Sesamin mitigates lead-induced behavioral deficits in male rats: The role of oxidative stress.

Lead (Pb) is a well-known toxic pollutant that has negative effects on behavioral functions. Sesamin, a phytonutrient of the lignan class, has shown neuroprotective effects in various neurological disorder models. The present study was undertaken to evaluate the putative protective effects of sesamin against Pb-induced behavioral deficits and to identify the role of oxidative stress in male rats. The rats were exposed to 500 ppm of Pb acetate in their drinking water and simultaneously treated orally with sesamin at a dose of 30 mg/kg/day for eight consecutive weeks. Standard behavioral paradigms were used to assess the behavioral functions of the animals during the eighth week of the study. Subsequently, oxidative stress factors were evaluated in both the cerebral cortex and hippocampal regions of the rats. The results of this study showed that Pb exposure triggered anxiety-/depression-like behaviors and impaired object recognition memory, but locomotor activity was indistinguishable from the normal control rats. These behavioral deficiencies were associated with suppressed enzymatic and non-enzymatic antioxidant levels, and enhanced lipid peroxidation in the investigated brain regions. Notably, correlations were detected between behavioral deficits and oxidative stress generation in the Pb-exposed rats. Interestingly, sesamin treatment mitigated anxio-depressive-like behaviors, ameliorated object recognition memory impairment, and modulated oxidative-antioxidative status in the rats exposed to Pb. The results suggest that the anti-oxidative properties of sesamin may be one of the underlying mechanisms behind its beneficial effect in ameliorating behavioral deficits associated with Pb exposure.

LncRNA MALAT1 and Ischemic Stroke: Pathogenesis and Opportunities.

Ischemic stroke (IS) stands as a prominent cause of mortality and long-term disability around the world. It arises primarily from a disruption in cerebral blood flow, inflicting severe neural injuries. Hence, there is a pressing need to comprehensively understand the intricate mechanisms underlying IS and identify novel therapeutic targets. Recently, long noncoding RNAs (lncRNAs) have emerged as a novel class of regulatory molecules with the potential to attenuate pathogenic mechanisms following IS. Among these lncRNAs, MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) has been extensively studied due to its involvement in the pathophysiological processes of IS. In this review, we provide an in-depth analysis of the essential role of MALAT1 in the development and progression of both pathogenic and protective mechanisms following IS. These mechanisms include oxidative stress, neuroinflammation, cell death signaling, blood brain barrier dysfunction, and angiogenesis. Furthermore, we summarize the impact of MALAT1 on the susceptibility and severity of IS. This review highlights the potential risks associated with the therapeutic use of MALAT1 for IS, which are attributable to the stimulatory action of MALAT1 on ischemia/reperfusion injury. Ultimately, this review sheds light on the potential molecular mechanisms and associated signaling pathways underlying MALAT1 expression post-IS, with the aim of uncovering potential therapeutic targets.

The functions of long non-coding RNA (lncRNA)-MALAT-1 in the pathogenesis of renal cell carcinoma.

Renal cell carcinoma (RCC), a prevalent form of renal malignancy, is distinguished by its proclivity for robust tumor proliferation and metastatic dissemination. Long non-coding RNAs (lncRNAs) have emerged as pivotal modulators of gene expression, exerting substantial influence over diverse biological processes, encompassing the intricate landscape of cancer development. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1), an exemplar among lncRNAs, has been discovered to assume functional responsibilities within the context of RCC. The conspicuous expression of MALAT-1 in RCC cells has been closely linked to the advancement of tumors and an unfavorable prognosis. Experimental evidence has demonstrated the pronounced ability of MALAT-1 to stimulate RCC cell proliferation, migration, and invasion, thereby underscoring its active participation in facilitating the metastatic cascade. Furthermore, MALAT-1 has been implicated in orchestrating angiogenesis, an indispensable process for tumor expansion and metastatic dissemination, through its regulatory influence on pro-angiogenic factor expression. MALAT-1 has also been linked to the evasion of immune surveillance in RCC, as it can regulate the expression of immune checkpoint molecules and modulate the tumor microenvironment. Hence, the potential utility of MALAT-1 as a diagnostic and prognostic biomarker in RCC emerges, warranting further investigation and validation of its clinical significance. This comprehensive review provides an overview of the diverse functional roles exhibited by MALAT-1 in RCC.

