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The effect of cannabidiol (CBD) on behavioral and neuroinflammatory consequences of comorbid AUD and PTSD in a rat modelMcGuffin, Bailey, Schwartz, Britta, Wills, Liza, Gass, Justin 25 April 2023 (has links) (PDF)
Alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD) are debilitating conditions that often co-occur, with an estimated 41-79% comorbidity rate. A major concern with the co-occurrence of these disorders is the tendency for one to exacerbate the other. Specifically, symptoms related to PTSD are a significant risk factor for the development of AUD, and alcohol abuse worsens PTSD symptoms. This cycle, along with a lack of effective pharmacological treatment options, leads to significant behavioral and physiological deficits. Additionally, remission for comorbid AUD and PTSD is much more difficult to attain due to exacerbated symptomology and a lack of FDA-approved medications. In recent years, cannabidiol (CBD), a non-psychoactive compound found in cannabis, has been a focus of study due to its therapeutic potential. Researchers have demonstrated the anxiolytic and anti-inflammatory effects of CBD in both humans and animals, showing its promise as a novel therapeutic agent in the treatment of psychiatric disorders. The purpose of this study is to investigate the hypothesis that CBD will reduce fear-related behaviors and neuroinflammation in a rat model of comorbid AUD and PTSD. Our AUD/PTSD model utilized restraint stress and chronic intermittent ethanol exposure procedures. To investigate changes in future stress sensitivity all animals were exposed to a contextual fear conditioning paradigm, which was used to train the animals to associate environmental and auditory cues (environment appearance and tone) with an aversive stimulus (mild foot-shock). 30 minutes prior to each conditioning session, rats received an intraperitoneal injection of CBD (20mg/kg) or 0.9% Saline. Once the animals learned to associate the cues with a shock, they were exposed to an extinction learning procedure that involved presentation of the cue alone (no shock). This procedure parallels exposure therapy in humans, allowing for the assessment adaptations to fear learning. The amount of time the rats remain still (freezing) during the tone represents fear-related behavior. Our current results indicate rats with a history of stress and alcohol exposure displayed significantly higher freezing behaviors and this effect was significantly decreased with CBD treatment. This suggests that when CBD is administered during fear learning, it is able to attenuate heightened stress sensitivity associated with AUD/PTSD. To evaluate how CBD mediates the neuroinflammatory response associated with AUD and PTSD, brains from the rats were extracted and analyzed for the inflammatory cytokine tumor necrosis factor a (TNF-a). Specific regions of interest included the medial prefrontal cortex and hippocampus, areas associated with anxiety, memory, and addiction. Neuroinflammation analyses are still ongoing, however it is predicted that rats who received CBD will show a reduction in inflammation in the medial prefrontal cortex and hippocampus. Taken together, the current results show promise for CBD to reduce enhanced fear-related behavior associated with comorbid AUD and PTSD.
