Publications by authors named "John J Marshall"

12 Publications

  • Page 1 of 1

Invasive imaging of myocardial infarction patients: Is less or more better?

Catheter Cardiovasc Interv 2020 03;95(4):704-705

Department of Cardiovascular Medicine, Northside Cardiovascular Institute, Atlanta, Georgia.

Advanced intravascular imaging or fractional flow reserve in acute myocardial infarction patients may be safely performed and may be associated with clinical benefits. Since this is a nonrandomized registry with too few numbers to adequately evaluate mortality, it is uncertain whether clinical outcomes are truly improved. Adequately powered randomized trials using advanced imaging versus angiographic guided percutaneous coronary intervention (PCI) would be helpful.
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http://dx.doi.org/10.1002/ccd.28793DOI Listing
March 2020

Photoactivatable drugs for nicotinic optopharmacology.

Nat Methods 2018 05 26;15(5):347-350. Epub 2018 Mar 26.

Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia, USA.

Photoactivatable pharmacological agents have revolutionized neuroscience, but the palette of available compounds is limited. We describe a general method for caging tertiary amines by using a stable quaternary ammonium linkage that elicits a red shift in the activation wavelength. We prepared a photoactivatable nicotine (PA-Nic), uncageable via one- or two-photon excitation, that is useful to study nicotinic acetylcholine receptors (nAChRs) in different experimental preparations and spatiotemporal scales.
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http://dx.doi.org/10.1038/nmeth.4637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5923430PMC
May 2018

Kainate Receptors Inhibit Glutamate Release Via Mobilization of Endocannabinoids in Striatal Direct Pathway Spiny Projection Neurons.

J Neurosci 2018 04 14;38(16):3901-3910. Epub 2018 Mar 14.

Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611 and

Kainate receptors are members of the glutamate receptor family that function by both generating ionotropic currents through an integral ion channel pore and coupling to downstream metabotropic signaling pathways. They are highly expressed in the striatum, yet their roles in regulating striatal synapses are not known. Using mice of both sexes, we demonstrate that GluK2-containing kainate receptors expressed in direct pathway spiny projection neurons (dSPNs) inhibit glutamate release at corticostriatal synapses in the dorsolateral striatum. This inhibition requires postsynaptic kainate-receptor-mediated mobilization of a retrograde endocannabinoid (eCB) signal and activation of presynaptic CB1 receptors. This pathway can be activated during repetitive 25 Hz trains of synaptic stimulation, causing short-term depression of corticostriatal synapses. This is the first study to demonstrate a role for kainate receptors in regulating eCB-mediated plasticity at the corticostriatal synapse and demonstrates an important role for these receptors in regulating basal ganglia circuits. The gene, encoding the GluK2 subunit of the kainate receptor, has been linked to several neuropsychiatric and neurodevelopmental disorders including obsessive compulsive disorder (OCD). Perseverative behaviors associated with OCD are known to result from pathophysiological changes in the striatum and kainate receptor knock-out mice have striatal-dependent phenotypes. However, the role of kainate receptors in striatal synapses is not known. We demonstrate that GluK2-containing kainate receptors regulate corticostriatal synapses by mobilizing endocannabinoids from direct pathway spiny projection neurons. Synaptic activation of GluK2 receptors during trains of synaptic input causes short-term synaptic depression, demonstrating a novel role for these receptors in regulating striatal circuits.
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http://dx.doi.org/10.1523/JNEUROSCI.1788-17.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5907053PMC
April 2018

Delayed Maturation of Fast-Spiking Interneurons Is Rectified by Activation of the TrkB Receptor in the Mouse Model of Fragile X Syndrome.

J Neurosci 2017 11 16;37(47):11298-11310. Epub 2017 Oct 16.

Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611,

Fragile X syndrome (FXS) is a neurodevelopmental disorder that is a leading cause of inherited intellectual disability, and the most common known cause of autism spectrum disorder. FXS is broadly characterized by sensory hypersensitivity and several developmental alterations in synaptic and circuit function have been uncovered in the sensory cortex of the mouse model of FXS ( KO). GABA-mediated neurotransmission and fast-spiking (FS) GABAergic interneurons are central to cortical circuit development in the neonate. Here we demonstrate that there is a delay in the maturation of the intrinsic properties of FS interneurons in the sensory cortex, and a deficit in the formation of excitatory synaptic inputs on to these neurons in neonatal KO mice. Both these delays in neuronal and synaptic maturation were rectified by chronic administration of a TrkB receptor agonist. These results demonstrate that the maturation of the GABAergic circuit in the sensory cortex is altered during a critical developmental period due in part to a perturbation in BDNF-TrkB signaling, and could contribute to the alterations in cortical development underlying the sensory pathophysiology of FXS. Fragile X (FXS) individuals have a range of sensory related phenotypes, and there is growing evidence of alterations in neuronal circuits in the sensory cortex of the mouse model of FXS ( KO). GABAergic interneurons are central to the correct formation of circuits during cortical critical periods. Here we demonstrate a delay in the maturation of the properties and synaptic connectivity of interneurons in KO mice during a critical period of cortical development. The delays both in cellular and synaptic maturation were rectified by administration of a TrkB receptor agonist, suggesting reduced BDNF-TrkB signaling as a contributing factor. These results provide evidence that the function of fast-spiking interneurons is disrupted due to a deficiency in neurotrophin signaling during early development in FXS.
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http://dx.doi.org/10.1523/JNEUROSCI.2893-16.2017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5700416PMC
November 2017

Complete Disruption of the Kainate Receptor Gene Family Results in Corticostriatal Dysfunction in Mice.

Cell Rep 2017 02;18(8):1848-1857

Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Department of Neurobiology, Weinberg College of Arts and Sciences, Northwestern University, Evanston, IL 60208, USA. Electronic address:

Kainate receptors are members of the glutamate receptor family that regulate synaptic function in the brain. They modulate synaptic transmission and the excitability of neurons; however, their contributions to neural circuits that underlie behavior are unclear. To understand the net impact of kainate receptor signaling, we generated knockout mice in which all five kainate receptor subunits were ablated (5ko). These mice displayed compulsive and perseverative behaviors, including over-grooming, as well as motor problems, indicative of alterations in striatal circuits. There were deficits in corticostriatal input to spiny projection neurons (SPNs) in the dorsal striatum and correlated reductions in spine density. The behavioral alterations were not present in mice only lacking the primary receptor subunit expressed in adult striatum (GluK2 KO), suggesting that signaling through multiple receptor types is required for proper striatal function. This demonstrates that alterations in striatal function dominate the behavioral phenotype in mice without kainate receptors.
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http://dx.doi.org/10.1016/j.celrep.2017.01.073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5327928PMC
February 2017

Epac2 Mediates cAMP-Dependent Potentiation of Neurotransmission in the Hippocampus.

J Neurosci 2015 Apr;35(16):6544-53

Department of Physiology and Department of Neurobiology, Northwestern University Weinberg College of Arts and Sciences, Evanston, Illinois 60208

Presynaptic terminal cAMP elevation plays a central role in plasticity at the mossy fiber-CA3 synapse of the hippocampus. Prior studies have identified protein kinase A as a downstream effector of cAMP that contributes to mossy fiber LTP (MF-LTP), but the potential contribution of Epac2, another cAMP effector expressed in the MF synapse, has not been considered. We investigated the role of Epac2 in MF-CA3 neurotransmission using Epac2(-/-) mice. The deletion of Epac2 did not cause gross alterations in hippocampal neuroanatomy or basal synaptic transmission. Synaptic facilitation during short trains was not affected by loss of Epac2 activity; however, both long-term plasticity and forskolin-mediated potentiation of MFs were impaired, demonstrating that Epac2 contributes to cAMP-dependent potentiation of transmitter release. Examination of synaptic transmission during long sustained trains of activity suggested that the readily releasable pool of vesicles is reduced in Epac2(-/-) mice. These data suggest that cAMP elevation uses an Epac2-dependent pathway to promote transmitter release, and that Epac2 is required to maintain the readily releasable pool at MF synapses in the hippocampus.
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http://dx.doi.org/10.1523/JNEUROSCI.0314-14.2015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4405561PMC
April 2015

Potentiating mGluR5 function with a positive allosteric modulator enhances adaptive learning.

Learn Mem 2013 Jul 18;20(8):438-45. Epub 2013 Jul 18.

Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.

