NeuroImmune pharmacology and therapeutics最新文献_第2页

Sex dependent correlation of spleen atrophy and behavior deficits induced by binge treatment with ethanol in rodent models. 酒精暴饮暴食致小鼠脾萎缩与行为缺陷的性别相关性研究。

NeuroImmune pharmacology and therapeutics Pub Date : 2024-12-11 eCollection Date: 2025-03-01 DOI: 10.1515/nipt-2024-0016

Jonathan Zhang, Muhammed Bishir, Wenfei Huang, Sulie L Chang

{"title":"Sex dependent correlation of spleen atrophy and behavior deficits induced by binge treatment with ethanol in rodent models.","authors":"Jonathan Zhang, Muhammed Bishir, Wenfei Huang, Sulie L Chang","doi":"10.1515/nipt-2024-0016","DOIUrl":"10.1515/nipt-2024-0016","url":null,"abstract":"Objectives: During physical and psychosocial development, many adolescents engage in binge alcohol drinking. Ethanol (EtOH) is the key chemical in alcoholic beverages. EtOH intoxication impairs locomotor behaviors. We previously found that binge treatment with EtOH (BE) causes spleen atrophy, leading to immune dysregulation. With these premises, we hypothesized that BE-induced spleen atrophy is correlated with compromised locomotion and behaviors in adolescence.Methods: We exposed F344 rats to either 3 days of BE (mimicking college drinking) or water following pubertal onset. 24 h following the last BE, we assessed behaviors using ANY-Maze, focusing on locomotor activity, freezing, and thigmotaxis, before spleen collection. Correlation analysis and Linear Regression analysis quantified BE's effects on behavior. In parallel, we used GEO2R to obtain differentially expressed genes (DEGs) from public dataset GSE49028 (B6129Sf2/J mice were given BE) and identified signaling pathways in the prefrontal cortex (PFC) involved in BE compromising locomotion and increasing anxiety.Results: BE significantly decreased spleen size. Interestingly, we found that BE exposure had a gender-dependent impact, affecting males more than females. Furthermore, functional analysis of the dataset identified several targets of interest including the downregulation of BDNF as a critical regulator of behavioral deficit following BE treatment.Conclusions: Using data-driven discovery and hypothesis-testing investigation to integrate these two studies, we provide an understanding of the underlying biological mechanism of BE-induced spleen atrophy-associated behavioral impairments through the genetic alterations in the PFC. Our findings will help develop a potent, powerful cocktail of reagents to treat behavioral impairment in those who binge drink.","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":"4 1","pages":"59-75"},"PeriodicalIF":0.0,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029036","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}

引用次数: 0

The challenges to detect, quantify, and characterize viral reservoirs in the current antiretroviral era. 在当前抗逆转录病毒时代检测、量化和表征病毒库的挑战。

NeuroImmune pharmacology and therapeutics Pub Date : 2024-12-05 eCollection Date: 2024-09-01 DOI: 10.1515/nipt-2024-0017

Hector Gutierrez, Eliseo A Eugenin

{"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":"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.","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}

引用次数: 0

Motivational dysregulation with melanocortin 4 receptor haploinsufficiency. 动机失调与黑素皮质素4受体单倍不足。

NeuroImmune pharmacology and therapeutics Pub Date : 2024-11-20 eCollection Date: 2024-09-01 DOI: 10.1515/nipt-2024-0011

Alex M Steiner, Robert F Roscoe, Rosemarie M Booze, Charles F Mactutus

{"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":"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.","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}

引用次数: 0

Elevated cerebral oxygen extraction in patients with post-COVID conditions. 新冠肺炎后患者脑氧提取水平升高

NeuroImmune pharmacology and therapeutics Pub Date : 2024-11-20 eCollection Date: 2024-09-01 DOI: 10.1515/nipt-2024-0014

Peiying Liu, Thomas Ernst, Huajun Liang, Dengrong Jiang, Eric Cunningham, Meghann Ryan, Hanzhang Lu, Shyamasundaran Kottilil, Linda Chang

