Dataset Information

Albiflorin Attenuates Mood Disorders Under Neuropathic Pain State by Suppressing the Hippocampal NLRP3 Inflammasome Activation During Chronic Constriction Injury.

ABSTRACT:

Background

Neuropathic pain is a multifaceted and ubiquitous disease across the globe. Mood disorders, such as anxiety and depression, are frequently observed in patients suffering from neuropathic pain. Both neuropathic pain and comorbid mood disorders seriously impact quality of life. Accumulated evidence shows that activation of the NOD-like receptor protein 3 (NLRP3) inflammasome is involved in the neuroinflammatory pathogenesis of neuropathic pain, anxiety, and depression. However, the role of the NLRP3 inflammasome in the pathological process of anxiety and depression under the neuropathic pain state has not been fully described. Albiflorin, a monoterpene glycoside, may be a potential regulator of the NLRP3 inflammasome, but it is not clear whether albiflorin relates to NLRP3 inflammasome activation.

Methods

We used a systematic pharmacological method to confirm whether the activation of the NLRP3 inflammasome in the hippocampus was involved in the development of neuropathic pain associated with mood disorders and whether albiflorin could be an effective treatment for these symptoms.

Results

The NLRP3 inflammasome contributed to the neuropathic pain and comorbid anxiety and depression-like behaviors induced by chronic constriction injury of the sciatic nerve, and albiflorin may relieve these symptoms via inhibition of the NLRP3 inflammasome activity. Moreover, albiflorin enhanced the translocation of the nuclear factor erythroid 2-related factor 2 into the nucleus and suppressed nuclear factor-kappa B activity in the hippocampus.

Conclusions

Albiflorin, as a potential therapeutic agent, might greatly improve the overall symptoms of neuropathic pain.

SUBMITTER: Liu P

PROVIDER: S-EPMC7816674 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Albiflorin Attenuates Mood Disorders Under Neuropathic Pain State by Suppressing the Hippocampal NLRP3 Inflammasome Activation During Chronic Constriction Injury.

Liu Pei P Chen Jianjun J Ma Shuai S Zhang Jianjun J Zhou Jianyu J

The international journal of neuropsychopharmacology 20210101 1

<h4>Background</h4>Neuropathic pain is a multifaceted and ubiquitous disease across the globe. Mood disorders, such as anxiety and depression, are frequently observed in patients suffering from neuropathic pain. Both neuropathic pain and comorbid mood disorders seriously impact quality of life. Accumulated evidence shows that activation of the NOD-like receptor protein 3 (NLRP3) inflammasome is involved in the neuroinflammatory pathogenesis of neuropathic pain, anxiety, and depression. However, ...[more]

PMID: 33000169

Similar Datasets

Project description:Background Paclitaxel is commonly used as a cancer chemotherapy drug that frequently causes peripheral neuropathic pain. Inflammasome is a multiprotein complex consisting of Nod-like receptor proteins (NLRPs), apoptosis-associated speck-like protein, and caspase-1, which functions to switch on the inflammatory process and the release of interleukin-1?. Growing evidences have supported that peripheral interleukin-1? is critical in enhancing paclitaxel-induced neuropathic pain. However, whether activation of NLRP3 inflammasome in peripheral nerve contributes to paclitaxel-induced neuropathic pain is still unclear. Results Paclitaxel induced mechanical allodynia of rats from day 3 and worsened gradually till 3 weeks after injection. Paclitaxel resulted in expression of NLRP3 and activated fragments of caspase-1 and interleukin-1? in L4-6 dorsal root ganglia and sciatic nerve three weeks after injection, indicating activation of NLRP3 inflammasome. The expression of NLRP3 was located in CD68-labeled macrophages infiltrating in L4-6 dorsal root ganglia and sciatic nerve, and paclitaxel increased the expression of NLRP3 in macrophage. Moreover, the paclitaxel elicited mitochondria damage, which became swollen and enlarged in macrophages and axons of sciatic nerve three weeks after injection. In vitro, paclitaxel increased the number of damaged mitochondria and mitochondrial reactive oxygen species production in the rat alveolar macrophage cell line NR8383. The administration of a non-specific reactive oxygen species scavenger, phenyl-N-tert-butylnitrone, markedly alleviated mechanical allodynia and inhibited the activation of NLRP3 inflammasome in L4-6 dorsal root ganglia and sciatic nerve of the paclitaxel-induced neuropathic pain model. Conclusions Paclitaxel induced mechanical allodynia and activation of NLRP3 inflammasome in infiltrated macrophages of L4-6 dorsal root ganglia and sciatic nerve. Paclitaxel elicited mitochondria damage and reactive oxygen species production may result in activation of NLRP3 inflammasome in peripheral nerve, which contributes to paclitaxel-induced neuropathic pain.

Project description:Traumatic brain injury (TBI) remains a major cause of morbidity and disability worldwide and a healthcare burden. TBI is an important risk factor for neurodegenerative diseases hallmarked by exacerbated neuroinflammation. Neuroinflammation in the cerebral cortex plays a critical role in secondary injury progression following TBI. The NOD-like receptors (NLR) family pyrin domain containing 3 (NLRP3) inflammasome is a key player in initiating the inflammatory response in various central nervous system disorders entailing TBI. This current study aims to investigate the role of NLRP3 in repetitive mild traumatic brain injury (rmTBI) and identify the potential neuroprotective effect of saffron extract in regulating the NLRP3 inflammasome. 24 hours following the final injury, rmTBI causes an upregulation in mRNA levels of NLRP3, caspase-1, the apoptosis-associated speck-like protein containing a CARD (ASC), nuclear factor kappa B (NF-κB), interleukin-1Beta (IL-1β), interleukin 18 (IL-18), nuclear factor erythroid 2-related factor 2 (NRF2) and heme oxygenase 1 (HMOX1). Protein levels of NLRP3, sirtuin 1 (SIRT1), glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule 1 (Iba1), and neuronal nuclei (Neu N) also increased after rmTBI. Administration of saffron alleviated the degree of TBI, as evidenced by reducing the neuronal damage, astrocyte, and microglial activation. Pretreatment with saffron inhibited the activation of NLRP3, caspase-1, and ASC concurrent to reduced production of the inflammatory cytokines IL-1β and IL-18. Additionally, saffron extract enhanced SIRT1 expression, NRF2, and HMOX1 upregulation. These results suggest that NLRP3 inflammasome activation and the subsequent inflammatory response in the mice cortex are involved in the process of rmTBI. Saffron blocked the inflammatory response and relieved TBI by activating detoxifying genes and inhibiting NLRP3 activation. The effect of saffron on the NLRP3 inflammasome may be SIRT1 and NF-κB dependent in the rmTBI model. Thus, brain injury biomarkers will help in identifying a potential therapeutic target in treating TBI-induced neurodegenerative diseases.

Dataset Information

Albiflorin Attenuates Mood Disorders Under Neuropathic Pain State by Suppressing the Hippocampal NLRP3 Inflammasome Activation During Chronic Constriction Injury.

Background

Methods

Results

Conclusions

Publications

Albiflorin Attenuates Mood Disorders Under Neuropathic Pain State by Suppressing the Hippocampal NLRP3 Inflammasome Activation During Chronic Constriction Injury.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure