Immunological processes of enhancers and suppressors of long non-coding RNAs associated with brain tumors and inflammation

Immunological processes, such as inflammation, can both cause tumor suppression and cancer progression. Moreover, deregulated levels of long non-coding RNA (lncRNA) expression in the brain may cause inflammation and lead to the growth of tumors. Like other biological processes, the immune system’s role in cancer is complicated, varies, and can help or hurt the cancer’s maintenance. According to research, inflammation and brain cancer are correlated via several signaling pathways. A variety of lncRNAs have recently been revealed to influence cancer by modulating inflammatory pathways. As a result, lncRNAs have the potential to influence carcinogenesis, tumor formation, or tumor suppression via an increase or decrease in inflammation functions. Although the study and targeting of lncRNAs have made great progress in the treatment of cancer, there are definitely limitations and challenges. Using new technologies like nanocarriers and cell-penetrating peptides (CPPs) to target treatments without hurting healthy body tissues has shown to be very effective. In this review article, we have collected significantly related lncRNAs and their inhibitory or stimulating roles in inflammation and brain cancer for the first time. However, there are limitations, such as side effects and damage to normal tissues. With the advancement of new targeting technologies, these lncRNAs may be candidates for the specific targeting therapy of brain cancers by limiting inflammation or stimulating the immune system against them in the future

Chronic stress but not acute stress decreases the seizure threshold in PTZ-induced seizure in mice: role of inflammatory response and oxidative stress

Seizure is paroxysmal abnormal electrical discharges in the cerebral cortex. Inflammatory pathways and oxidative stress are involved in the pathophysiology of seizures. Stress can induce an oxidative stress state and increase the production of inflammatory mediators in the brain. We investigated the effects of acute and chronic stresses on the seizure threshold in pentylenetetrazol (PTZ)-induced seizures in mice, considering oxidative stress and inflammatory mediators in the prefrontal cortex. In this study, 30 male Naval Medical Research Institute (NMRI) mice were divided into 3 groups, including acute stress, chronic stress, and control groups. PTZ was used for the induction of seizures. The gene expression of inflammatory markers (IL-1 beta, TNF-alpha, NLRP3, and iNOS), malondialdehyde (MDA) level, nitrite level, and total antioxidant capacity (TAC) were assessed in the prefrontal cortex and serum. Our results showed that stress could increase the expression of inflammatory cytokines genes and oxidative stress in the prefrontal cortex of the brain and serum following PTZ-induced seizures, which is associated with increased seizure sensitivity and decreased the seizure threshold. The effects of chronic stress were much more significant than acute stress. We concluded that the effects of chronic stress on seizure sensitivity and enhancement of neuroinflammation and oxidative stress are much greater than acute stress

Possible role of NO/NMDA pathway in the autistic-like behaviors induced by maternal separation stress in mice

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Maternal separation (MS) stress is an established model of early-life stress associated with autistic-like behaviors. Altered glutamatergic and nitrergic neurotransmissions may contribute to the pathophysiology of ASD. However, the specific mechanisms underlying these alterations and their relationship to MS-induced autistic-like behaviors remain unclear. Addressing this knowledge gap, this study aims to elucidate the involvement of the nitric oxide (NO)/ N-methyl-D-aspartate (NMDA) pathway in MS-induced autistic-like behaviors in mice. This knowledge has the potential to guide future research, potentially leading to the development of targeted interventions or treatments aimed at modulating the NO/NMDA pathway to ameliorate ASD symptoms. Ninety male Naval Medical Research Institute (NMRI) mice were assigned to six groups (n = 15) comprising a control group (treated with saline) and five groups subjected to MS and treated with saline, ketamine, NMDA, L-NAME, and L-arginine. Behavioral tests were conducted, including the three-chamber test, shuttle box, elevated plus-maze, and marble burying test. Gene expression of iNOS, nNOS, and NMDA-R subunits (NR2A and NR2B), along with nitrite levels, was evaluated in the hippocampus. The findings demonstrated that MS induced autistic-like behaviors, accompanied by increased gene expression of iNOS, nNOS, NR2B, NR2A, and elevated nitrite levels in the hippocampus. Modulation of the NO/NMDA pathway with activators and inhibitors altered the effects of MS. These results suggest that the NO/NMDA pathway plays a role in mediating the negative effects of MS and potentially contributes to the development of autistic-like behaviors in maternally separated mice

Ellagic acid through attenuation of neuro-inflammatory response exerted antidepressant-like effects in socially isolated mice

