NeuroImmune pharmacology and therapeutics最新文献

{"title":"The challenges to detect, quantify, and characterize viral reservoirs in the current antiretroviral era.","authors":"Hector Gutierrez, Eliseo A Eugenin","doi":"10.1515/nipt-2024-0017","DOIUrl":"10.1515/nipt-2024-0017","url":null,"abstract":"<p><p>A major barrier to cure HIV is the early generation of viral reservoirs in tissues. These viral reservoirs can contain intact or defective proviruses, but both generates low levels of viral proteins contribute to chronic bystander damage even in the ART era. Most viral reservoir detection techniques are limited to blood-based, reactivation, and sequencing assays that lack spatial properties to examine the contribution of the host's microenvironment to latency and cure efforts. Currently, little is known about the contribution of the microenvironment to viral reservoir survival, residual viral expression, and associated inflammation. Only a few spatiotemporal techniques are available, and fewer integrate spatial genomics, transcriptomics, and proteomics into the analysis of the viral reservoir microenvironment-all essential components to cure HIV. During the development of these spatial techniques, many considerations need to be included in the analysis to avoid misinterpretation. This manuscript tries to clarify some critical concepts in viral reservoir detection by spatial techniques and the upcoming opportunities for cure efforts.</p>","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":"3 3-4","pages":"211-219"},"PeriodicalIF":0.0,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Motivational dysregulation with melanocortin 4 receptor haploinsufficiency.","authors":"Alex M Steiner, Robert F Roscoe, Rosemarie M Booze, Charles F Mactutus","doi":"10.1515/nipt-2024-0011","DOIUrl":"10.1515/nipt-2024-0011","url":null,"abstract":"<p><p>Obesity, by any standard, is a global health crisis. Both genetic and dietary contributions to the development and maintenance of obesity were integral factors of our experimental design. As mutations of the melanocortin 4 receptors (MC4R) are the leading monogenetic cause of obesity, MC4R haploinsufficient rats were fed a range of dietary fat (0-12 %) in a longitudinal design. Physiological and motivational assessments were performed using a locomotor task, a 5-choice sucrose preference task, an operant task with fixed and progressive ratios, as well as a distraction operant task. Dendritic spine morphology of medium spiny neurons (MSNs) of the nucleus accumbens (NAc), cells with ample D1 and D2 receptors, was also assessed. The percentage of lipid deposits in the liver of each rat was also analyzed using the Area Fraction Fractionator probe for stereological measurements. MC4R haploinsufficiency resulted in a phenotypic resemblance for adult-onset obesity that was exacerbated by the consumption of a high-fat diet. Results from the operant tasks indicate that motivational deficits due to MC4R haploinsufficiency were apparent prior to the onset of obesity and exacerbated by dietary fat consumption after obesity was well established. Moreover, MSN morphology shifted to longer spines with smaller head diameters for the MC4R+/- animals under the high-fat diet, suggesting a potential mechanism for the dysregulation of motivation to work for food. Increasing our knowledge of the neural circuitry/mechanisms responsible for the rewarding properties of food has significant implications for understanding energy balance and the development of obesity.</p>","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":"3 3-4","pages":"237-250"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Build muscles and protect myelin.","authors":"Ahana Bose, Kalipada Pahan","doi":"10.1515/nipt-2024-0015","DOIUrl":"10.1515/nipt-2024-0015","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a chronic and debilitating autoimmune disease of the central nervous system (CNS) in which a CNS-driven immune response destroys myelin, leading to wide range of symptoms including numbness and tingling, vision problems, mobility impairment, etc. Oligodendrocytes are the myelinating cells in the CNS, which are generated from oligodendroglial progenitor cells (OPCs) via differentiation. However, for multiple reasons, OPCs fail to differentiate to oligodendrocytes in MS and as a result, stimulating the differentiation of OPCs to oligodendrocytes is considered beneficial for MS. The β-hydroxy β-methylbutyrate (HMB) is a widely-used muscle-building supplement in human and recently it has been shown that low-dose HMB is capable of stimulating the differentiation of cultured OPCs to oligodendrocytes for remyelination. Moreover, other causes of autoimmune demyelination are the decrease and/or suppression of Foxp3-expressing anti-autoimmune regulatory T cells (Tregs) and upregulation of autoimmune T-helper 1(Th1) and Th17 cells. Experimental autoimmune encephalomyelitis (EAE) is an animal model of MS in which the autoimmune demyelination is nicely visible. It has been reported that in EAE mice, oral HMB upregulates Tregs and decreases Th1 and Th17 responses, leading to remyelination in the CNS. Here, we analyze these newly-described features of HMB, highlighting the putative promyelinating nature of this supplement.