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The effects of perinatal choline supplementation on neuroinflammation in the plaque niche of APP-NL-G-F miceCohen, Benjamin 15 February 2024 (has links)
Alzheimer’s Disease (AD) is a chronic neurodegenerative disease commonly characterized by the aggregation and deposition of insoluble amyloid beta plaques throughout the brain, and by an associated neuroinflammatory response to these plaques involving astrocytes and microglia. Choline is an essential nutrient with diverse functional roles that has emerged as a promising candidate for the treatment of AD. Localized plaque regions in the polymorphic layer in the medial dentate gyrus of the hippocampus and in the cortex were examined in 9-month-old APP-NL-G-F knock-in AD model mice to determine the effects of perinatal choline supplementation on astrocytosis and gliosis associated with amyloid beta. The size of ionized calcium-binding adaptor molecule 1 (Iba1)-positive cells and clusters were larger in control diet APPNL-G-F mice, although the number and total area covered by Iba1+ cells/clusters were decreased compared to those of control diet C57BL6/J mice. In comparison, choline supplementation significantly reduced the size of Iba1+ cells/clusters in APPNL-G-F mice. These results suggest that perinatal choline supplementation ameliorates neuroinflammatory processes associated with amyloid plaques in these 9-month-old APPNL-G-F mice, and that dietary supplementation of choline might serve as an effective treatment for AD. / 2026-02-14T00:00:00Z
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Purinergic Signaling in NeuroinflammationAminin, Dmitry, Illes, Peter 20 January 2024 (has links)
ATP is stored in millimolar concentrations within the intracellular medium but may be
released to extracellular sites either through the damaged plasma membrane or by means of
various transporters. Extracellular ATP or its enzymatic breakdown products, ADP, AMP,
and adenosine, may then stimulate a range of membrane receptors (Rs). These receptors are
classified as belonging to two types termed P2 or P1. P2Rs can be, in addition, subdivided
into the ligand-activated P2X and the G protein-coupled P2Y types. Adenosine acts on
the P1 type of receptor. A further classification identifies seven mammalian subtypes of
P2X1-7 and eight mammalian subtypes of P2YRs (P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12,
P2Y13, P2Y14). P1Rs are either positively (A2A, A2B) or negatively (A1, A3) coupled to
adenylate cyclase via the respective G proteins. Already, such a high number of receptors
suggests that purine-mediated effects at the cellular but especially whole organism level
have an immense variability. Whereas P2XRs respond only the ATP, P2YRs are sensitive
to ATP/ADP, UTP/UDP, or UDP–glucose. Inspection of some articles in this Special
Issue will teach us that the nucleoside guanosine probably possesses a receptor of its
own, that nucleotides can be gradually degraded metabolically to functionally active
nucleotides/nucleosides (see above), and indirect effects by stimulating the synthesis or
decomposition of purines/pyrimidines may also increase functional diversity. Eventually,
P2/P1Rs may interact both with each other as well as with other neurotransmitter receptors.
It is, of course, important to note that, in many cases, receptor (sub)type-preferential
agonists and highly selective antagonists are available for pharmacological analysis.
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Exploring the immunosuppressive properties of various agents in the experimental autoimmune encephalomyelitis models of multiple sclerosisNichols, James Matthew 01 May 2020 (has links)
One of the major focuses for our lab involves examining the immunosuppressive properties of various agents and receptors in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). This dissertation encompasses an investigation of cannabidiol in the EAE model, the endocannabinoid CB1 receptor in the EAE model, staphylococcal superantigens (SAgs) as immunosuppressive agents, and various aspects of the EAE model. The first chapter covers the existing literature pertinent to these studies, the second and third chapters cover the material, methods, and results from the studies, and the fourth chapter is a discussion of how those results fit into the existing body of literature. A fifth chapter has also been included which covers two additional studies designed to develop alternative EAE models for our lab; however, both studies turned out differently than expected. One of the most interesting developments from this final chapter was the discovery of an age dependent difference in the memory T cell response of older mice, which allows for more robust disease to be induced when cells from 6 month old mice are used in the passive EAE (P-EAE) model as opposed to mice 10 weeks of age.
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Effect of the Broad-Spectrum Caspase Inhibitor Q-VD-OPh on Neurodegeneration and Neuroinflammation of Sarin exposed miceShah, Ekta J. 27 August 2014 (has links)
No description available.
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Prostaglandin E2 in Oxidopamine-induced Neuronal Inflammation and InjuryKang, Xu 19 September 2017 (has links)
No description available.
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The Role of Innate Immunity in the Response to IntracorticalMicroelectrodesHermann, John Karl 31 August 2018 (has links)
No description available.
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Macrophage Accumulation Near Injured Neuronal Cell Bodies is Necessary and Sufficient for Peripheral Axon RegenerationNiemi, Jon Paul 08 February 2017 (has links)
No description available.
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The effects of T-lymphocytes on secondary neurodegeneration and recovery of function after experimental spinal contusion injuryJones, T. Bucky 29 September 2004 (has links)
No description available.
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Role of the innate immune response and toll-like receptors following spinal cord injury in the mouseKigerl, Kristina Ann 28 November 2006 (has links)
No description available.
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