translated to cortical targets. The guiding hypothesis is that stress engages CRF and opioid afferents to the LC that have opposing influences on this system. The balance between opioid and CRF influences may maintain the balance of active and passive coping behaviors in response to stress. Changes in LC sensitivity to either opioids (as a result of opioid tolerance) or CRF (as a result of prior stress) would shift this balance and the pattern of active vs. passive coping behaviors. These collaborative efforts would enable me to explore new techniques and experimental approaches. Moreover, collaborations with faculty within the Department of Pathology, Anatomy and Cell Biology at Thomas Jefferson University described in Aim 3 of the present proposal have been initiated to enhance my career development. Experiments include laser capture microdissection combined with microarray technology to examine differences in gene expression in LC neurons following exposure to opiates or swim stress. Appropriate training in the responsible conduct of research is also described within the application. |
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2003 — 2005 | Van Bockstaele, Elisabeth J | 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.) |
Very Low Naltrexone Treatment of Opiate Withdrawal @ Thomas Jefferson University DESCRIPTION (provided by applicant): It is the intention of this R21 application to gather data regarding the feasibility of a novel opiate detoxification method, with the use of very low-dose naltrexone pretreatment to reduce withdrawal symptoms in morphine dependent rats. Pharmacological withdrawal management is often the first step in the treatment of opiate dependent patients. Although a wide range of detoxification techniques have been employed, there is a continuing search for more effective approaches. Recently, the use of opiate antagonists (i.e. naltrexone, naloxone) in detoxification protocols has been introduced to sharply decrease withdrawal duration, but at the cost of greatly increased symptom intensity requiring heavy sedation and even anesthesia. Resulting serious medical complications has discouraged and limited the use of this approach. On the other hand, experimental evidence on analgesic and dependence-reducing properties of very low doses of opiate antagonists points to an alternative strategy for the use of these antagonist drugs during detoxification. Although the behavioral manifestations of opiate withdrawal have been thoroughly described in animal models, the cellular bases underlying these changes have only recently been characterized. Several brain nuclei exhibit immediate early gene expression (e.g. c-fos), which is used as a marker of neuronal activation, in the course of withdrawal. Furthermore, alterations in intracellular messengers, including cyclic adenosine monophosphate (cAMP)-dependent protein kinases (PKA), and cAMP-response element-binding protein (CREB) have been shown following opiate withdrawal in the central nervous system. Specific purpose of this study is to test the hypothesis that pretreatment of opiate dependent rats with very-low doses of opiate antagonists ameliorates behavioral and biochemical expressions of withdrawal. Experiments in Aim I are proposed to examine whether naltrexone pretreatment reduces the aversive and somatic signs of withdrawal. To this end, behavioral expression of withdrawal will be rated according to a well-described score of behaviors. Aim II will examine the distribution of c-fos protein in brain regions known to be activated following withdrawal to test whether very low-dose naltrexone pretreatment diminishes the expression of c-fos in these brain areas. Finally, Aim Ill will use western blot analysis to examine levels of intracellular messengers known to be increased during withdrawal to determine whether these are altered following pretreatment with low-doses of naltrexone. The information collected will provide the necessary foundation for designing detoxification trials in humans. |
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2005 — 2017 | Van Bockstaele, Elisabeth J | R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Modulation of Norepinephrine by Cannabinoids @ Thomas Jefferson University [unreadable] DESCRIPTION (provided by applicant): The existence of an endogenous cannabinoid system, comprising cannabinoid receptors and endogenous ligands is now well recognized. However, the distribution of cannabinoid receptors and the impact of cannabinoid agonists on monoaminergic neurotransmitter systems is only slowly beginning to emerge. This information is essential for understanding cellular adaptations following chronic recreational drug exposure as well as elucidating potential therapeutic uses for cannabinoid-based compounds. Acute effects of cannabinoid receptor agonist administration include deficits in learning and memory, distorted perception, difficulty in problem solving and loss of coordination. Repeated administration leads to increases in the activation of the stress-response system, anxiety, depression, cognitive impairment, and psychosis. The question remains as to where cannabinoids act