{"title":"Elevated cerebral oxygen extraction in patients with post-COVID conditions.","authors":"Peiying Liu, Thomas Ernst, Huajun Liang, Dengrong Jiang, Eric Cunningham, Meghann Ryan, Hanzhang Lu, Shyamasundaran Kottilil, Linda Chang","doi":"10.1515/nipt-2024-0014","DOIUrl":"10.1515/nipt-2024-0014","url":null,"abstract":"Objectives: Dysfunction of cerebral microcirculation due to SARS-CoV-2 infection has been postulated to be a plausible mechanism for the neurological symptoms of post-COVID-19 conditions (neuro-PCC), affecting oxygen homeostasis in the brain. In this study, we aimed to investigate the balance between cerebral oxygen delivery and consumption, measured by oxygen extraction fraction (OEF), in patients with neuro-PCC.Methods: 25 participants with neuro-PCC (8 previously hospitalized and 17 not hospitalized) and 59 age-matched healthy controls were studied. Global OEF was quantified using TRUST MRI and compared across the three groups. Associations between OEF and neurobehavioral measures were also evaluated in participants with neuro-PCC.Results: OEF was significantly different (one-way ANCOVA-p=0.046) among the three groups, after accounting for age and sex. On post-hoc analyses, previously hospitalized neuro-PCC participants had significantly higher OEF (42.40 ± 5.40 %) than both uninfected controls (37.70 ± 5.09 %, p=0.032) and neuro-PCC participants without hospitalization (37.02 ± 5.05 %, p=0.015). Within the participants with neuro-PCC, OEF was significantly associated with locomotor function assessed with the 4-m walk gait speed score (β=-0.03, r=0.34, p=0.003).Conclusions: Participants with neuro-PCC had altered cerebral OEF, which is also associated with slower locomotion. OEF is a promising marker for studying neuro-PCC.","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":"3 3-4","pages":"169-174"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11823640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434446","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}

引用次数: 0

Oligonucleotide therapeutics for neurodegenerative diseases. 寡核苷酸治疗神经退行性疾病。

NeuroImmune pharmacology and therapeutics Pub Date : 2024-11-18 eCollection Date: 2025-03-01 DOI: 10.1515/nipt-2024-0013

Victor Li, Yunlong Huang

引用次数: 0

Build muscles and protect myelin. 锻炼肌肉，保护髓磷脂。

NeuroImmune pharmacology and therapeutics Pub Date : 2024-10-16 eCollection Date: 2024-09-01 DOI: 10.1515/nipt-2024-0015

Ahana Bose, Kalipada Pahan

{"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":"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.","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}

引用次数: 0

Cannabis use, oral dysbiosis, and neurological disorders 吸食大麻、口腔菌群失调和神经系统疾病

NeuroImmune pharmacology and therapeutics Pub Date : 2024-08-09 DOI: 10.1515/nipt-2024-0012

Amber A. Hazzard, Marice K McCrorey, Tabinda Salman, Douglas E. Johnson, Zhenwu Luo, Xiaoyu Fu, Andrew P. Keegan, Andreana Benitez, Sylvia Fitting, Wei Jiang

引用次数: 0

Biodegradable cannabidiol: a potential nanotherapeutic for neuropathic pain 生物降解大麻二酚：治疗神经性疼痛的潜在纳米疗法

NeuroImmune pharmacology and therapeutics Pub Date : 2024-07-24 DOI: 10.1515/nipt-2024-0008

Sana Qayum, Rebecca R. Schmitt, Janvhi S. Machhar, Sonali Garg, Caroline Bass, V. Muthaiah, Tracey A. Ignatowski, Supriya D. Mahajan

{"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}

引用次数: 0

Something to talk about; crosstalk disruption at the neurovascular unit during HIV infection of the CNS 有话要说；中枢神经系统感染艾滋病毒期间神经血管单元的串联干扰

NeuroImmune pharmacology and therapeutics Pub Date : 2024-07-24 DOI: 10.1515/nipt-2024-0003

Kalpani N U Galpayage Dona, Mohammed M. Benmassaoud, Cassandra D. Gipson, Jay P. McLaughlin, Servio H. Ramirez, Allison M. Andrews

{"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}

引用次数: 0

Sedation with midazolam in the NICU: implications on neurodevelopment 在新生儿重症监护室使用咪达唑仑镇静剂：对神经发育的影响

NeuroImmune pharmacology and therapeutics Pub Date : 2024-07-24 DOI: 10.1515/nipt-2024-0009

Nghi M Nguyen, Gurudutt Pendyala

引用次数: 0