Metabotropic glutamate receptor 5 (mGluR5) plays important roles in modulating neural activity and plasticity and has been associated with several neuropathological disorders. Previous work has shown that genetic ablation or pharmacological inhibition of mGluR5 disrupts fear extinction and spatial reversal learning, suggesting that mGluR5 signaling is required for different forms of adaptive learning. Here, we tested whether ADX47273, a selective positive allosteric modulator (PAM) of mGluR5, can enhance adaptive learning in mice. We found that systemic administration of the ADX47273 enhanced reversal learning in the Morris Water Maze, an adaptive task. In addition, we found that ADX47273 had no effect on single-session and multi-session extinction, but administration of ADX47273 after a single retrieval trial enhanced subsequent fear extinction learning. Together these results demonstrate a role for mGluR5 signaling in adaptive learning, and suggest that mGluR5 PAMs represent a viable strategy for treatment of maladaptive learning and for improving behavioral flexibility.
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http://dx.doi.org/10.1101/lm.031666.113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3718201PMC
July 2013

Cholinergic interneurons in the nucleus accumbens regulate depression-like behavior.

Proc Natl Acad Sci U S A 2012 Jul 25;109(28):11360-5. Epub 2012 Jun 25.

Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065, USA.

A large number of studies have demonstrated that the nucleus accumbens (NAC) is a critical site in the neuronal circuits controlling reward responses, motivation, and mood, but the neuronal cell type(s) underlying these processes are not yet known. Identification of the neuronal cell types that regulate depression-like states will guide us in understanding the biological basis of mood and its regulation by diseases like major depressive disorder. Taking advantage of recent findings demonstrating that the serotonin receptor chaperone, p11, is an important molecular regulator of depression-like states, here we identify cholinergic interneurons (CINs) as a primary site of action for p11 in the NAC. Depression-like behavior is observed in mice after decrease of p11 levels in NAC CINs. This phenotype is recapitulated by silencing neuronal transmission in these cells, demonstrating that accumbal cholinergic neuronal activity regulates depression-like behaviors and suggesting that accumbal CIN activity is crucial for the regulation of mood and motivation.
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http://dx.doi.org/10.1073/pnas.1209293109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3396525PMC
July 2012

Antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) are attenuated by antiinflammatory drugs in mice and humans.

Proc Natl Acad Sci U S A 2011 May 25;108(22):9262-7. Epub 2011 Apr 25.

Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065, USA.

Antiinflammatory drugs achieve their therapeutic actions at least in part by regulation of cytokine formation. A "cytokine hypothesis" of depression is supported by the observation that depressed individuals have elevated plasma levels of certain cytokines compared with healthy controls. Here we investigated a possible interaction between antidepressant agents and antiinflammatory agents on antidepressant-induced behaviors and on p11, a biochemical marker of depressive-like states and antidepressant responses. We found that widely used antiinflammatory drugs antagonize both biochemical and behavioral responses to selective serotonin reuptake inhibitors (SSRIs). In contrast to the levels detected in serum, we found that frontal cortical levels of certain cytokines (e.g., TNFα and IFNγ) were increased by serotonergic antidepressants and that these effects were inhibited by antiinflammatory agents. The antagonistic effect of antiinflammatory agents on antidepressant-induced behaviors was confirmed by analysis of a dataset from a large-scale real-world human study, "sequenced treatment alternatives to relieve depression" (STAR*D), underscoring the clinical significance of our findings. Our data indicate that clinicians should carefully balance the therapeutic benefits of antiinflammatory agents versus the potentially negative consequences of antagonizing the therapeutic efficacy of antidepressant agents in patients suffering from depression.
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http://dx.doi.org/10.1073/pnas.1104836108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107316PMC
May 2011

A role for p11 in the antidepressant action of brain-derived neurotrophic factor.

Biol Psychiatry 2010 Sep 29;68(6):528-35. Epub 2010 Jun 29.

The Rockefeller University, New York, New York, USA.

Background: The protein p11 (also called S100A10) is downregulated in human and rodent depressive-like states. Considerable experimental evidence also implicates p11 in the mechanism of action of antidepressant drugs and electroconvulsive seizures, in part due to its interaction with specific serotonin receptors. Brain-derived neurotrophic factor (BDNF) has been linked to the therapeutic activity of antidepressants in rodent models and humans. In the current study, we investigated whether BDNF regulates p11 in vitro and in vivo.

Methods: We utilized primary neuronal cultures, in vivo analyses of transgenic mice, and behavioral techniques to assess the effects of BDNF on p11.

Results: Results indicate that BDNF stimulates p11 expression through tropomyosin-related kinase B (trkB) receptors and via the mitogen-activated protein kinase signaling pathway. Brain-derived neurotrophic factor-induced changes in p11 in vivo correlate with changes in ligand binding to the 5-hydroxytryptamine receptor 1B, the subcellular localization of which is known to be regulated by p11. Behavioral studies demonstrate that p11 knockout mice are insensitive to the antidepressant actions of BDNF.

