Neuropeptides最新文献

Objective

In this study, we explored the neuroprotective effect of melittin (MEL) after brain ischemia using a rat model.

Methods

The rats underwent middle cerebral artery occlusion (MCAO) for 60 min and were randomly divided into the control group, saline group, and MEL group. Rats in each group were injected intraperitoneally with MEL one day before MCAO until sacrificed. Morris water maze and rotation test were used to assess locomotor function and cognitive ability. The 9.4 Tesla MRI was used to scan and assess the infarct volume of the rat brains. Immunohistochemistry was used to detect the sites of action of MEL on microglia. Western blot and ELISA were used to measure the effect of MEL on the production of pro-inflammatory cytokines. The effect of MEL on neuronal cell apoptosis was observed by flow cytometry.

Results

Compared with the saline group, MEL treatment significantly increased the density of neurons in the cerebral cortical and reduced the cerebral infarct size after MCAO (33.9 ± 8.8% vs. 15.8 ± 3.9%, P < 0.05). Meanwhile, the time for MEL-treated rats to complete the water maze task on the 11th day after MCAO was significantly shorter than that of rats in the saline group (P < 0.05). MEL treatment also prolonged the rotarod retention time on day 14 after MCAO. Immunohistochemistry analysis showed that MEL inhibited the activation of microglia and suppressed the expression of TNF-α, IL-6, and IL-1β in the brain after ischemia. MEL treatment resulted in a significant decrease in TLR4, MyD88, and NF-κB p65 levels in extracts from the ischemic cerebral cortex. Finally, MEL reduced neuronal apoptosis induced by ischemic stroke (P < 0.05).

Conclusion

MEL treatment promotes neurological function recovery after cerebral ischemia in rats. These effects are potentially mediated through anti-inflammatory and anti-apoptotic mechanisms.

The molecular mechanisms underlying neuronal leptin and insulin resistance in obesity and diabetes are not fully understood. In this study, we show that induction of the unfolded protein response transcription factor, spliced X-box binding protein 1 (Xbp1s), in Agouti-Related Peptide (AgRP) neurons alone, is sufficient to not only protect against but also significantly reverse diet-induced obesity (DIO) as well as improve leptin and insulin sensitivity, despite activation of endoplasmic reticulum stress. We also demonstrate that constitutive expression of Xbp1s in AgRP neurons contributes to improved insulin sensitivity and glucose tolerance. Together, our results identify critical molecular mechanisms linking ER stress in arcuate AgRP neurons to acute leptin and insulin resistance as well as liver glucose metabolism in DIO and diabetes.

High ambient temperatures (HT) can increase diencephalic neuropeptide Y (NPY) expression, and central injection of NPY attenuates heat stress responses while inducing an antioxidative state in the chick spleen. However, there is a lack of knowledge about NPY receptor expression, and its regulation by HT, in the chick spleen. In the current study, male chicks were used to measure the expression of NPY receptors in the spleen and other immune organs under acute (30 vs. 40 ± 1°C for 3 h) or chronic (30 vs. 40 ± 1°C for 3 h/day for 3 days) exposure to HT and in response to central injection of NPY (47 pmol, 188 pmol, or 1 nmol). We found that NPY-Y4 receptor mRNA was expressed in the spleen, but not in other immune organs studied. Immunofluorescence staining revealed that NPY-Y4 receptors were localized in the splenic pulp. Furthermore, NPY-Y4 receptor mRNA increased in the chick spleen under both acute and chronic exposure to HT. Central NPY at two dose levels (47 and 188 pmol) and a higher dose (1 nmol) did not increase splenic NPY-Y4 receptor mRNA expression or splenic epinephrine under HT (35 ± 1°C), and significantly increased 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations under HT (40 ± 1°C). In conclusion, increased expression of NPY-Y4 receptor mRNA in the spleen under HT suggest that Y4 receptor may play physiological roles in response to HT in male chicks.