to induce cellular adaptations that may result in long term behavioral dysfunction. Preliminary data from our laboratories suggest that one potential target is the noradrenergic coeruleo-cortical pathway, a biogenic amine system involved in modulating higher cognitive function and mood. This system is implicated in setting the attentional mode, and is engaged as part of the stress response to facilitate arousal. Our guiding hypothesis is that chronic cannabinoid administration results in a potentiated noradrenergic system that may contribute to the pathophysiology of affective disorders. The proposed aims, which integrate neuroanatomical, neurochemical and behavioral approaches, promise to further our understanding of the cellular substrates for cannabinoid receptor modulation of the locus coeruleus (LC)-frontal cortex pathway and reveal the participation of this circuit in cannabinoid-induced anxiety. Four specific aims are proposed to answer the following questions: 1) What are the cellular sites mediating cortical norepinephrine efflux induced by cannabinoids ? 2) What is the neuroanatomical distribution of CB1 receptors in the frontal cortex and LC ? 3) Does repeated administration of cannabinoid agonists result in long term effects on noradrenergic function (as detected by increases in tyrosine hydroxylase gene express and release) 4) What are the effects of noradrenergic lesions on cannabinoid-induced anxiety ? By accomplishing the proposed specific aims, we will have a firm understanding of the cellular sites of action of cannabinoids on brain noradrenergic function and the behavioral consequences of chronic exposure to cannabinoids on the noradrenergic system. [unreadable] [unreadable] [unreadable] |
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2018 — 2019 | Thomas, Steven A (co-PI) [⬀] Van Bockstaele, Elisabeth J |
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.) |
Norepinephrine: a Novel Regulator of Amyloid Beta-42 Peptides @ Drexel University Project Summary: Convergent evidence from clinical and preclinical studies have highlighted the deleterious effects of aberrant accumulation of the amyloid beta (A?42) peptide, from neuronal dysfunction to behavioral and psychological manifestations of disease. Compelling evidence from recent clinical studies reveal that elevated levels of A?42 peptides are associated with anxiety and depression symptoms in middle-aged and older non-demented adults, as well as those with mild cognitive impairment (MCI) or in early stages of Alzheimer's disease (AD). Stress is a risk factor for psychiatric disease, as well as for developing AD. Further, it has been demonstrated that amplification of the stress system disrupts cellular and molecular processes at the synapse, promoting the production and secretion of A?42 peptides. The norepinephrine (NE)- locus coeruleus (LC) system is a stress-responsive neurocircuit implicated in stress-related psychiatric disorders, and in the etiology and progression of AD. Numerous studies in the literature support a role for NE as a regulator of A?42 peptide levels, as there are cellular mechanisms by which NE can influence both the production and the degradation and clearance of A?42 peptides. However, there exist significant gaps in knowledge regarding how NE regulates A?42 peptide levels. Early dysregulation of the NE system is thought to underlie the behavioral and psychiatric symptoms of dementia (BPSD), which are often the first symptoms observed in MCI patients that later progress to AD. Because NE can exert profound effects on the production and clearance of A?42 peptides, the dysregulation of NE under conditions of chronic stress, psychiatric disease, or LC degeneration may directly contribute to aberrant accumulation of A?42 peptides. Thus, targeting the LC-NE system may be a novel avenue to modulate A?42 levels in early stages to slow or halt the progression of disease. The proposed studies aim to investigate the role of NE in regulating amyloid beta A?42 peptide levels. We will build on our recent published work showing anatomical localization of A?42 peptides to LC somatodendritic processes and to noradrenergic axon terminals of the naïve male and female rat medial prefrontal cortex (mPFC), a region important for the integration of the stress response and a major projection site of LC neurons. We also examined consequences of NE depletion on A?42 peptides using genetic deletion of D?H, the NE synthesizing enzyme. Results showed that NE depletion significantly decreased levels of A?42 peptides as measured by ELISA. Moreover, in a model that utilizes increased excitatory input to augment LC activity, simulating chronic stress, there is increased localization of A?42 to somatodendritic processes of the LC. These data have informed our current approach to examine dynamic regulation of A?42 levels following LDOPS administration in D?H knockout mice and in D?H-CRE x floxed Adra2a mice, a more direct model of increased NE transmission. Both males and females will be examined to probe for potential sex differences in mechanism of action of NE on A?42 peptide levels. |
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