Conclusions: Taken together, our data demonstrate that p11 levels are regulated by BDNF in vitro and in vivo and that the antidepressant-like effect of BDNF in two well-established behavioral models requires p11. These data support a role for p11 in the antidepressant activity of neurotrophins.
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http://dx.doi.org/10.1016/j.biopsych.2010.04.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2929288PMC
September 2010

Transient and selective overexpression of D2 receptors in the striatum causes persistent deficits in conditional associative learning.

Proc Natl Acad Sci U S A 2008 Oct 2;105(41):16027-32. Epub 2008 Oct 2.

Department of Neuroscience, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA.

Cognitive deficits in schizophrenia are thought to derive from a hypofunction of the prefrontal cortex (PFC), but the origin of the hypofunction is unclear. To explore the nature of this deficit, we genetically modified mice to model the increase in striatal dopamine D(2) receptors (D(2)Rs) observed in patients with schizophrenia. Previously, we reported deficits in spatial working memory tasks in these mice, congruent with the working memory deficits observed in schizophrenia. However, patients with schizophrenia suffer from deficits in many executive functions, including associative learning, planning, problem solving, and nonspatial working memory. We therefore developed operant tasks to assay two executive functions, conditional associative learning (CAL) and nonspatial working memory. Striatal D(2)R-overexpressing mice show a deficit in CAL because of perseverative behavior, caused by interference from the previous trial. D(2)R up-regulation during development was sufficient to cause this deficit, because switching off the transgene in adulthood did not rescue the phenotype. We validated prefrontal dependency of CAL by using neurotoxic lesions. Lesions of the medial PFC including the anterior cingulate, infralimbic, and prelimbic cortices impair CAL because of increased interference from previously rewarded trials, exactly as observed in D(2)R transgenic mice. In contrast, lesions restricted to the infralimbic and prelimbic cortices have no effect on CAL but impair performance in the nonspatial working memory task. These assays not only give us insight into how excess striatal D(2)Rs affect cognition but also provide tools for studying cognitive endophenotypes in mice.
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http://dx.doi.org/10.1073/pnas.0807746105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2572912PMC
October 2008

Prognostic implication of creatine kinase release after elective percutaneous coronary intervention in the pre-IIb/IIIa antagonist era.

Am Heart J 2003 Jun;145(6):1006-12

Andreas Gruentzig Cardiovascular Center of Emory University School of Medicine, Division of Cardiology, Atlanta, GA, USA.

Background: The significance of mild elevations in cardiac enzymes after an elective percutaneous coronary intervention (PCI) still remains controversial. We evaluated the significance of creatine phosphokinase level (CPK) elevations in a large cohort of patients who had undergone an elective PCI before the IIb/IIIa receptor antagonist era.

Methods: All patients enrolled in the Emory databank from 1981 to 1996 who had an elective PCI were evaluated. We identified 15,637 patients who met our inclusion and exclusion criteria. Patients were divided into 4 groups on the basis of the magnitude of the CPK elevation noted in the post-PCI period: group I (CPK <250 mg/dL, n = 14,512); group II (CPK 250-500 mg/dL, n = 715); group III (CPK 500-750 mg/dL, n = 164); and group IV (CPK >750 mg/dL, n = 246).

Results: CPK elevations were associated with a significant increase in the periprocedure angiographic complications. Angiographic complication rates were 14.6%, 30.5%, 40.2%, and 43.5% in groups I, II, III, and IV, respectively (P <.001). Long-term survival also correlated inversely with the magnitude of CPK elevations. The 10-year survival rates were 73%, 71%, 69%, and 55% in groups I, II, III, and IV, respectively (P <.0001). After multivariate analysis to correct for clinical factors, a CPK elevation of at least 3-times normal (group IV) was found to be an independent predictor of diminished 30-day and long-term survival (hazard ratio 1.84, 95% CI 1.41-2.41, P <.0001). Elevations in CPK <3-times normal (groups II and III) were not independently predictive of poor long-term survival.

Conclusion: A CPK level >3-times normal after an elective PCI is a strong independent predictor of poor long-term prognosis.
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http://dx.doi.org/10.1016/S0002-8703(03)00095-4DOI Listing
June 2003