The destruction of the blood-brain barrier and damage to the gastrointestinal mucosa after intracerebral hemorrhage (ICH) are important reasons for its high disability and mortality rates. However, the exact etiology is not yet clear. In addition, there are currently no effective treatments for improving cerebral edema and gastric mucosal damage after ICH. Trefoil factor 1 (TFF1) is a secretory protein that plays a crucial role in maintaining the integrity and barrier function of the gastric mucosa, and it has been reported to have a protective effect on brain damage induced by various causes. This study utilized a rat model of ICH induced by type IV collagenase was utilized, and intervened with recombinant TFF1 protein from an external institute to investigate the protective mechanisms of TFF1 against brain edema and gastric mucosal damage after ICH. The results demonstrated that TFF1 alleviated the neurological function and gastric mucosal damage in the rat model of ICH induced by type IV collagenase. TFF1 may ensure the integrity of the blood-brain and gastric mucosal barriers by regulating the EGFR (epidermal growth factor receptor)/Src (non-receptor tyrosine kinase)/FAK (focal adhesion kinase) pathway. Clearly, the disruption of the blood-brain barrier and the destruction of the gastric mucosal barrier are key pathological features of ICH, and TFF1 can improve the progression of blood-brain barrier and gastric mucosal barrier disruption in ICH by regulating the EGFR/Src/FAK pathway. Therefore, TFF1 may be a potential target for the treatment of ICH.

Chronic pain induced by pathological insults to the sensorimotor system is a typical form of neuropathic pain (NP), and the underlying mechanism is complex. Currently, there are no successful therapeutic interventions for NP. Orexin B is a neuropeptide with a wide range of biological functions. However, the pharmacological function of orexin B in chronic neuropathic pain has been less studied. Here, we aim to examine the neuroprotective effects of orexin B in chronic constriction injury (CCI)- induced NP. Firstly, we found that orexin type 2 receptor (OX2R) but not orexin type 1 receptor (OX1R) was reduced in the spinal cord (SC) of CCI-treated rats. Mechanical withdrawal threshold and thermal withdrawal latency assays display that administration of orexin B clearly ameliorated CCI-evoked neuropathic pain dose-dependently. Notably, orexin B treatment also effectively prevented microglia activation by reducing the levels of IBA1. Additionally, orexin B was also found to suppress the inflammatory response in the SC tissue by reducing the levels of IL-6, TNF-α, iNOS, and COX-2 as well as the production of NO and PGE₂ in CCI-treated rats. Furthermore, orexin B administration attenuated oxidative stress (OS) by increasing the activity of SOD and the levels of GSH. Mechanically, orexin B prevented activation of JNK/NF-κB signaling in the SC of CCI-treated rats. Based on these findings, we conclude that orexin B might have a promising role in ameliorating CCI-evoked neuropathic pain through the inhibition of microglial activation and inflammatory response.

Prokineticin 2 (PK2) binds to prokineticin receptor 1 and prokineticin receptor 2 (PKR1 and PKR2, respectively), two G protein-coupled receptors (GPCRs) that can mediate multiple signalling pathways by promoting the elevation of intracellular calcium and cAMP levels, phosphorylation of Akt and activation of ERK and STAT3. This work aims to evidence the conservation of protein sequence and the mechanism of PK2 binding to PKR1 to use the zebrafish model for the identification of new drugs as targets of prokineticin receptors. To this end, we first demonstrated that the zebrafish genes pk2 and pkr1 are phylogenetically related to orthologous mammalian genes by constructing evolutionary trees and performing syntenic analyses. Subsequently, by comparing the amino acid sequences, we showed that the interaction sites with PK2 are conserved in the zPKR1. Using GST pull-down and cross-linking experiments, we demonstrated the crucial role of the N-terminal region of zPKR1 for binding to the PK2. Finally, by expressing zPKR1 in CHO cells, we demonstrated the ability of zPKR1 to induce the activation of ERK and STAT3.

Neurodegenerative diseases are the main causes of death and morbidity among elderly people worldwide. From the pathological point of view, oxidative stress, neuroinflammation, mitochondrial damage and apoptosis are the causes of neuronal diseases, and play a harmful role in the process of neuronal cell death and neurodegeneration. The most common neurodegenerative diseases are Alzheimer's disease(AD) and Parkinson's disease(PD), and there is no effective treatment. The physiological role of active peptides in the human body is significant. Modern medical research has found that animal and plant peptides, natural peptides in human body, can act on the central nervous system, and their active components can improve learning and memory ability, and play the roles of antioxidation, anti-inflammation, anti-apoptosis and maintaining the structure and function of mitochondria. This review reviews the reports on neurodegenerative diseases such as AD and PD by active peptides from animals and plants and natural peptides from the human body, and summarizes the neuroprotective mechanism of peptides. A theoretical basis for further research and development of active peptides was provided by examining the research and application of peptides, which provided a theoretical basis for further research and development.

Bromelain is a plant-based molecule with antioxidant, antithrombotic, anticancer, and anti-inflammatory properties. Bromelain has been shown to reduce the release of inflammatory cytokines. This study aimed to determine whether bromelain can prevent ataxia in rats caused by 3-acetylpyridine (3-AP). Thirty-six albino rats were divided into the control, 3-AP, and 3-AP + Brom groups. In the 3-AP + Brom group, bromelain was injected intraperitoneally at 40 mg/kg daily for 30 days. Various techniques such as rotarod, electromyography (EMG), elevated plus maze, IHC, and Sholl analysis were used to evaluate the possible effects of bromelain on cerebellar neurons and glial cells. The results demonstrated significant improvements in most of the 3-AP + Brom, including motor coordination, neuromuscular response, anxiety, oxidative capacity, microgliosis, astrogliosis, cell death, and morphological variables compared to the 3-AP group. The mechanism of action of bromelain in restoring cerebellar ataxia needs further investigation, but it may be a candidate to help restore degeneration in animals with ataxia.

Neuropeptide Y (NPY) plays a crucial role in controlling energy homeostasis and feeding behaviour. The role of NPY neurons located in the arcuate nucleus of the hypothalamus (Arc) in responding to homeostatic signals has been the focus of much investigation, but most studies have used AgRP promoter-driven models, which do not fully encompass Arc NPY neurons. To directly investigate NPY-expressing versus AgRP-expressing Arc neurons function, we utilised chemogenetic techniques in NPY-Cre and AgRP-Cre animals to activate Arc NPY or AgRP neurons in the presence of food and food-related stimuli. Our findings suggest that chemogenetic activation of the broader population of Arc NPY neurons, including AgRP-positive and AgRP-negative NPY neurons, has equivalent effects on feeding behaviour as activation of Arc AgRP neurons. Our results demonstrate that these Arc NPY neurons respond specifically to caloric signals and do not respond to non-caloric signals, in line with what has been observed in AgRP neurons. Activating Arc NPY neurons significantly increases food consumption and influences macronutrient selection to prefer fat intake.

Introduction

This study explored how acute sleep deprivation (ASD) before myocardial ischemia influences oxytocin release from paraventricular (PVN) neurons and its correlation with sympathetic nervous system (SNS) activity post-acute sleep loss, impacting subsequent left ventricular (LV) remodeling following myocardial infarction (MI).

Methods

The study was conducted in two phases: induction of ASD, inducing MI, blood sampling, euthanizing animals and collecting their heart and brain for histological and gene expression evaluations. The animals in first and second phase were euthanized 24 h and 14 days after MI, respectively.

Results

Pre-MI ASD, accompanied by increased serum epinephrine levels within 24 h of MI, upregulated oxytocin and cFos expression in the PVN. Also, pre-MI ASD resulted in decreased serum PAB levels 14 days post-MI (P < 0.001). While notable echocardiographic changes were seen in MI versus sham groups, ASD demonstrated protective effects. This was evidenced by reduced infarct size, elevated TIMP1, MMP2, and MMP9 in the LV of SD + MI animals versus MI alone (P < 0.05). Additionally, histological analysis showed reduced LV fibrosis in pre-MI ASD subjects (P < 0.05).

Conclusion

Our study supports the notion that activation of oxytocin neurons within the PVN subsequent to ASD interacts with autonomic centers in the central nervous system. This enhanced sympathetic outflow to the heart prior to MI triggers a preconditioning response, thereby mediating cardioprotection through decreased oxidative stress biomarkers and regulated extracellular matrix (ECM) turnover.