LIVIVO - Search results -

Search results

Result 1 - 10 of total 44

Search options

Article ; Online: Pore-forming neurons: a new paradigm of pyroptotic cell death in HIV-associated neurocognitive disorder.

Periyasamy, Palsamy / Buch, Shilpa

2024 Volume 147, Issue 2, Page(s) 335–336

MeSH term(s)	Humans ; Pyroptosis ; Caspases/metabolism ; Gasdermins ; HIV Infections/complications ; Neurocognitive Disorders ; Neurons/metabolism
Chemical Substances	Caspases (EC 3.4.22.-) ; Gasdermins
Language	English
Publishing date	2024-03-06
Publishing country	England
Document type	Editorial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	80072-7
ISSN	1460-2156 ; 0006-8950
ISSN (online)	1460-2156
ISSN	0006-8950
DOI	10.1093/brain/awad435
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ui II Zs.26: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article: Potential Biomarkers in Experimental Animal Models for Traumatic Brain Injury.

Deshetty, Uma Maheswari / Periyasamy, Palsamy

Journal of clinical medicine

2023 Volume 12, Issue 12

Abstract: Traumatic brain injury (TBI) is a complex and multifaceted disorder that has become a significant public health concern worldwide due to its contribution to mortality and morbidity. This condition encompasses a spectrum of injuries, including axonal ... ...

Abstract	Traumatic brain injury (TBI) is a complex and multifaceted disorder that has become a significant public health concern worldwide due to its contribution to mortality and morbidity. This condition encompasses a spectrum of injuries, including axonal damage, contusions, edema, and hemorrhage. Unfortunately, specific effective therapeutic interventions to improve patient outcomes following TBI are currently lacking. Various experimental animal models have been developed to mimic TBI and evaluate potential therapeutic agents to address this issue. These models are designed to recapitulate different biomarkers and mechanisms involved in TBI. However, due to the heterogeneous nature of clinical TBI, no single experimental animal model can effectively mimic all aspects of human TBI. Accurate emulation of clinical TBI mechanisms is also tricky due to ethical considerations. Therefore, the continued study of TBI mechanisms and biomarkers, of the duration and severity of brain injury, treatment strategies, and animal model optimization is necessary. This review focuses on the pathophysiology of TBI, available experimental TBI animal models, and the range of biomarkers and detection methods for TBI. Overall, this review highlights the need for further research to improve patient outcomes and reduce the global burden of TBI.
Language	English
Publishing date	2023-06-08
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm12123923
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Role of pyroptosis in the pathogenesis of various neurological diseases.

Oladapo, Abiola / Jackson, Thomas / Menolascino, Jueliet / Periyasamy, Palsamy

Brain, behavior, and immunity

2024 Volume 117, Page(s) 428–446

Abstract: Pyroptosis, an inflammatory programmed cell death process, has recently garnered significant attention due to its pivotal role in various neurological diseases. This review delves into the intricate molecular signaling pathways governing pyroptosis, ... ...

Abstract	Pyroptosis, an inflammatory programmed cell death process, has recently garnered significant attention due to its pivotal role in various neurological diseases. This review delves into the intricate molecular signaling pathways governing pyroptosis, encompassing both caspase-1 dependent and caspase-1 independent routes, while emphasizing the critical role played by the inflammasome machinery in initiating cell death. Notably, we explore the Nucleotide-binding domain leucine-rich repeat (NLR) containing protein family, the Absent in melanoma 2-like receptor family, and the Pyrin receptor family as essential activators of pyroptosis. Additionally, we comprehensively examine the Gasdermin family, renowned for their role as executioner proteins in pyroptosis. Central to our review is the interplay between pyroptosis and various central nervous system (CNS) cell types, including astrocytes, microglia, neurons, and the blood-brain barrier (BBB). Pyroptosis emerges as a significant factor in the pathophysiology of each cell type, highlighting its far-reaching impact on neurological diseases. This review also thoroughly addresses the involvement of pyroptosis in specific neurological conditions, such as HIV infection, drug abuse-mediated pathologies, Alzheimer's disease, and Parkinson's disease. These discussions illuminate the intricate connections between pyroptosis, chronic inflammation, and cell death in the development of these disorders. We also conducted a comparative analysis, contrasting pyroptosis with other cell death mechanisms, thereby shedding light on their unique aspects. This approach helps clarify the distinct contributions of pyroptosis to neuroinflammatory processes. In conclusion, this review offers a comprehensive exploration of the role of pyroptosis in various neurological diseases, emphasizing its multifaceted molecular mechanisms within various CNS cell types. By elucidating the link between pyroptosis and chronic inflammation in the context of neurodegenerative disorders and infections, it provides valuable insights into potential therapeutic targets for mitigating these conditions.
MeSH term(s)	Humans ; Pyroptosis ; HIV Infections ; Nervous System Diseases ; Caspase 1 ; Inflammation
Chemical Substances	Caspase 1 (EC 3.4.22.36)
Language	English
Publishing date	2024-02-07
Publishing country	Netherlands
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	639219-2
ISSN	1090-2139 ; 0889-1591
ISSN (online)	1090-2139
ISSN	0889-1591
DOI	10.1016/j.bbi.2024.02.001
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2276: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 327: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Role of the gut-brain axis in HIV and drug abuse-mediated neuroinflammation.

Ray, Sudipta / Sil, Susmita / Kannan, Muthukumar / Periyasamy, Palsamy / Buch, Shilpa

Advances in drug and alcohol research

2023 Volume 3, Page(s) 11092

Abstract: Drug abuse and related disorders are a global public health crisis affecting millions, but to date, limited treatment options are available. Abused drugs include but are not limited to opioids, cocaine, nicotine, methamphetamine, and alcohol. Drug abuse ... ...

Abstract	Drug abuse and related disorders are a global public health crisis affecting millions, but to date, limited treatment options are available. Abused drugs include but are not limited to opioids, cocaine, nicotine, methamphetamine, and alcohol. Drug abuse and human immunodeficiency virus-1/acquired immune deficiency syndrome (HIV-1/AIDS) are inextricably linked. Extensive research has been done to understand the effect of prolonged drug use on neuronal signaling networks and gut microbiota. Recently, there has been rising interest in exploring the interactions between the central nervous system and the gut microbiome. This review summarizes the existing research that points toward the potential role of the gut microbiome in the pathogenesis of HIV-1-linked drug abuse and subsequent neuroinflammation and neurodegenerative disorders. Preclinical data about gut dysbiosis as a consequence of drug abuse in the context of HIV-1 has been discussed in detail, along with its implications in various neurodegenerative disorders. Understanding this interplay will help elucidate the etiology and progression of drug abuse-induced neurodegenerative disorders. This will consequently be beneficial in developing possible interventions and therapeutic options for these drug abuse-related disorders.
Language	English
Publishing date	2023-03-03
Publishing country	Switzerland
Document type	Journal Article ; Review
ISSN	2674-0001
ISSN (online)	2674-0001
DOI	10.3389/adar.2023.11092
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: The Epigenetic Role of miR-124 in HIV-1 Tat- and Cocaine-Mediated Microglial Activation.

Periyasamy, Palsamy / Thangaraj, Annadurai / Kannan, Muthukumar / Oladapo, Abiola / Buch, Shilpa

International journal of molecular sciences

2022 Volume 23, Issue 23

Abstract: HIV-1 and drug abuse have been indissolubly allied as entwined epidemics. It is well-known that drug abuse can hasten the progression of HIV-1 and its consequences, especially in the brain, causing neuroinflammation. This study reports the combined ... ...

Abstract	HIV-1 and drug abuse have been indissolubly allied as entwined epidemics. It is well-known that drug abuse can hasten the progression of HIV-1 and its consequences, especially in the brain, causing neuroinflammation. This study reports the combined effects of HIV-1 Transactivator of Transcription (Tat) protein and cocaine on miR-124 promoter DNA methylation and its role in microglial activation and neuroinflammation. The exposure of mouse primary microglial cells to HIV-1 Tat (25 ng/mL) and/or cocaine (10 μM) resulted in the significantly decreased expression of primary (pri)-miR-124-1, pri-miR-124-2, and mature miR-124 with a concomitant upregulation in DNMT1 expression as well as global DNA methylation. Our bisulfite-converted genomic DNA sequencing also revealed significant promoter DNA methylation in the pri-miR-124-1 and pri-miR-124-2 in HIV-1 Tat- and cocaine-exposed mouse primary microglial cells. We also found the increased expression of proinflammatory cytokines such as IL1β, IL6 and TNF in the mouse primary microglia exposed to HIV-1 Tat and cocaine correlated with microglial activation. Overall, our findings demonstrate that the exposure of mouse primary microglia to both HIV-1 Tat and cocaine could result in intensified microglial activation via the promoter DNA hypermethylation of miR-124, leading to the exacerbated release of proinflammatory cytokines, ultimately culminating in neuroinflammation.
MeSH term(s)	Animals ; Mice ; HIV-1/genetics ; HIV-1/metabolism ; Cocaine/pharmacology ; Cocaine/metabolism ; Trans-Activators/metabolism ; MicroRNAs/metabolism ; tat Gene Products, Human Immunodeficiency Virus/metabolism ; Microglia/metabolism ; Cytokines/metabolism ; Cells, Cultured
Chemical Substances	Cocaine (I5Y540LHVR) ; Trans-Activators ; MicroRNAs ; tat Gene Products, Human Immunodeficiency Virus ; Cytokines ; Mirn124 microRNA, mouse
Language	English
Publishing date	2022-11-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms232315017
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Role of Dysregulated Autophagy in HIV Tat, Cocaine, and cART Mediated NLRP3 Activation in Microglia.

Singh, Seema / Thangaraj, Annadurai / Chivero, Ernest T / Guo, Ming-Lei / Periyasamy, Palsamy / Buch, Shilpa

Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology

2023 Volume 18, Issue 3, Page(s) 327–347

Abstract: Despite the ability of combination antiretroviral therapy (cART) to suppress viremia, there is persistence low levels of HIV proteins such as Transactivator of transcription (Tat) in the central nervous system (CNS), contributing to glial activation and ... ...

Abstract	Despite the ability of combination antiretroviral therapy (cART) to suppress viremia, there is persistence low levels of HIV proteins such as Transactivator of transcription (Tat) in the central nervous system (CNS), contributing to glial activation and neuroinflammation. Accumulating evidence also implicates the role of drugs of abuse in exacerbating neurological complications associated with HIV-1. The combined effects of HIV Tat, drugs of abuse, and cART can thus create a toxic milieu in the CNS. The present study investigated the combinatorial effects of HIV-Tat, cocaine, and cART on autophagy and NLRP3 inflammasome activation. We selected a combination of three commonly used cART regimens: tenofovir, emtricitabine, and dolutegravir. Our results demonstrated that exposure of mouse primary microglia (MPMs) to these agents-HIV Tat (25 ng/ml), cocaine (1 μM), and cART (1 μM each) resulted in upregulation of autophagy markers: Beclin1, LC3B-II, and SQSTM1 with impaired lysosomal functioning involving increased lysosomal pH, decreased LAMP2 and cathepsin D, ultimately leading to dysregulated autophagy. Our findings also demonstrated activation of the NLRP3 signaling in microglia exposed to these agents. We further demonstrated that gene silencing of key autophagy protein BECN1 significantly blocked NLRP3-mediated activation of microglia. Silencing of NLRP3, however, failed to block HIV Tat, cocaine, and cART-mediated dysregulation of the autophagy-lysosomal axis; these in vitro phenomena were also validated in vivo using iTat mice administered cocaine and cART. This study thus underscores the cooperative effects of HIV Tat, cocaine, and cART in exacerbating microglial activation involving dysregulated autophagy and activation of the NLRP3 inflammasome signaling.
MeSH term(s)	Mice ; Animals ; Microglia ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Cocaine/pharmacology ; Inflammasomes/metabolism ; Trans-Activators/metabolism ; Trans-Activators/pharmacology ; Autophagy ; tat Gene Products, Human Immunodeficiency Virus/metabolism ; HIV Infections/metabolism
Chemical Substances	NLR Family, Pyrin Domain-Containing 3 Protein ; Cocaine (I5Y540LHVR) ; Inflammasomes ; Trans-Activators ; tat Gene Products, Human Immunodeficiency Virus
Language	English
Publishing date	2023-05-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2227405-4
ISSN	1557-1904 ; 1557-1890
ISSN (online)	1557-1904
ISSN	1557-1890
DOI	10.1007/s11481-023-10063-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