</p>","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":"3 3-4","pages":"175-182"},"PeriodicalIF":0.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cannabis use, oral dysbiosis, and neurological disorders","authors":"Amber A. Hazzard, Marice K McCrorey, Tabinda Salman, Douglas E. Johnson, Zhenwu Luo, Xiaoyu Fu, Andrew P. Keegan, Andreana Benitez, Sylvia Fitting, Wei Jiang","doi":"10.1515/nipt-2024-0012","DOIUrl":"https://doi.org/10.1515/nipt-2024-0012","url":null,"abstract":"\u0000 Cannabis (marijuana) is a leafy plant that has medical, recreational, and other uses. Cannabis is socially accepted and widely used throughout the United States. Though cannabis use is increasingly gaining popularity, studies detail the deleterious effects of chronic cannabis smoking on mental health, as well as the immunosuppressive properties of cannabinoids. Additionally, oral dysbiosis induced by cannabis smoking serves as a novel catalyst for neurological abnormalities, potentially possible through microbial translocation via the oral-brain axis. This review summarizes the effects and link of smoking cannabis on neurological abnormalities, immunity, and oral microbiome.","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":"54 48","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141923594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biodegradable cannabidiol: a potential nanotherapeutic for neuropathic pain","authors":"Sana Qayum, Rebecca R. Schmitt, Janvhi S. Machhar, Sonali Garg, Caroline Bass, V. Muthaiah, Tracey A. Ignatowski, Supriya D. Mahajan","doi":"10.1515/nipt-2024-0008","DOIUrl":"https://doi.org/10.1515/nipt-2024-0008","url":null,"abstract":"\u0000 Cannabidiol (CBD) is a promising pharmaceutical agent to treat pain, inflammation, and seizures without the psychoactive effects of delta-9-tetrahydrocannabinol (THC). While CBD is highly lipophilic and can cross the blood-brain barrier (BBB), its bioavailability is limited and clearance is quick, limiting its effectiveness in the brain. To improve its effectiveness, we developed a unique nanoformulation consisting of CBD encapsulated within the biodegradable and biocompatible polymer, methoxy polyethylene glycol-poly(lactic-co-glycolic acid) (mPEG-PLGA). mPEG-PLGA-CBD nanoparticles exhibited negligible cytotoxicity over a range of concentrations in CCK-8 assays performed in human astrocytes and brain microvascular endothelial cells. Furthermore, in an in-vitro BBB model, they exhibited rapid BBB permeability without harming BBB integrity. An in vivo Chronic Constriction Injury animal pain model was employed to study the efficacy of mPEG-PLGA-CBD in doses 1, 3 and 10 mg/kg, and it was found that 45–55 nm CBD nanoparticles with an encapsulation efficiency of 65 % can cross the BBB. Additionally, 3 and 10 mg/kg mPEG-PLGA-CBD nanoformulation provided prolonged analgesia in rats on day 2 and -4 post-injection, which we propose is attributed to the sustained and controlled release of CBD. Future studies are required to understand the pharmacokinetics of this nanoformulation.","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":"6 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141807643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Something to talk about; crosstalk disruption at the neurovascular unit during HIV infection of the CNS","authors":"Kalpani N U Galpayage Dona, Mohammed M. Benmassaoud, Cassandra D. Gipson, Jay P. McLaughlin, Servio H. Ramirez, Allison M. Andrews","doi":"10.1515/nipt-2024-0003","DOIUrl":"https://doi.org/10.1515/nipt-2024-0003","url":null,"abstract":"\u0000 Although treatable with antiretroviral therapy, HIV infection persists in people living with HIV (PLWH). It is well known that the HIV virus finds refuge in places for which antiretroviral medications do not reach therapeutic levels, mainly the CNS. It is clear that as PLWH age, the likelihood of developing HIV-associated neurological deficits increases. At the biochemical level neurological dysfunction is the manifestation of altered cellular function and ineffective intercellular communication. In this review, we examine how intercellular signaling in the brain is disrupted in the context of HIV. Specifically, the concept of how the blood-brain barrier can be a convergence point for crosstalk, is explored. Crosstalk between the cells of the neurovascular unit (NVU) (endothelium, pericytes, astrocytes, microglia and neurons) is critical for maintaining proper brain function. In fact, the NVU allows for rapid matching of neuronal metabolic needs, regulation of blood-brain barrier (BBB) dynamics for nutrient transport and changes to the level of immunosurveillance. This review invites the reader to conceptually consider the BBB as a router or convergence point for NVU crosstalk, to facilitate a better understanding of the intricate signaling events that underpin the function of the NVU during HIV associated neuropathology.","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":"53 18","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141809856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sedation with midazolam in the NICU: implications on neurodevelopment","authors":"Nghi M Nguyen, Gurudutt Pendyala","doi":"10.1515/nipt-2024-0009","DOIUrl":"https://doi.org/10.1515/nipt-2024-0009","url":null,"abstract":"\u0000 The developing brain, particularly in premature infants, is highly susceptible to environmental and pharmacological influences. Premature neonates often require prolonged stays in the NICU, where midazolam (MDZ), a benzodiazepine, is commonly used as a sedative, despite concerns raised by the FDA in 2016 regarding its potential neurological complications in infants. Understanding the long-term effects of MDZ on these vulnerable patients is hindered by ethical considerations and limited research. This review emphasizes the vulnerability of premature infants to sedation and anesthesia and outlines how early exposure to MDZ can impact brain development at both molecular and behavioral levels, drawing from clinical and preclinical data. Additionally, we highlighted existing knowledge gaps and suggested avenues for further research to better comprehend the enduring consequences of MDZ exposure on neurodevelopment in this population.","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":"51 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141806911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"X-chromosome linked genes associated with myeloid cell CNS trafficking contributes to female–male differences in the disease outcome for neuroinflammatory diseases","authors":"Sopiko Darchiashvili, Ratuja Kulkarni, Ritesh Tandon, Peter Deak, Kayla L. Nguyen, Pooja Jain","doi":"10.1515/nipt-2024-0007","DOIUrl":"https://doi.org/10.1515/nipt-2024-0007","url":null,"abstract":"\u0000 Certain diseases such as Multiple Sclerosis (MS), a chronic demyelinating disease, affect more women than men, despite males appearing to be predisposed to infections and malignancies. X-linked genes contribute to increased MS susceptibility. Currently, an immense body of research exists that explores the complexity surrounding underlying risk factors for MS development including X-chromosome-linked inflammatory processes. Female–male disparities in disease susceptibility have been found at both the gene and chromosomal level. Genes such as CXORF21 and DDX3X can escape X-chromosome inactivation (XCI) and contribute to various disease pathogenesis. Additionally, blocking immune cell entry to the central nervous system (CNS) can have a major impact on MS. Prior research on MS has shown that immune cells such as T cells and dendritic cells (DCs) infiltrate the CNS. Due to persistent tissue stress, these cells may induce local inflammation and autoimmunity, subsequent neurodegeneration, and both the onset and progression of MS. Chemokines are signaling proteins which regulate leukocyte trafficking to the site of injury, contributing to cell recruitment, CNS inflammation, and disease severity. Some chemokine receptors (CXCR3) are X-linked and may escape XCI. This review provides an account of the contribution of x-linked genes in MS in relation to the chemotaxis of myeloid cells into CNS and subsequent neuroinflammation. The impact of the X-chromosome on autoimmunity, including XCI and the expression of X-linked genes is evaluated. Collectively, the analyses from this review seek to advance both our understanding of MS and advocate for more patient-specific therapies.","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":"43 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141654052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Viral-mediated inflammation by Poly I:C induces the chemokine CCL5 in NK cells and its receptors CCR1 and CCR5 in microglia in the neonatal rat cerebellum","authors":"Miguel Perez-Pouchoulen, Amanda S. Holley, E. Reinl, J. VanRyzin, Amir Mehrabani, Christie Dionisos, Muhammed Mirza, Margaret M. McCarthy","doi":"10.1515/nipt-2024-0002","DOIUrl":"https://doi.org/10.1515/nipt-2024-0002","url":null,"abstract":"\u0000 \u0000 \u0000 To study the effect of viral inflammation induced by Polyinosinic:polycytidylic acid (PIC) on the cerebellum during a critical period of development in rats.