Acta neurobiologiae experimentalis最新文献

Neurodegenerative disorders (NDD) are chronic neurological diseases characterized by loss and/or damage to neurons along with the myelin sheath, and patients are at higher risk of severe infection with the SARS‑CoV‑2. A comprehensive literature search was performed using relevant terms and inclusion‑exclusion criteria. Recent articles, subjects older than 50 years, and articles written in the English language were included, whereas letters to the editor and articles related to pregnant women were excluded from the review study. COVID‑19 appears to damage angiotensin‑II receptors which cause natural killer cells to lose the ability to clear virus‑infected cells, owing to worse outcomes in patients with NDD. COVID‑19 can worsen the symptoms of Alzheimer's disease. In addition, COVID‑19 worsens drug‑responsive motor symptoms in Parkinson's disease (PD) and other symptoms like fatigue and urinary complaints. Vitamin D is essential in decreasing pro‑inflammatory and increasing anti‑inflammatory cytokines in ongoing COVID‑19 infections and reducing angiotensin receptors and, hence, decreasing COVID‑19 infection severity. Telemedicine shows promise for patients with NDD but is yet to overcome legal issues and personal barriers. COVID‑19 has a significant effect on neurodegenerative conditions, which appears partly to the nature of the NDD and the neuro‑invasive capabilities of the SARS‑CoV‑2. The protective role of vitamin D in patients with NDD further supports this hypothesis. Modifications in current health care, like the telemedicine platform, are required to address the increased risk of serious infection in this population. Further studies will be required to clarify conflicting reports in many fields.

Cobalt is a trace element that increases lipid peroxidation and malondialdehyde levels and reduces the antioxidant defense mechanisms of nerve cells. High levels of cobalt exposure may cause peripheral neuropathy, but the mechanism behind this has not yet been elucidated. Taxifolin is a flavonoid whose antioxidant and anti‑inflammatory properties are well‑known. We aimed to investigate the effect of taxifolin on cobalt‑induced oxidative sciatic nerve damage. Eighteen albino male Wistar rats were assigned to three groups: Control, Cobalt, and Taxifolin + Cobalt groups. Total oxidant and total antioxidant status and levels of malondialdehyde, total glutathione, and superoxide dismutase were measured to determine the effect of taxifolin on cobalt‑induced sciatic nerve injury. The following statistically significant effect of taxifolin was observed: It prevented cobalt‑induced oxidative sciatic nerve damage by reducing malondialdehyde levels and total oxidant status and increasing total antioxidant status, total glutathione levels, and superoxide dismutase levels. In a histopathological analysis, we observed similar findings in Control and Taxifolin + Cobalt groups. We determined that taxifolin is effective in preventing cobalt‑induced oxidative damage in sciatic nerve injury.

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease, associated with a decreased cognitive function and severe behavioral abnormalities. This study aimed to explore mechanisms of development and progression of AD. Comprehensive analysis of GSE16759 was performed to identify the differentially expressed lncRNAs (DElncRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs). The differentially expressed RNAs (DERs) were used for the subsequent analysis, including module genes analysis, pathway enrichment analysis, and interaction network analysis. Finally, an AD‑associated network consisting of lncRNA‑miRNA‑mRNA‑pathway was constructed. A total of 431 DEmRNAs, 35 DElncRNAs, and 103 DEmiRNAs between the AD group and the normal control group were identified. DEmRNAs were significantly enriched in 13 pathways, such as focal adhesion, endocytosis, and mTOR signaling pathway. Three modules significantly related to AD were finally screened. The AD‑associated network was constructed, including 2 lncRNAs (A2M‑AS1 and ZNF571‑AS1), 1 miRNA (hsa‑miR‑206), 2 mRNAs (NOTCH3 and JAG1), and 2 pathways (notch signaling pathway and endocrine resistance). A2M‑AS1, ZNF571‑AS1, hsa‑miR‑206, NOTCH3 and JAG1 may be involved in the mechanisms of AD through notch signaling pathway and endocrine resistance.

This study was designed to investigate the involvement of opioidergic/nitrergic systems in the anticonvulsant effect of mefloquine, compared with chloroquine, in mice. Seizures were induced by pentylenetetrazol and maximal electroshock. Mice were randomly subjected to receive mefloquine or chloroquine thirty minutes in advance. The role of opioidergic/nitrergic systems was shown by co‑administration of pharmacological intervention and nitrite levels measurement in mice hippocampi. Results indicated that mefloquine (40 mg/kg) and chloroquine (5 mg/kg) significantly decreased the occurrence of tonic hindlimb extension. Also, mefloquine 120 mg/kg and chloroquine 5 mg/kg significantly increased seizure latency and decreased mortality rate. Mefloquine decreased seizure frequency too. Besides, mefloquine (20 mg/kg) and chloroquine (5, 10 mg/kg) significantly increased seizure threshold. Interestingly, L‑NAME, 7‑NI and naltrexone pre‑treatment reversed the anticonvulsant effects of both mefloquine (20 mg/kg) and chloroquine (5 mg/kg). Moreover, co‑administration of minimal‑effective doses of morphine with mefloquine/chloroquine (both 1 mg/kg) potentiated anticonvulsant effects, which was reversed by naltrexone and endorsed the involvement of opioid receptors. Also, nitrite levels in mice hippocampi remarkably increased after treatment with both mefloquine (20 mg/kg) and chloroquine (5 mg/kg). To conclude, mefloquine could protect the central nervous system against seizures in PTZ/MES‑induced models through opioidergic/nitrergic pathways, with similarity to chloroquine effects.

Caffeine is a psychoactive compound used widely to enhance cognitive functions in human or animal studies. The present study examined the effects of caffeine on cognitive performance and inflammatory factors in mice with medial prefrontal cortex (mPFC) ischemia. Mice underwent a photothrombotic mPFC ischemic stroke and were treated with normal saline or caffeine at different doses intranasally for 7 days. The sham surgery animals received normal saline intranasally. The Morris water maze test and social interaction test were performed to assess spatial and social memories, respectively. In addition, the levels of inflammatory proteins, including tumor necrosis factor‑alpha, interleukin‑6, and interleukin‑10, were measured in the mPFC using immunoblotting. The results showed that mPFC ischemia impaired spatial memory and social behaviors, and caffeine at doses of 0.05 and 0.1 mg improved behavioral outcomes in the ischemic groups. Also, caffeine reversed ischemia‑induced high levels of pro‑inflammatory biomarkers and enhanced the expression of the anti‑inflammatory mediator. Our findings indicate that caffeine alleviated mPFC ischemia‑induced memory disturbances, probably through the modulation of the inflammatory mediators.

Sleep disorder is a puzzling and complex health problem, and sleep deprivation (SD) may be a window for studying sleep disorder. Guipi decoction (GPD) is a classic Chinese prescription for the treatment of sleep disorder. However, the mechanism of GPD remains puzzling. In this paper, integrated pharmacological analysis and gene expression profiling were introduced to study the mechanism of GPD in treatment with SD. Firstly, the integrative pharmacology‑based research platform of traditional Chinese medicine (TCMIP) was applied to collect chemical compounds and corresponding targets for GPD. Secondly, SD‑related targets were obtained by gene expression profiling (GSE56931) from Gene Expression Omnibus (GEO) database. The String database screened the core targets according to protein‑protein interaction (PPI) network. Furthermore, kyoto encyclopedia of genes and genomes (KEGG) pathways were carried out based on the Database for Annotation, Visualization and Integrated Discovery (DAVID) database. Conclusively, the "formula‑herbs‑compounds‑targets‑pathways" network was established to explore the mechanism of GPD in the treatment of SD. In addition, molecular docking was carried out to verify the connection between hub compounds and targets. The results showed that GPD was mainly linked to 44 compounds, 19 targets and 5 pathways. GPD in the treatment of sleep deprivation through metabolic pathways and cAMP signaling pathway, which were related to NR3C1, MAPK3, PPARA and core compounds such as adenosine. This study preliminarily revealed the molecular mechanism of GPD for SD, and lays a foundation for the study of the mechanism against SD for GPD.

This study was designed to investigate a possible interaction between 17β‑estradiol and glutamate receptors of the paragigantocellularis lateralis (LPGi) nucleus on pain coping behavior using the formalin test in ovariectomized (OVX) rats. The results showed that intra‑LPGi injection of 17β‑estradiol declined flexing behavior in both phases of the formalin test. Still, it only diminished the late phase of licking behavior in the OVX rats. NMDA receptor antagonist, AP5, reversed the analgesic effect of 17β‑estradiol on flexing behavior in both phases of the formalin test in the OVX rats. The 17β‑estradiol‑induced anti‑nociceptive effect on the flexing duration was prevented by CNQX (AMPA receptor antagonist) only in the early phase of the formalin test in the OVX rats. AP5 and CNQX reduced the anti‑nociceptive effect of 17β‑estradiol in the late phase, but not the early phase of licking response in the OVX rats. These results suggested: (i) The intra‑LPGi injection of 17β‑estradiol is satisfactory in producing modest analgesia on the formalin‑induced inflammatory pain in the OVX rats; (ii) Co‑treatment of glutamate receptors (NMDA and AMPA) antagonists and 17β‑estradiol in the LPGi nucleus decrease the analgesic effect of 17β‑estradiol in the OVX rats; (iii) There is a possible association between 17β‑estradiol and glutamate receptors of the LPGi nucleus on pain coping behavior in the OVX rats.

Studies have previously demonstrated a relationship between social status and anxiety disorders such as panic disorder. Repeated episodes of panic attacks do not occur in combination with an actual fear stimulus or stressor. However, social ranking modulates the perception of the social signals of a threat or stressor. The hypothalamic nuclei are well‑known for their role in the elaboration of fear‑induced reactions. The dorsomedial hypothalamus (DMH) and the ventromedial hypothalamic (VMH) nuclei are hypothalamic subnuclei involved in the processing of threatening stimuli‑evoked aversive response and innate fear development. These structures are also located in the medial amygdala‑hypothalamus‑brainstem circuit that modulates innate fear‑induced defensive behaviors. This work aimed to investigate the relationship between social hierarchy and innate fear‑induced panic‑like responses in male rats. In our study, the dominance tube test was used to determine the social hierarchy. Then, DMH/VMH nuclei were unilaterally implanted with a guide cannula. After intra‑DMH/VMH injection of bicuculline (GABAA receptor antagonist), both innate fear induction and differences in dominant/subordinate rats were evaluated by the open field test. Intra‑DMH/VMH bicuculline increased the frequency of defensive immobility, forward escape movements, and crossing behaviors, as well as the duration of defensive immobility and forward escape movements in dominant rats. Subordinate rats showed a higher frequency of defensive attention, defensive immobility, and crossing than dominant rats. Additionally, dominant rats demonstrated a lower duration of defensive attention and defensive immobility than subordinate rats. Dominant rats seemed to adopt a form of innate‑fear characterized by increased proactivity with the environment. In contrast, subordinate rats exhibited a reactive form of innate‑fear characterized by passivity and freezing.