Order via subito

Details ▾
- Full text online
- Order with fees

Article ; Online: Opioid abuse and SIV infection in non-human primates.

Deshetty, Uma Maheswari / Ray, Sudipta / Singh, Seema / Buch, Shilpa / Periyasamy, Palsamy

Journal of neurovirology

2023 Volume 29, Issue 4, Page(s) 377–388

Abstract: Human immunodeficiency virus (HIV) and drug abuse are intertwined epidemics, leading to compromised adherence to combined antiretroviral therapy (cART) and exacerbation of NeuroHIV. As opioid abuse causes increased viral replication and load, leading to ... ...

Abstract	Human immunodeficiency virus (HIV) and drug abuse are intertwined epidemics, leading to compromised adherence to combined antiretroviral therapy (cART) and exacerbation of NeuroHIV. As opioid abuse causes increased viral replication and load, leading to a further compromised immune system in people living with HIV (PLWH), it is paramount to address this comorbidity to reduce the NeuroHIV pathogenesis. Non-human primates are well-suited models to study mechanisms involved in HIV neuropathogenesis and provide a better understanding of the underlying mechanisms involved in the comorbidity of HIV and drug abuse, leading to the development of more effective treatments for PLWH. Additionally, using broader behavioral tests in these models can mimic mild NeuroHIV and aid in studying other neurocognitive diseases without encephalitis. The simian immunodeficiency virus (SIV)-infected rhesus macaque model is instrumental in studying the effects of opioid abuse on PLWH due to its similarity to HIV infection. The review highlights the importance of using non-human primate models to study the comorbidity of opioid abuse and HIV infection. It also emphasizes the need to consider modifiable risk factors such as gut homeostasis and pulmonary pathogenesis associated with SIV infection and opioid abuse in this model. Moreover, the review suggests that these non-human primate models can also be used in developing effective treatment strategies for NeuroHIV and opioid addiction. Therefore, non-human primate models can significantly contribute to understanding the complex interplay between HIV infection, opioid abuse, and associated comorbidities.
MeSH term(s)	Animals ; Humans ; HIV Infections/drug therapy ; Simian Acquired Immunodeficiency Syndrome ; Macaca mulatta ; Simian Immunodeficiency Virus ; HIV ; Opioid-Related Disorders ; Viral Load
Language	English
Publishing date	2023-07-07
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	1283265-0
ISSN	1538-2443 ; 1355-0284
ISSN (online)	1538-2443
ISSN	1355-0284
DOI	10.1007/s13365-023-01153-z
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 4426: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: HIV-1 Tat-mediated microglial ferroptosis involves the miR-204-ACSL4 signaling axis.

Kannan, Muthukumar / Sil, Susmita / Oladapo, Abiola / Thangaraj, Annadurai / Periyasamy, Palsamy / Buch, Shilpa

Redox biology

2023 Volume 62, Page(s) 102689

Abstract: This study was focused on exploring the role of the HIV-1 Tat protein in mediating microglial ferroptosis. Exposure of mouse primary microglial cells (mPMs) to HIV-1 Tat protein resulted in induction of ferroptosis, which was characterized by increased ... ...