Anandamide Attenuates Neurobehavioral Deficits and EEG Irregularities in the Chronic Sleep Deprivation Rats: The Role of Oxidative Stress and Neuroinflammation.

Sleep deprivation increases stress, anxiety, and depression by altering the endocannabinoid system's function. In the present study, we aimed to investigate the anti-anxiety and anti-depressant effects of the endocannabinoid anandamide (AEA) in the chronic sleep deprivation (SD) model in rats. Adult male Wistar rats (200-250 g) were randomly divided into three groups: control + vehicle (Control), chronic sleep deprivation + vehicle (SD), and chronic sleep deprivation + 20 mg/kg AEA (SD + A). The rats were kept in a sleep deprivation device for 18 h (7 to 1 a.m.) daily for 21 days. Open-field (OFT), elevated plus maze, and forced swimming tests (FST) were used to assess anxiety and depression-like behavior. As well as the cortical EEG, CB1R mRNA expression, TNF-α, IL-6, IL-4 levels, and antioxidant activity in the brain were examined following SD induction. AEA administration significantly increased the time spent (p < 0.01), the distance traveled in the central zone (p < 0.001), and the number of climbing (p < 0.05) in the OFT; it also increased the duration and number of entries into the open arms (p < 0.01 and p < 0.05 respectively), and did not reduce immobility time in the FST (p > 0.05), AEA increased CB1R mRNA expression in the anterior and medial parts of the brain (p < 0.01), and IL-4 levels (p < 0.05). AEA also reduced IL-6 and TNF-α (p < 0.05) and modulated cortical EEG. AEA induced anxiolytic-like effects but not anti-depressant effects in the SD model in rats by modulating CB1R mRNA expression, cortical EEG, and inflammatory response.

Anethole attenuates motor dysfunctions, striatal neuronal activity deficiency and blood brain barrier permeability by decreasing striatal α-synuclein and oxidative stress in rotenone-induced Parkinson's disease of male rats.

INTRODUCTION: Anethole is the main compound of the essential oil of anise and several other plants, which has antioxidant, anti-inflammatory, and neuroprotective properties. Oxidative stress is considered as an important factor in the pathogenesis of PD. In the present study, we aimed to investigate the effects of anethole against rotenone-induced PD. METHODS: Male Wistar rats were randomly divided into six groups. Control group received DMSO + sunflower oil, model group received rotenone (2 mg/kg, s.c, daily for 35 days), positive control group received L-Dopa, and test groups received anethole (62.5, 125, and 250 mg/kg, i.g, daily for 35 days) 1 hour before each rotenone injection. Body weight changes, rotarod test, stride length test, and extracellular single unit recording were performed after treatment. After behavioral test, Brain water content and blood brain barrier (BBB) permeability were evaluated, and the levels of malondialdehyde (MDA), superoxide dismutases (SOD), alpha-synuclein and MAO-B were measured in the striatum. RESULTS: Chronic administration of rotenone induced body weight loss and caused significant dysfunction in locomotor activity, neuronl firing rate, and BBB. Rotenone also decreased SOD activity, increased MDA level, and elevated the expression of alpha-synuclein and MAO-B in the striatum. However, treatment with anethole attenuated body weight loss, motor function, neuronal activity, and BBB function. Furthermore, Anethole treatment attenuated oxidative stress and decreased the expression of alpha-synuclein and MAO-B compared to the rotenone group. CONCLUSION: Our results show that through its antioxidant properties, aethole can improve the cellular, molecular and behavioral characteristics of rotenone-induced Parkinson's disease.

The Mechanisms of Long Non-coding RNA-XIST in Ischemic Stroke: Insights into Functional Roles and Therapeutic Potential.

Ischemic stroke, which occurs due to the occlusion of cerebral arteries, is a common type of stroke. Recent research has highlighted the important role of long non-coding RNAs (lncRNAs) in the development of cerebrovascular diseases, specifically ischemic stroke. Understanding the functional roles of lncRNAs in ischemic stroke is crucial, given their potential contribution to the disease pathology. One noteworthy lncRNA is X-inactive specific transcript (XIST), which exhibits downregulation during the early stages of ischemic stroke and subsequent upregulation in later stages. XIST exert its influence on the development of ischemic stroke through interactions with multiple miRNAs and transcription factors. These interactions play a significant role in the pathogenesis of the condition. In this review, we have provided a comprehensive summary of the functional roles of XIST in ischemic stroke. By investigating the involvement of XIST in the disease process, we aim to enhance our understanding of the mechanisms underlying ischemic stroke and potentially identify novel therapeutic targets.

Sesamin alleviates defects in seizure, behavioral symptoms, and hippocampus electroencephalogram in a pentylenetetrazol rat model.

Objectives: Seizure is a prevalent disorder reflected by powerful and sudden activity of neural networks in the brain that leads to tonic-clonic attacks. These signs may be due to an increase in excitatory/inhibitory neurotransmitters ratio. So, the current experiment aimed to examine the seizure and neurobehavioral parameters, as well as the hippocampus local electroencephalogram (EEG) after seizure with and without sesamin pretreatment. Materials and Methods: Sesamin (15, 30, and 60 mg/kg/5 ml, intraperitoneal or IP, vehicle: dimethyl sulfoxide or DMSO, for 3 days) was administrated before pentylenetetrazol (PTZ) (60 mg/kg/10 ml, IP, vehicle: saline), which induces acute seizure in adult male Wistar rats (230 ± 20 g, six weeks old). Different phases of seizures (score, latency, duration, and frequency), behavioral parameters (passive avoidance memory, anxiety, and locomotor activity), and hippocampus local EEG were evaluated after the injections. At the end of the experiments, oxidative stress markers plus gene expression of phosphoinositide 3-kinase/protein kinase B or PI3K/Akt mRNA were measured in the hippocampus. Results: Pretreatment with sesamin (30 mg/kg) could significantly decrease seizure scores and oxidative stress in the hippocampus. PTZ injection induced EEG deficits and neurobehavioral impairments which were significantly decreased by sesamin, especially in Beta, Theta, and delta EEG waves. Also, the expression of PI3K/Akt significantly increased in the sesamin (30 mg/kg) group in comparison with the PTZ group. Conclusion: Sesamin could prevent seizure attacks and neurobehavioral and EEG deficits induced by pentylenetetrazol, probably through the PI3K/Akt signaling pathway.

Anandamide improves food intake and orexinergic neuronal activity in the chronic sleep deprivation induction model in rats by modulating the expression of the CB1 receptor in the lateral hypothalamus.

Sleep deprivation alters orexinergic neuronal activity in the lateral hypothalamus (LH), which is the main regulator of sleep-wake, arousal, appetite, and energy regulation processes. Cannabinoid receptor (CBR) expression in this area is involved in modulating the function of orexin neurons. In this study, we investigated the effects of endocannabinoid anandamide (AEA) administration on improving food intake and appetite by modulating the activity of orexin neurons and CB1R expression after chronic sleep deprivation. Adult male Wistar rats (200-250 g) were randomly divided into three groups: control + vehicle (Control), chronic sleep deprivation + vehicle (SD), and chronic sleep deprivation +20 mg/kg AEA (SD + A). For SD induction, the rats were kept in a sleep deprivation device for 18 h (7 a.m. to 1 a.m.) daily for 21 days. Weight gain, food intake, the electrical power of orexin neurons, CB1R mRNA expression in hypothalamus, CB1R protein expression in the LH, TNF-α, IL-6, IL-4 levels and antioxidant activity in hypothalamus were measured after SD induction. Our results showed that AEA administration significantly improved food intake (p < 0.01), Electrical activity of orexin neurons (p < 0.05), CB1R expression in the hypothalamus (p < 0.05), and IL-4 levels (p < 0.05). AEA also reduced mRNA expression of OX1R and OX2R (p < 0.01 and p < 0.05 respectively), also IL-6 and TNF-α (p < 0.01) and MDA level (p < 0.05) in hypothalamic tissue. As a consequence, AEA modulates orexinergic system function and improves food intake by regulating the expression of the CB1 receptor in the LH in sleep deprived rats.

Effects of Gallic Acid on Memory Deficits and Electrophysiological Impairments Induced by Cerebral Ischemia/Reperfusion in Rats Following Exposure to Ambient Dust Storm.

We aimed to investigate the probable protective effects of gallic acid (GA) on cognitive deficits, hippocampal long term potentiation (LTP) impairments, and molecular changes induced by cerebral ischemia/reperfusion (I/R) in rats following exposure to ambient dust storm. After pretreatment with GA (100 mg/kg), or vehicle (Veh) (normal saline, 2 ml/kg) for ten days, and 60 minutes' exposure to dust storm including PM (PM, 2000-8000 g/m3) every day, 4-vessel occlusion (4VO) type of I/R was induced. Three days after I/R induction, we evaluated behavioral, electrophysiological, histopathological, molecular and brain tissue inflammatory cytokine changes. Our findings indicated that pretreatment with GA significantly reduced cognitive impairments caused by I/R (P < 0.05) and hippocampal LTP impairments caused by I/R after PM exposure (P < 0.001). Additionally, after exposure to PM, I/R significantly elevated the tumor necrosis factor α content (P < 0.01) and miR-124 level (P < 0.001) while pre-treatment with GA reduced the level of miR-124 (P < 0.001). Histopathological results also revealed that I/R and PM caused cell death in the hippocampus CA1 area (P < 0.001) and that GA decreased the rate of cell death (P < 0.001). Our findings show that GA can prevent brain inflammation, and thus cognitive and LTP deficits caused by I/R, PM exposure, or both.

Anti-inflammatory, anti-apoptotic, and neuroprotective potentials of anethole in Parkinson's disease-like motor and non-motor symptoms induced by rotenone in rats.

Parkinson's disease (PD) is a complex neurological disorder characterized by a combination of motor and non-motor symptoms (NMS). Antioxidant and anti-inflammatory compounds are considered a potential therapeutic strategy against PD. The present study examined the neuroprotective effects of anethole as a potent antioxidant and anti-inflammatory agent against motor and non-motor deficits induced by rotenone toxicity. Rats were treated with anethole (62.5, 125, and 250 mg/kg, i.g) concomitantly with rotenone (2 mg/kg, s.c) for 5 weeks. After the treatment, behavioral tests were performed to evaluate motor function and depression-/anxiety-like behaviors. After the behavioral tests, rats were decapitated and brains were removed for histological analysis. Striatum samples were also isolated for neurochemical, and molecular analysis. Our data showed that rotenone-induced motor deficit, anxiety-and depression-like behaviors were significantly improved in rats treated with anethole. Furthermore, anethole treatment reduced inflammatory cytokines tumor necrosis factor α (TNFα) and Interleukin 6 (IL-6), and increased anti-inflammatory cytokine IL-4 in the striatum of rotenone-induced PD rats. Western blot analysis showed that treatment with anethole markedly suppressed caspase-3 activation induced by rotenone. Moreover, histological examination of striatum showed an increase in the number of surviving neurons after treatment with anethole. Anethole also significantly enhanced the striatal levels of dopamine in rotenone-induced PD rats. In addition, treatment with L-Dopa as a positive control group had effects similar to those of anethole on histological, neurochemical, and molecular parameters in rotenone-induced parkinsonian rats. Our results suggested the neuroprotective effects of anethole through anti-inflammatory, anti-apoptotic, and antioxidant mechanisms against rotenone-induced toxicity in rats.

Exogenous growth hormone administration during total sleep deprivation changed the microRNA-9 and dopamine D2 receptor expressions followed by improvement in the hippocampal synaptic potential, spatial cognition, and inflammation in rats.

RATIONALE: Disorders caused by total sleep deprivation can be modulated by the administration of growth hormone, which could affect the expression of microRNA-9 and dopamine D2 receptor expressions followed by improvement in the hippocampal synaptic potential, spatial cognition, and inflammation in rats. OBJECTIVES: The present study aimed to elucidate the putative effects of exogenous growth hormone (GH) against total sleep deprivation (TSD)-induced learning and memory dysfunctions and possible involved mechanisms. METHODS: To induce TSD, rats were housed in homemade special cages equipped with stainless steel wire conductors to induce general and inconsistent TSD. They received a mild repetitive electric shock to their paws every 10 min for 21 days. GH (1 mg/kg, sc) was administered to adult young male rats once daily for 21-day-duration induction of TSD. Spatial learning and memory performance, inflammatory status, microRNA-9 (miR-9) expression, dopamine D2 receptor (DRD2) protein level, and hippocampal histological changes were assayed at scheduled times after TSD. RESULTS: The results indicated that TSD impaired spatial cognition, increased TNF-α, decreased level of miR-9, and increased DRD2 levels. Treatment with exogenous GH improved spatial cognition, decreased TNF-α, increased level of miR-9, and decreased DRD2 levels after TSD. CONCLUSIONS: Our findings suggest that GH may play a key role in the modulation of learning and memory disorders as well as the ameliorating abnormal DRD2-related functional disorders associated with miR-9 in TSD.

An updated review of contribution of long noncoding RNA-NEAT1 to the progression of human cancers.

Long non-coding RNAs (lncRNAs) present pivotal roles in cancer tumorigenesis and progression. Recently, nuclear paraspeckle assembly transcript 1 (NEAT1) as a lncRNA has been shown to mediate cell proliferation, migration, and EMT in tumor cells. NEAT1 by targeting several miRNAs/mRNA axes could regulate cancer cell behavior. Therefore, NEAT1 may function as a potent biomarker for the prediction and treatment of some human cancers. In this review, we summarized various NEAT1-related signaling pathways that are critical in cancer initiation and progression.

Administration of growth hormone ameliorates adverse effects of total sleep deprivation.

Total sleep deprivation (TSD) causes several harmful changes including anxiety, inflammation, and increased expression of extracellular signal-regulated kinase (ERK) and tropomyosin receptor kinase B (TrkB) genes in the hippocampus. The current study was conducted to explain the possible effects of exogenous GH against the above parameters caused by TSD and the possible mechanisms involved. Male Wistar rats were divided into 1) control, 2) TSD and 3) TSD + GH groups. To induce TSD, the rats received a mild repetitive electric shock (2 mA, 3 s) to their paws every 10 min for 21 days. Rats in the third group received GH (1 ml/kg, sc) for 21 days as treatment for TSD. The motor coordination, locomotion, the level of IL-6, and expression of ERK and TrkB genes in hippocampal tissue were measured after TSD. The motor coordination (p < 0.001) and locomotion indices (p < 0.001) were impaired significantly by TSD. The concentrations of serum corticotropin-releasing hormone (CRH) (p < 0.001) and hippocampal interleukin-6 (IL-6) (p < 0.001) increased. However, there was a significant decrease in the interleukin-4 (IL-4) concentration and expression of ERK (p < 0.001) and TrkB (p < 0.001) genes in the hippocampus of rats with TSD. Treatment of TSD rats with GH improved motor balance (p < 0.001) and locomotion (p < 0.001), decreased serum CRH (p < 0.001), IL-6 (p < 0.01) but increased the IL-4 and expression of ERK (p < 0.001) and TrkB (p < 0.001) genes in the hippocampus. Results show that GH plays a key role in modulating the stress hormone, inflammation, and the expression of ERK and TrkB genes in the hippocampus following stress during TSD.

Mitochondrial Dysfunction and Parkinson's Disease: Pathogenesis and Therapeutic Strategies.

Parkinson's disease (PD) is a common age-related neurodegenerative disorder whose pathogenesis is not completely understood. Mitochondrial dysfunction and increased oxidative stress have been considered as major causes and central events responsible for the progressive degeneration of dopaminergic (DA) neurons in PD. Therefore, investigating mitochondrial disorders plays a role in understanding the pathogenesis of PD and can be an important therapeutic target for this disease. This study discusses the effect of environmental, genetic and biological factors on mitochondrial dysfunction and also focuses on the mitochondrial molecular mechanisms underlying neurodegeneration, and its possible therapeutic targets in PD, including reactive oxygen species generation, calcium overload, inflammasome activation, apoptosis, mitophagy, mitochondrial biogenesis, and mitochondrial dynamics. Other potential therapeutic strategies such as mitochondrial transfer/transplantation, targeting microRNAs, using stem cells, photobiomodulation, diet, and exercise were also discussed in this review, which may provide valuable insights into clinical aspects. A better understanding of the roles of mitochondria in the pathophysiology of PD may provide a rationale for designing novel therapeutic interventions in our fight against PD.