Recent studies have been demonstrated that neuroinflammation plays a crucial role in the pathophysiology of depression. Therefore, anti-inflammatory medications could be regarded as a potentially effective treatments for depression. Ellagic acid (EA) is a natural polyphenol with antioxidant and anti-inflammatory properties. This study aimed to evaluate the antidepressant-like effect of EA in a mouse model of social isolation stress (SIS), considering its potential anti-neuroinflammatory properties. In this study, 48 male mice were divided into six groups (n = 8), including saline-treated control (socially conditioned (SC)) group and SIS (isolation conditioned (IC)) groups treated with saline or EA at doses of 12.5, 25, 50, and 100 mg/kg, respectively. Saline and EA were administrated intraperitoneally for 14 constant days. Immobility time in the forced swimming test (FST) and grooming activity time in the splash test were measured. The gene expression of inflammatory cytokines relevant to neuroinflammation was assessed in the hippocampus by real-time PCR. Results showed that SIS significantly increased immobility time in the FST and reduced grooming activity time in the splash test. In addition, the expression of inflammatory genes, including TNF-α, IL-1β, and TLR4 increased in IC mice's hippocampi. Findings showed that EA decreased immobility time in the FST and increased grooming activity time in the splash test. Moreover, EA attenuated neuroimmune-response in the hippocampus. In conclusion, finding determined that EA, through attenuation of neuroinflammation in the hippocampus, partially at least, exerted an antidepressant-like effect in the mouse model of SIS

Anticonvulsant effect of quercetin in pentylenetetrazole (PTZ)-induced seizures in male mice: The role of anti-neuroinflammatory and anti-oxidative stress

Background: Epilepsy is one of the major neurological disorders. The inflammatory process and oxidative stress are closely related to seizure progression. Quercetin is a flavonoid with anti-inflammatory and antioxidant properties as well as neuroprotective effects. We aimed to evaluate the effect of quercetin on pentylenetetrazole- (PTZ-) induced seizures in male mice focusing on its possible anti-neuroinflammatory and anti-oxidative stress. Methods: In this study, 50 male NMRI mice were divided into five groups (n = 10) and given the following treatments: normal saline, quercetin at doses of 10, 20, and 40 mg/kg, and diazepam at a dose of 10 mg/kg. In order to induce seizures, PTZ was administered intravenously. Drugs were administered intravenously 60 min before the seizure induction. The seizure threshold was measured, and finally, malondialdehyde (MDA), total antioxidant capacity (TAC), and the gene expression of IL-1β, TNF-α, NLRP3, and iNOS were determined in the prefrontal cortex. Results: It was confirmed that quercetin increased the seizure threshold. And quercetin increased TAC, and decreased levels of MDA as well as gene expression of TNF- α, NLRP3, IL-1β, and iNOS in the prefrontal cortex at the time of seizure induction. Conclusion: It was suggested that the anticonvulsant effect of quercetin in PTZ-induced seizures in mice may be due to the reduction of inflammatory responses and oxidative stress in the prefrontal cortex

The effect of MS stress and NO/NMDA mediators on the gene expression of iNOS, nNOS, NR2A, and NR2B in the hippocampus.

Values were calculated for a sample of 5 mice and reported as the mean ± S.E.M. The statistical analysis employed one-way ANOVA followed by Tukey’s post-test. *p#p##p###p<0.001 in comparison to the saline-treated MS group.</p

The primer sequences used in PCR amplification.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Maternal separation (MS) stress is an established model of early-life stress associated with autistic-like behaviors. Altered glutamatergic and nitrergic neurotransmissions may contribute to the pathophysiology of ASD. However, the specific mechanisms underlying these alterations and their relationship to MS-induced autistic-like behaviors remain unclear. Addressing this knowledge gap, this study aims to elucidate the involvement of the nitric oxide (NO)/ N-methyl-D-aspartate (NMDA) pathway in MS-induced autistic-like behaviors in mice. This knowledge has the potential to guide future research, potentially leading to the development of targeted interventions or treatments aimed at modulating the NO/NMDA pathway to ameliorate ASD symptoms. Ninety male Naval Medical Research Institute (NMRI) mice were assigned to six groups (n = 15) comprising a control group (treated with saline) and five groups subjected to MS and treated with saline, ketamine, NMDA, L-NAME, and L-arginine. Behavioral tests were conducted, including the three-chamber test, shuttle box, elevated plus-maze, and marble burying test. Gene expression of iNOS, nNOS, and NMDA-R subunits (NR2A and NR2B), along with nitrite levels, was evaluated in the hippocampus. The findings demonstrated that MS induced autistic-like behaviors, accompanied by increased gene expression of iNOS, nNOS, NR2B, NR2A, and elevated nitrite levels in the hippocampus. Modulation of the NO/NMDA pathway with activators and inhibitors altered the effects of MS. These results suggest that the NO/NMDA pathway plays a role in mediating the negative effects of MS and potentially contributes to the development of autistic-like behaviors in maternally separated mice.</div

The effect of MS stress and NO/NMDA mediators on the nitrite levels in the hippocampus.

Values were calculated for a sample of 5 mice and reported as the mean ± S.E.M. The statistical analysis employed a one-way ANOVA followed by Tukey’s post-test. ***p##p###p<0.001 in compared to the saline-treated MS group.</p

The effect of MS stress and NO/NMDA mediators on the open arms entries and time spent in open arms in the EPM.

Values were calculated for a sample of 5 mice and reported as the mean ± S.E.M. The statistical analysis employed a one-way ANOVA followed by Tukey’s post-test. *p#p##p###p<0.001 in comparison to the saline-treated MS group.</p