Abstract	This study was focused on exploring the role of the HIV-1 Tat protein in mediating microglial ferroptosis. Exposure of mouse primary microglial cells (mPMs) to HIV-1 Tat protein resulted in induction of ferroptosis, which was characterized by increased expression of Acyl-CoA synthetase long-chain family member 4 (ACSL4), in turn, leading to increased generation of oxidized phosphatidylethanolamine, elevated levels of lipid peroxidation, upregulated labile iron pool (LIP) and ferritin heavy chain-1 (FTH1), decreased glutathione peroxidase-4 and mitochondrial outer membrane rupture. Also, inhibition of ferroptosis by ferrostatin-1 (Fer-1) or deferoxamine (DFO) treatment suppressed ferroptosis-related changes in mPMs. Similarly, the knockdown of ACSL4 by gene silencing also inhibited ferroptosis induced by HIV-1 Tat. Furthermore, increased lipid peroxidation resulted in increased release of proinflammatory cytokines, such as TNFα, IL6, and IL1β and microglial activation. Pretreatment of mPMs with Fer-1 or DFO further blocked HIV-1 Tat-mediated microglial activation in vitro and reduced the expression and release of proinflammatory cytokines. We identified miR-204 as an upstream modulator of ACSL4, which was downregulated in mPMs exposed to HIV-1 Tat. Transient transfection of mPMs with miR-204 mimics reduced the expression of ACSL4 while inhibiting HIV-1 Tat-mediated ferroptosis and the release of proinflammatory cytokines. These in vitro findings were further validated in HIV-1 transgenic rats as well as HIV + ve human brain samples. Overall, this study underscores a novel mechanism(s) underlying HIV-1 Tat-mediated ferroptosis and microglial activation involving miR-204-ACSL4 signaling.
MeSH term(s)	Animals ; Humans ; Mice ; Rats ; Coenzyme A Ligases ; Cytokines/metabolism ; Ferroptosis ; Gene Products, tat/metabolism ; HIV-1/genetics ; Microglia/metabolism ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Rats, Transgenic
Chemical Substances	Acsl4 protein, mouse (EC 6.2.1.-) ; Coenzyme A Ligases (EC 6.2.1.-) ; Cytokines ; Gene Products, tat ; MicroRNAs ; MIRN204 microRNA, human ; MIRN204 microRNA, rat
Language	English
Publishing date	2023-04-01
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2701011-9
ISSN	2213-2317 ; 2213-2317
ISSN (online)	2213-2317
ISSN	2213-2317
DOI	10.1016/j.redox.2023.102689
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Age-related cataracts: Role of unfolded protein response, Ca

Periyasamy, Palsamy / Shinohara, Toshimichi

Progress in retinal and eye research

2017 Volume 60, Page(s) 1–19

Abstract: Age-related cataracts are closely associated with lens chronological aging, oxidation, calcium imbalance, hydration and crystallin modifications. Accumulating evidence indicates that misfolded proteins are generated in the endoplasmic reticulum (ER) by ... ...

Abstract	Age-related cataracts are closely associated with lens chronological aging, oxidation, calcium imbalance, hydration and crystallin modifications. Accumulating evidence indicates that misfolded proteins are generated in the endoplasmic reticulum (ER) by most cataractogenic stresses. To eliminate misfolded proteins from cells before they can induce senescence, the cells activate a clean-up machinery called the ER stress/unfolded protein response (UPR). The UPR also activates the nuclear factor-erythroid-2-related factor 2 (Nrf2), a central transcriptional factor for cytoprotection against stress. Nrf2 activates nearly 600 cytoprotective target genes. However, if ER stress reaches critically high levels, the UPR activates destructive outputs to trigger programmed cell death. The UPR activates mobilization of ER-Ca
MeSH term(s)	Calcium/metabolism ; Cataract/metabolism ; Cataract/physiopathology ; Cytoprotection/physiology ; Endoplasmic Reticulum Stress/physiology ; Epigenesis, Genetic/physiology ; Humans ; Kelch-Like ECH-Associated Protein 1/physiology ; Lens, Crystalline/metabolism ; Lens, Crystalline/physiopathology ; NF-E2-Related Factor 2/physiology ; Reactive Oxygen Species/metabolism ; Unfolded Protein Response/physiology
Chemical Substances	Kelch-Like ECH-Associated Protein 1 ; NF-E2-Related Factor 2 ; NFE2L2 protein, human ; Reactive Oxygen Species ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2017-08-31
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	1182683-6
ISSN	1873-1635 ; 1350-9462
ISSN (online)	1873-1635
ISSN	1350-9462
DOI	10.1016/j.preteyeres.2017.08.003
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Se 824: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: NLRP3 Inflammasome Blockade Reduces Cocaine-Induced Microglial Activation and Neuroinflammation.