\u0000 \u0000 \u0000 \u0000 Neonatal rat pups were treated with PIC on postnatal days (PN) 8 and 10 after which we quantified RNA using Nanostring, qRT-PCR and RNAscope and analyzed immune cells through flow cytometry and immunohistochemistry on PN11. Using the same paradigm, we also analyzed play juvenile behavior, anxiety-like behavior, motor balance using the balance beam and the rotarod assays as well as fine motor behavior using the sunflower seed opening test.\u0000 \u0000 \u0000 \u0000 We determined that male and female pups treated with PIC reacted with a significant increase in CCL5, a chemotactic cytokine that attracts T-cells, eosinophils and basophils to the site of inflammation, at PN11. PIC treatment also increased the expression of two receptors for CCL5, CCR1 and CCR5 in the cerebellar vermis in both males and females at PN11. In-situ hybridization (RNAscope®) for specific transcripts revealed that microglia express both CCL5 receptors under inflammatory and non-inflammatory conditions in both males and females. PIC treatment also increased the total number of CCL5+ cells in the developing cerebellum which were determined to be both natural killer cells and T-cells. There were modest but significant impacts of PIC treatment on large and fine motor skills and juvenile play behavior.\u0000 \u0000 \u0000 \u0000 Our findings suggest an important role for CCL5 and other immune cells in mediating inflammation in the developing cerebellum that potentially impact the maturation of cerebellar neurons during a critical period of development.\u0000","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":"58 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140666895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sera from people with HIV and depression induce commensurate metabolic alterations in astrocytes: toward precision diagnoses and therapies","authors":"A. Laird, Alexandra Anh Le, J. Kulbe, A. Umlauf, Melody Sagarian, Matthew Spencer, Anish Sathe, D. Grelotti, J. Iudicello, Brook Henry, Ronald J. Ellis, J. Fields","doi":"10.1515/nipt-2024-0001","DOIUrl":"https://doi.org/10.1515/nipt-2024-0001","url":null,"abstract":"\u0000 \u0000 \u0000 People with HIV (PWH) have high rates of depression and neurocognitive impairment (NCI) despite viral suppression on antiretroviral therapy (ART). Mounting evidence suggests that immunometabolic disruptions may contribute to these conditions in some PWH. We hypothesized that metabolic dysfunction in astrocytes is associated with depressive symptoms and cognitive function in PWH.\u0000 \u0000 \u0000 \u0000 Human astrocytes were exposed to sera from PWH (n=40) with varying degrees of depressive symptomatology and cognitive function. MitoTrackerTM Deep Red FM (MT) was used to visualize mitochondrial activity and glial fibrillary acidic protein (GFAP) as an indicator of astrocyte reactivity using the high-throughput fluorescent microscopy and image analyses platform, CellInsight CX5 (CX5). The Seahorse platform was used to assess glycolytic and mitochondrial metabolism. \u0000 \u0000 \u0000 \u0000 More severe depression, as indexed by higher Beck's Depression Inventory (BDI-II) scores, was associated with lower MT signal measures. Better cognitive function, as assessed by neuropsychiatric testing t-scores, was associated with increased MT signal measures. GFAP intensity negatively correlated with several cognitive t-scores. Age positively correlated with (higher) MT signal measures and GFAP intensity. Worse depressive symptoms (higher BDI-II scores) were associated with decreased oxygen consumption rate and spare respiratory capacity, concomitant with increased extracellular acidification rate in astrocytes.\u0000 \u0000 \u0000 \u0000 These findings show that factors in the sera of PWH alter mitochondrial activity in cultured human astrocytes, suggesting that mechanisms that alter mitochondrial and astrocyte homeostasis can be detected peripherally. Thus, in vitro cultures may provide a model to identify neuropathogenic mechanisms of depression or neurocognitive impairment in PWH and test personalized therapeutics for neurologic and psychiatric disorders.\u0000","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":"62 26","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140376610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}