Chivero, Ernest T / Thangaraj, Annadurai / Tripathi, Ashutosh / Periyasamy, Palsamy / Guo, Ming-Lei / Buch, Shilpa

Molecular neurobiology

2021 Volume 58, Issue 5, Page(s) 2215–2230

Abstract: Cocaine use disorder is a major health crisis that is associated with increased oxidative stress and neuroinflammation. While the role of NLRP3 inflammasome in mediating neuroinflammation is well-recognized, whether cocaine induces this response remains ... ...

Abstract	Cocaine use disorder is a major health crisis that is associated with increased oxidative stress and neuroinflammation. While the role of NLRP3 inflammasome in mediating neuroinflammation is well-recognized, whether cocaine induces this response remains unexplored. Based on the premise that cocaine induces both reactive oxygen species (ROS) as well as microglial activation, we hypothesized that cocaine-mediated microglial activation involves both ROS and NLRP3 signaling pathways. We examined activation of the NLRP3 pathway in microglia exposed to cocaine, followed by validation in mice administered either cocaine or saline for 7 days, with or without pretreatment with the NLRP3 inhibitor, MCC950, and in postmortem cortical brain tissues of chronic cocaine-dependent humans. We found that microglia exposed to cocaine exhibited significant induction of NLRP3 and mature IL-1β expression. Intriguingly, blockade of ROS (Tempol) attenuated cocaine-mediated priming of NLRP3 and microglial activation (CD11b). Blockade of NLRP3 by both pharmacological (MCC950) as well as gene silencing (siNLRP3) approaches underpinned the critical role of NLRP3 in cocaine-mediated activation of inflammasome and microglial activation. Pretreatment of mice with MCC950 followed by cocaine administration for 7 days mitigated cocaine-mediated upregulation of mature IL-1β and CD11b, in both the striatum and the cortical regions. Furthermore, cortical brain tissues of chronic cocaine-dependent humans also exhibited upregulated expression of the NLRP3 pathway mediators compared with non-cocaine dependent controls. Collectively, these findings suggest that cocaine activates microglia involving the NLRP3 inflammasome pathway, thereby contributing to neuroinflammation. NLRP3 can thus be considered as a potential therapeutic target for alleviating cocaine-mediated neuroinflammation.
MeSH term(s)	Animals ; Caspase 1/metabolism ; Cell Line ; Cocaine/pharmacology ; Dopamine Uptake Inhibitors/pharmacology ; Frontal Lobe/drug effects ; Frontal Lobe/metabolism ; Humans ; Inflammasomes/drug effects ; Inflammasomes/metabolism ; Interleukin-1beta/metabolism ; Mice ; Microglia/drug effects ; Microglia/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
Chemical Substances	Dopamine Uptake Inhibitors ; Inflammasomes ; Interleukin-1beta ; NLR Family, Pyrin Domain-Containing 3 Protein ; Caspase 1 (EC 3.4.22.36) ; Cocaine (I5Y540LHVR)
Language	English
Publishing date	2021-01-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	645020-9
ISSN	1559-1182 ; 0893-7648
ISSN (online)	1559-1182
ISSN	0893-7648
DOI	10.1007/s12035-020-02184-x
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 2411: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito