Neurotox Res [JOURNAL]
Sun
200 papers
Catalpol Mitigates Alzheimer's Disease Progression by Promoting the Expression of Neural Stem Cell Exosomes Released miR-138-5p.
Meng S, Chen H, Deng C … +1 more , Meng Z
Neurotox Res · 2023 Feb · PMID 36595161 · Full text
Alzheimer's disease (Alzheimer's disease, AD) is a neurodegenerative disease characterized by senile plaque deposition and neurofibrillary tangles. The pathogenesis of AD is complicated and the drugs used to treat AD are...
Alzheimer's disease (Alzheimer's disease, AD) is a neurodegenerative disease characterized by senile plaque deposition and neurofibrillary tangles. The pathogenesis of AD is complicated and the drugs used to treat AD are single-targeted drugs, which can only improve or alleviate the symptoms of patients, but cannot delay or prevent the progress of the disease. Because of its ability to act on multiple targets, multiple systems, multiple links, and multiple pathways, Chinese herbal compound prescriptions have shown unique advantages in the research and treatment of AD. Our previous study has demonstrated the protect role of the Chinese medicine Rehmannia in AD. However, the underlying mechanism remains unclear. In the present study, both in vitro and vivo experiments were employed, and we found Catalpol (Ca), the main extract of Rehmannia, could mitigate AD progression both in vitro and in vivo by promoting miR-138-5p level in neural stem cell secreted exosomes.
Dihydromyricetin Protects Against Salsolinol-Induced Toxicity in Dopaminergic Cell Line: Implication for Parkinson's Disease.
Getachew B, Csoka AB, Copeland RL … +2 more , Manaye KF, Tizabi Y
Neurotox Res · 2023 Apr · PMID 36585544 · Publisher ↗
Parkinson's disease (PD) is a progressive neurodegenerative disease associated with loss of dopaminergic neurons in the substantia nigra pars compacta. Although aging is the primary cause, environmental and genetic facto...
Parkinson's disease (PD) is a progressive neurodegenerative disease associated with loss of dopaminergic neurons in the substantia nigra pars compacta. Although aging is the primary cause, environmental and genetic factors have also been implicated in its etiology. In fact, the sporadic nature of PD (i.e., unknown etiology) renders the uncovering of the exact pathogenic mechanism(s) or development of effective pharmacotherapies challenging. In search of novel neuroprotectants, we showed that butyrate (BUT), a short-chain fatty acid, protects against salsolinol (SALS)-induced toxicity in human neuroblastoma-derived SH-SY5Y cells, which are considered an in-vitro model of PD. Dihydromyricetin (DHM), a flavonoid derived from Asian medicinal plant, has also shown effectiveness against oxidative damage and neuroinflammation, hallmarks of neurodegenerative diseases. Here we show that pretreatment of SH-SY5Y cells with DHM concentration-dependently prevented SALS-induced toxicity and that a combination of DHM and BUT resulted in a synergistic protection. The effects of both DHM and BUT in turn could be completely blocked by flumazenil (FLU), a GABA antagonist acting at benzodiazepine receptor site, and by bicuculline (BIC), a GABA antagonist acting at orthosteric site. Beta-hydroxybutyrate (BHB), a free fatty acid 3 (FA3) receptor antagonist, also fully blocked the protective effect of DHM. BHB was shown previously to only partially block the protective effect of BUT. Thus, there are some overlaps and some distinct differences in protective mechanisms of DHM and BUT against SALS-induced toxicity. It is suggested that a combination of DHM and BUT may have therapeutic potential in PD. However, further in-vivo verifications are necessary.
CircUBE3B High Expression Participates in Sevoflurane-Induced Human Hippocampal Neuron Injury via Targeting miR-326 and Regulating MYD88 Expression.
Qian X, Zheng S, Yu Y
Neurotox Res · 2023 Feb · PMID 36585543 · Publisher ↗
The clinical application of Sevoflurane (Sevo) brings about non-negligible neuron injury, leading to postoperative cognitive dysfunction (POCD). However, related pathogenesis is complex and not fully established. We aime...
The clinical application of Sevoflurane (Sevo) brings about non-negligible neuron injury, leading to postoperative cognitive dysfunction (POCD). However, related pathogenesis is complex and not fully established. We aimed to disclose the role of circRNA UBE3B (circUBE3B) in neuron injury induced by Sevo. Cell viability and apoptosis were determined by CCK-8 and flow cytometry experiments. Inflammation production was monitored by ELISA. The expression of circUBE3B, miR-326, and myeloid differentiation factor 88 (MYD88) mRNA was assessed by quantitative real-time PCR (qPCR). Apoptosis-associated markers and MYD88 protein were quantified by western blot. The putative binding site between miR-326 and circUBE3B or MYD88 was verified by a dual-luciferase reporter experiment, and their binding was validated by a pull-down assay. Sevo treatment weakened cell viability and promoted cell apoptosis and inflammatory response. CircUBE3B expression was elevated in Sevo-treated neurons. Sevo-induced neuron injury was alleviated by circUBE3B downregulation but aggravated by circUBE3B overexpression. MiR-326 was targeted by circUBE3B, and miR-326 inhibition recovered neuron injury that was repressed by circUBE3B absence in Sevo-treated neurons. MiR-326 interacted with MYD88. MiR-326 enrichment attenuated Sevo-induced neuron injury, while these effects were reversed by MYD88 overexpression. CircUBE3B dysregulation was involved in Sevo-induced human hippocampal neuron injury via targeting the miR-326/MYD88 network.
L-2-Hydroxyglutaric Acid Administration to Neonatal Rats Elicits Marked Neurochemical Alterations and Long-Term Neurobehavioral Disabilities Mediated by Oxidative Stress.
Ribeiro RT, Carvalho AVS, Palavro R … +5 more , Durán-Carabali LE, Zemniaçak ÂB, Amaral AU, Netto CA, Wajner M
Neurotox Res · 2023 Apr · PMID 36580261 · Publisher ↗
L-2-Hydroxyglutaric aciduria (L-2-HGA) is an inherited neurometabolic disorder caused by deficient activity of L-2-hydroxyglutarate dehydrogenase. L-2-Hydroxyglutaric acid (L-2-HG) accumulation in the brain and biologica...
L-2-Hydroxyglutaric aciduria (L-2-HGA) is an inherited neurometabolic disorder caused by deficient activity of L-2-hydroxyglutarate dehydrogenase. L-2-Hydroxyglutaric acid (L-2-HG) accumulation in the brain and biological fluids is the biochemical hallmark of this disease. Patients present exclusively neurological symptoms and brain abnormalities, particularly in the cerebral cortex, basal ganglia, and cerebellum. Since the pathogenesis of this disorder is still poorly established, we investigated the short-lived effects of an intracerebroventricular injection of L-2-HG to neonatal rats on redox homeostasis in the cerebellum, which is mostly affected in this disorder. We also determined immunohistochemical landmarks of neuronal viability (NeuN), astrogliosis (S100B and GFAP), microglia activation (Iba1), and myelination (MBP and CNPase) in the cerebral cortex and striatum following L-2-HG administration. Finally, the neuromotor development and cognitive abilities were examined. L-2-HG elicited oxidative stress in the cerebellum 6 h after its injection, which was verified by increased reactive oxygen species production, lipid oxidative damage, and altered antioxidant defenses (decreased concentrations of reduced glutathione and increased glutathione peroxidase and superoxide dismutase activities). L-2-HG also decreased the content of NeuN, MBP, and CNPase, and increased S100B, GFAP, and Iba1 in the cerebral cortex and striatum at postnatal days 15 and 75, implying long-standing neuronal loss, demyelination, astrocyte reactivity, and increased inflammatory response, respectively. Finally, L-2-HG administration caused a delay in neuromotor development and a deficit of cognition in adult animals. Importantly, the antioxidant melatonin prevented L-2-HG-induced deleterious neurochemical, immunohistochemical, and behavioral effects, indicating that oxidative stress may be central to the pathogenesis of brain damage in L-2-HGA.
Protective Mechanisms of 3-Acetyl-11-keto-β-Boswellic Acid and Piperine in Fluid Percussion Rat Model of Traumatic Brain Injury Targeting Nrf2 and NFkB Signaling.
Kundu S, Singh S
Neurotox Res · 2023 Feb · PMID 36576717 · Publisher ↗
The current study aimed to investigate the neuroprotective effect of 3-acetyl-11-keto-β-boswellic acid (AKBA) in combination with bioenhancer piperine in lateral fluid percussion injury-induced TBI in experimental rats....
The current study aimed to investigate the neuroprotective effect of 3-acetyl-11-keto-β-boswellic acid (AKBA) in combination with bioenhancer piperine in lateral fluid percussion injury-induced TBI in experimental rats. Fluid percussion injury was introduced in the rat brain by delivering 50 mmHg of pressure for 3 min to the exposed brain. AKBA 25 mg/kg, 50 mg/kg orally, and AKBA (25 mg/kg, p.o.) in combination with piperine (2.5 mg/kg, p.o.) were administered from day 1 to day 14 to the assigned groups. On the 1st, 7th, and 14th day, behavioral parameters were checked. On the 15th day, animals were euthanized. In TBI rat model, AKBA-piperine combination significantly restored the altered performance of grip strength, rotarod test, open field task, narrow beam task (beam crossing time and no. of foot slips), and Morris water maze (escape latency and time spent in target quadrant) (p < 0.001 vs TBI control). Furthermore, the AKBA-piperine combination significantly reduced pro-inflammatory cytokine level in TBI rat model (p < 0.001 vs TBI control). The combined effect of AKBA and piperine significantly restored oxidative stress parameters level, catecholamines level, and neurotransmitters level (p < 0.001 vs TBI control). Further findings showed that the AKBA-piperine combination prevented histopathological changes (p < 0.001), and the immunohistological study confirmed increased Nrf2-positive cells (p < 0.001 vs TBI control) and reduced nuclear factor kappa B (NFkB) expression (p < 0.001 vs TBI control, p < 0.01 vs TBI + AKBA 50 mg/kg) in the cortical region following AKBA-piperine administration. The present study concluded that AKBA along with piperine achieved anti-oxidant, and anti-inflammatory effects, and also prevented neuronal injury via targeting Nrf2 and NFkB expressions.
Therapeutic Molecular Insights into the Active Engagement of Cannabinoids in the Therapy of Parkinson's Disease: A Novel and Futuristic Approach.
Jain V, Behl T, Sehgal A … +6 more , Singh S, Sharma N, Makeen HA, Albratty M, Meraya AM, Najmi A
Neurotox Res · 2023 Feb · PMID 36567416 · Publisher ↗
Parkinson's disease is a neurodegenerative disorder which is characterised mostly by loss of dopaminergic nerve cells throughout the nigral area mainly as a consequence of oxidative stress. Muscle stiffness, disorganised...
Parkinson's disease is a neurodegenerative disorder which is characterised mostly by loss of dopaminergic nerve cells throughout the nigral area mainly as a consequence of oxidative stress. Muscle stiffness, disorganised bodily responses, disturbed sleep, weariness, amnesia, and voice impairment are all symptoms of dopaminergic neuron degeneration and existing symptomatic treatments are important to arrest additional neuronal death. Some cannabinoids have recently been demonstrated as robust antioxidants that might protect the nerve cells from degeneration even when cannabinoid receptors are not triggered. Cannabinoids are likely to have property to slow or presumably cease the steady deterioration of the brain's dopaminergic systems, a condition for which there is now no treatment. The use of cannabinoids in combination with currently available drugs has the potential to introduce a radically new paradigm for treatment of Parkinson's disease, making it immensely useful in the treatment of such a debilitating illness.
Understanding the Intricate Role of Exosomes in Pathogenesis of Alzheimer's Disease.
Chauhan S, Behl T, Sehgal A … +7 more , Singh S, Sharma N, Gupta S, Albratty M, Najmi A, Meraya AM, Alhazmi HA
Neurotox Res · 2022 Dec · PMID 36564606 · Publisher ↗
Alzheimer's disease causes loss of memory and deterioration of mental abilities is utmost predominant neurodegenerative disease accounting 70-80% cases of dementia. The appearance of plaques of amyloid-β and neurofibrill...
Alzheimer's disease causes loss of memory and deterioration of mental abilities is utmost predominant neurodegenerative disease accounting 70-80% cases of dementia. The appearance of plaques of amyloid-β and neurofibrillary tangles in the brain post-mortems of Alzheimer's patients established them as key participants in the etiology of Alzheimer's disease. Exosomes exist as extracellular vesicles of nano-size which are present throughout the body. Exosomes are known to spread toxic hyperphosphorylated tau and amyloid-β between the cells and are linked to the loss of neurons by inducing apoptosis. Exosomes have progressed from cell trashcans to multifunctional organelles which are involved in various functions like internalisation and transmission of macromolecules such as lipids, proteins, and nucleic acids. This review covers current findings on relationship of exosomes in biogenesis and angiogenesis of Alzheimer's disease and functions of exosomes in the etiology of AD. Furthermore, the roles of exosomes in development, diagnosis, treatment, and its importance as therapeutic targets and biomarkers for Alzheimer's disease have also been highlighted.
Involvement of LARP7 in Activation of SIRT1 to Inhibit NF-κB Signaling Protects Microglia from Acrylamide-Induced Neuroinflammation.
Guo J, Xue H, Zhong H … +4 more , Sun W, Zhao S, Meng J, Jiang P
Neurotox Res · 2022 Dec · PMID 36550222 · Publisher ↗
Acrylamide (AM) is a potent neurotoxin and carcinogen that is mainly formed by the Maillard reaction of asparagine with starch at high temperatures. However, the toxicity mechanism underlying AM has not been investigated...
Acrylamide (AM) is a potent neurotoxin and carcinogen that is mainly formed by the Maillard reaction of asparagine with starch at high temperatures. However, the toxicity mechanism underlying AM has not been investigated from a proteomic perspective, and the regulation of protein expression by AM remains poorly understood. This research was the first to utilize proteomics to explore the mechanism of AM exposure-induced neuroinflammation. Target proteins were obtained by differential protein analysis, functional annotation, and enrichment analysis of proteomics. Then, molecular biology methods, including Western blot, qPCR, and immunofluorescence, were used to verify the results and explore possible mechanisms. We identified 100 key differential metabolites by proteomic analysis, which was involved in the occurrence of various biological functions. Among them, the KEGG pathway enrichment analysis showed that the differential proteins were enriched in the P53 pathway, sulfur metabolism pathway, and ferroptosis. Finally, the differential target protein we locked was LARP7. Molecular biological verification found that AM exposure inhibited the expression of LARP7 and induced the burst of inflammation, while SRT1720 agonist treatment showed no effect on LARP7, but significant changes in inflammatory factors and NF-κB. Taken together, these findings suggested that AM may activate NF-κB to induce neuroinflammation by inhibiting the LARP7-SIRT1 pathway. And our study provided a direction for AM-induced neurotoxicity through proteomics and multiple biological analysis methods.
Valproic Acid Attenuated PTZ-induced Oxidative Stress, Inflammation, and Apoptosis in the SH-SY5Y Cells via Modulating the TRPM2 Channel.
Ahlatcı A, Yıldızhan K, Tülüce Y … +1 more , Bektaş M
Neurotox Res · 2022 Dec · PMID 36536269 · Publisher ↗
Valproic acid (VPA) is one of the most widely used antiepileptic drugs. The protective role of VPA and the role of the TRPM2 channel in this mechanism in developing neuronal damage due to increased pentylenetetrazol (PTZ...
Valproic acid (VPA) is one of the most widely used antiepileptic drugs. The protective role of VPA and the role of the TRPM2 channel in this mechanism in developing neuronal damage due to increased pentylenetetrazol (PTZ)-induced neurotoxicity in SH-SY5Y cells were not clarified. Here, we investigated the role of VPA via modulation of TRPM2 channel on cell death and oxidative neurotoxicity in SH-SY5Y cells. The SH-SY5Y cell toxicity model was constructed by treating SH-SY5Y cells with PTZ. The VPA and TRPM2 channel antagonist N-(p-amylcinnamoyl) anthranilic acid (ACA) were added to prevent neurotoxicity in PTZ-induced SH-SY5Y cells. The role of the VPA and TRPM2 channel was evaluated using an ELISA kit and patch-clamp. Primarily, antioxidant (GSH and GSH-Px) and oxidative stress (MDA and ROS) levels and inflammatory factors (IL-1β, IL-6, and TNF-α) in cells were determined by ELISA kits. Then, TRPM2 channel activation in cells was detected using both the ELISA kit and patch-clamp methods. In addition, apoptosis and cell viability levels in cells were determined by performing PARP1, caspase-3, caspase-9, and CCK-8 assays by ELISA kits. Our results showed that the TRPM2 channel is vital in damage formation in PTZ-induced cells. Furthermore, we observed that VPA attenuated PTZ-induced neurotoxicity by suppressing cells' oxidative stress and inflammation, and reducing TRPM2 channel activation. In our study, in which the protective effect of VPA and the role of the TRPM2 channel in PTZ-induced SH-SY5Y cells were investigated for the first time, we can conclude that VPA treatment and TRPM2 channel blockade can suppress PTZ-induced neurotoxicity.
Modulatory Activity of the Endocannabinoid System in the Development and Proliferation of Cells in the CNS.
Ruiz-Contreras HA, Santamaría A, Arellano-Mendoza MG … +3 more , Sánchez-Chapul L, Robles-Bañuelos B, Rangel-López E
Neurotox Res · 2022 Dec · PMID 36522511 · Publisher ↗
The Endocannabinoid System (ECS, also known as Endocannabinoidome) plays a key role in the function of the Central Nervous System, though the participation of this system on the early development - specifically in neurop...
The Endocannabinoid System (ECS, also known as Endocannabinoidome) plays a key role in the function of the Central Nervous System, though the participation of this system on the early development - specifically in neuroprotection and proliferation of nerve cells - has been poorly studied. Here, we collect and describe evidence regarding how cannabinoid receptors CB1R and CB2R regulate several cell markers related to proliferation. While CB1R participates in the modulation of neuronal and glial proliferation, CB2R is involved in the proliferation of glial cells. The endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) exert significant effects on nerve cell proliferation. AEA generated during embryogenesis induces major effects on the differentiation of neuronal progenitor cells, whereas 2-AG participates in modulating cell migration events rather than affecting the neural proliferation rate. However, although the ECS has been demonstrated to participate in neuroprotection, more characterization on its role in neuronal and glial proliferation and differentiation is needed, especially in brain areas with recognized high neurogenesis rates. This has encouraged scientists to elucidate and propose specific mechanisms related with these cell proliferation mechanisms to better understand some neurodegenerative disorders such as Parkinson, Huntington and Alzheimer diseases, in which neuronal loss and poor neurogenesis are crucial factors for their onset and progression. In this review, we collect and present recent evidence published pointing to an active role of the ECS in the development and proliferation of nerve cells.
Antidepressant-Like Effects of Edaravone and Minocycline: Investigation of Oxidative Stress, Neuroinflammation, Neurotrophic, and Apoptotic Pathways.
Motafeghi F, Bagheri A, Seyedabadi M … +2 more , Shaki F, Shokrzadeh M
Neurotox Res · 2022 Dec · PMID 36522510 · Publisher ↗
Depression is a very common mental disorder and mechanism that is associated with mitochondrial dysfunction. In the present study, we examined the mechanisms of action of isolated brain mitochondria in rats with depressi...
Depression is a very common mental disorder and mechanism that is associated with mitochondrial dysfunction. In the present study, we examined the mechanisms of action of isolated brain mitochondria in rats with depression for the first time. This will help identify the mitochondrial protective pathways of the two drugs and shed light on new therapeutic goals for developing antidepressants. Forced swimming, tail suspension, and sucrose preference tests were used to assess depressive-like behaviors and the oxidative stress factors of brain tissue, and measure the gene expression of apoptotic and anti-apoptotic, neuroplasticity, and neuroinflammatory factors by RT-PCR and acetylcholinesterase (AChE) activity in brain tissue (hippocampus and prefrontal) and the serum levels of corticosterone and fasting blood sugar. The results showed that the separation of neonatal rats from their mothers induced depressive-like behaviors, weight loss, mitochondrial dysfunction, increased expression of genes involved in neuroinflammation, apoptosis, genes involved in the depressive process, and decreased expression of genes involved in mood in both the hippocampus and prefrontal cortex. Maternal separation increased serum corticosterone levels, caused dysfunction of the cholinergic system, and also increased AChE activity. Treatment with different concentrations of minocycline and edaravone (1, 20, and 50 mg/kg), 5MTHF, and citalopram for 14 days showed that these drugs improved depression-like behaviors and mitochondrial function. It also reduced the expression of genes involved in neuroinflammation, apoptosis, and depression and increased the expression of genes involved in mood. In conclusion, minocycline and edaravone have neuroprotective, mitochondrial protective, antioxidant, anti-inflammatory, and anti-apoptotic effects against depressive-like behaviors caused by chronic stress.
Neurotoxicity of Bisphenol A and the Impact of Melatonin Administration on Oxidative Stress, ERK/NF-kB Signaling Pathway, and Behavior in Rats.
Sevastre-Berghian AC, Casandra C, Gheban D … +5 more , Olteanu D, Olanescu Vaida Voevod MC, Rogojan L, Filip GA, Bâldea I
Neurotox Res · 2022 Dec · PMID 36515867 · Publisher ↗
Bisphenol A (BPA) exposure can be associated with neurodevelopmental disorders due to impairment of cell proliferation and synaptic development. Our study evaluated the effects of melatonin (MEL) on ambulatory activity,...
Bisphenol A (BPA) exposure can be associated with neurodevelopmental disorders due to impairment of cell proliferation and synaptic development. Our study evaluated the effects of melatonin (MEL) on ambulatory activity, lipid peroxidation, cytokines, ERK/NF-kB signaling pathway in the hippocampus and frontal lobe, and histopathological changes in the hippocampus of the BPA-treated rats. The animals were divided into 4 groups: control, BPA, BPA + MEL I, and BPA + MEL II. MEL I (20 mg/kg b.w.) and MEL II (40 mg/kg b.w.) were orally administered for 28 days. On the 29th day, BPA (1 mg/kg b.w.) was intraperitoneally administered, and, after 24 h, an open field test (OFT) and an elevated plus maze (EPM) were conducted. The results showed that the MEL II group made significantly more entries in the open arms of EPM, traveled significantly greater distance, and spent more time in the central part of OFT. Malondialdehyde levels were diminished by MEL II in the hippocampus and by MEL I in the frontal lobe. In the hippocampus, the MAPK level was significantly lowered by both doses of MEL (p < 0.05) while in the frontal lobe, only MEL II reduced the MAPK activation. MEL I and II significantly decreased the γH2AX and upregulated the NFkB and pNFkB expressions in the hippocampus while MEL II downregulated the MCP1 expression. Both doses of MEL attenuated the BPA-evoked histopathological alterations in the hippocampus. These data indicate that MEL can mediate the neuroprotection against BPA-induced neurotoxicity and improves behavioral changes suggesting a real potential as a protective agent in brain toxicity.
miR-200a-3p Regulates PRKACB and Participates in Aluminium-Induced Tau Phosphorylation in PC12 Cells.
Li H, Liu Q, Zhang Q … +5 more , Xue X, Zhang J, Zhang J, Lin L, Niu Q
Neurotox Res · 2022 Dec · PMID 36459375 · Full text
Aluminium (Al) is an environmental neurotoxin that humans are widely exposed to, but the molecular mechanism of its toxic effects is not fully understood. Many studies have shown that exposure to Al can cause abnormal ph...
Aluminium (Al) is an environmental neurotoxin that humans are widely exposed to, but the molecular mechanism of its toxic effects is not fully understood. Many studies have shown that exposure to Al can cause abnormal phosphorylation of the tau protein that is believed as one of pathological features of Alzheimer's disease. Increasing evidence indicates that microRNAs (miRNAs) may be involved in the pathological processes of neurodegenerative diseases and are potential regulatory factors for related target genes. Phosphorylation at Ser-133 of cAMP response element-binding protein (CREB) is one of the major pathways of CREB activation, and phosphorylation at this site is controlled by protein kinase A (PKA). The catalytic subunit of PKA, cAMP-dependent protein kinase catalytic subunit beta (PRKACB), phosphorylates CREB. The target gene prediction software TargetScan showed that PRKACB was one of the target mRNAs of miR-200a-3p. The purpose of this study was to investigate whether miR-200a-3p regulates the PKA/CREB pathway by targeting PRKACB and leads to abnormal phosphorylation of the tau protein in nerve cells. The results showed that Al exposure increased the expression level of miR-200a-3p, and miR-200a-3p increased the expression of targeted downregulated PRKACB, and then decreased the PKA/CREB signalling pathway activity, leading to abnormal hyperphosphorylation of tau.
Salsolinol Induces Parkinson's Disease Through Activating NLRP3-Dependent Pyroptosis and the Neuroprotective Effect of Acteoside.
Wang Y, Wu S, Li Q … +6 more , Lang W, Li W, Jiang X, Wan Z, Sun H, Wang H
Neurotox Res · 2022 Dec · PMID 36454451 · Publisher ↗
Endogenous neurotoxin 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroiso-quinoline (Salsolinol, SAL) is a dopamine metabolite that is toxic to dopaminergic neurons in vitro and in vivo, and is involved in the pathogenesis of P...
Endogenous neurotoxin 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroiso-quinoline (Salsolinol, SAL) is a dopamine metabolite that is toxic to dopaminergic neurons in vitro and in vivo, and is involved in the pathogenesis of Parkinson's disease (PD). However, the molecular mechanism by which SAL induces neurotoxicity in PD remains challenging for future investigations. This study found that SAL induced neurotoxicity in SH-SY5Y cells and mice. RNA sequencing (RNAseq) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to detect differentially expressed genes in SAL-treated SH-SY5Y cells. We found that NLR family pyrin domain-containing 3 (NLRP3)-dependent pyroptosis was enriched by SAL, which was validated by in vitro and in vivo SAL models. Further, NLRP3 inflammasome-related genes (ASC, NLRP3, active caspase 1, IL-1β, and IL-18) were increased at the mRNA and protein level. Acteoside mitigates SAL-induced neurotoxicity by inhibiting NLRP3 inflammasome-related pyroptosis in in vitro and in vivo PD models. In summary, the present study suggests for the first time that NLRP3-dependent pyroptosis plays a role in the pathogenesis of SAL-induced PD, and acteoside mitigates SAL-induced pyroptosis-dependent neurotoxicity in in vitro and in vivo PD models. The present results demonstrated a new mechanism whereby SAL mediates neurotoxicity by activating NLRP3-dependent pyroptosis, further highlighting SAL-induced pyroptosis-dependent neurotoxicity as a potential therapeutic target in PD.
Antitumor Effect of Traditional Drugs for Neurological Disorders: Preliminary Studies in Neural Tumor Cell Lines.
Doello K, Mesas C, Quiñonero F … +4 more , Rama AR, Vélez C, Perazzoli G, Ortiz R
Neurotox Res · 2022 Dec · PMID 36447028 · Full text
Glioblastoma multiforme is the most common malignant primary brain tumor in adults. Despite new treatments developed including immunomodulation using vaccines and cell therapies, mortality remains high due to the resista...
Glioblastoma multiforme is the most common malignant primary brain tumor in adults. Despite new treatments developed including immunomodulation using vaccines and cell therapies, mortality remains high due to the resistance mechanisms presented by these tumor cells and the function of the blood-brain barrier that prevents the entry of most drugs. In this context of searching for new glioblastoma therapies, the study of the existing drugs to treat neurological disorder is gaining great relevance. The aim of this study was to determine, through a preliminary in vitro study on human glioblastoma (A172, LN229), anaplastic glioma (SF268) and neuroblastoma (SK-N-SH) cell lines, the possible antitumor activity of the active principles of several drugs (levomepromazine, haloperidol, lacosamide, valproic acid, levetiracetam, glatiramer acetate, fingolimod, biperiden and dextromethorphan) with the ability to cross the blood-brain barrier and that are commonly used in neurological disorders. Results showed that levetiracetam, valproic acid, and haloperidol were able to induce a relevant synergistic antitumor effect when associated with the chemotherapy currently used in clinic (temozolomide). Regarding the mechanism of action, haloperidol, valproic acid and levomepromazine caused cell death by apoptosis, while biperiden and dextromethorphan induced autophagy. Fingolimod appeared to have anoikis-related cell death. Thus, the assayed drugs which are able to cross the blood-brain barrier could represent a possibility to improve the treatment of neural tumors, though future in vivo studies and clinical trials will be necessary to validate it.
Medicarpin Improves Depressive-Like Behaviors in a Chronic Unpredictable Mild Stress-Induced Mouse Model of Depression by Upregulating Liver X Receptor β Expression in the Amygdala.
Li Y, He X, Zhang J … +3 more , Zhou Q, Liu X, Zhou G
Neurotox Res · 2022 Dec · PMID 36445678 · Publisher ↗
Presently, the regulatory mechanism underlying depression is indistinct, and almost 50% of depression sufferers undergo no apparent effects during treatment. This study explored the effects of medicarpin on depressive-li...
Presently, the regulatory mechanism underlying depression is indistinct, and almost 50% of depression sufferers undergo no apparent effects during treatment. This study explored the effects of medicarpin on depressive-like behaviors in a chronic unpredictable mild stress (CUMS)-induced mouse model of depression. The results of network pharmacological analysis revealed that liver X receptor β (LXRβ) might be a potential target of medicarpin and depression. The LXRβ level was reduced in the amygdala of mice induced by CUMS; however, this effect was suppressed by co-treatment with medicarpin. Medicarpin treatment ameliorated depressive-like behaviors in CUMS-induced mice by modulating LXRβ level. Moreover, medicarpin treatment reduced M1 polarization and enhanced M2 polarization of amygdala microglia in CUMS-induced mice, as well as increased GFAP level in the amygdala. Medicarpin treatment also suppressed CUMS-induced inflammation and hindered nuclear factor-κ B (NF-κB) signaling activation. These data indicate that medicarpin activated astrocytes and inhibited microglia M1 polarization while promoted M2 polarization by enhancing the expression of LXRβ. Hence, our results suggest that medicarpin could have a positive effect on the treatment of depression, and LXRβ could serve as a novel therapeutic target.
Neonatal Isoflurane Exposure in Rats Impairs Short-Term Memory, Cell Viability, and Glutamate Uptake in Slices of the Frontal Cerebral Cortex, But Not the Hippocampus, in Adulthood.
de Oliveira LF, Poluceno GG, Sampaio TB … +9 more , Constantino LC, Costa AP, Martins WC, Dal-Cim T, de Oliveira KA, Ludka FK, Prediger RD, Pereira FC, Tasca CI
Neurotox Res · 2022 Dec · PMID 36441450 · Publisher ↗
Neonatal exposure to general anesthetics has been associated with neurotoxicity and morphologic changes in the developing brain. Isoflurane is a volatile anesthetic widely used in pediatric patients to induce general ane...
Neonatal exposure to general anesthetics has been associated with neurotoxicity and morphologic changes in the developing brain. Isoflurane is a volatile anesthetic widely used in pediatric patients to induce general anesthesia, analgesia, and perioperative sedation. In the present study, we investigated the effects of a single neonatal isoflurane (3% in oxygen, 2 h) exposure in rats at postnatal day (PND) 7, in short-term (24 h - PND8) and long-term (adulthood) protocols. In PND8, ex vivo analysis of hippocampal and frontal cortex slices evaluated cell viability and susceptibility to in vitro glutamate challenge. In adult rats, behavioral parameters related to anxiety-like behavior, short-term memory, and locomotor activity (PND60-62) and ex vivo analysis of cell viability, membrane permeability, glutamate uptake, and susceptibility to in vitro glutamate challenge in hippocampal and cortical slices from PND65. A single isoflurane (3%, 2 h) exposure at PND7 did not acutely alter cell viability in cortical and hippocampal slices of infant rats (PND8) per se and did not alter slice susceptibility to in vitro glutamate challenge. In rat's adulthood, behavioral analysis revealed that the neonatal isoflurane exposure did not alter anxiety-like behavior and locomotor activity (open field and rotarod tests). However, isoflurane exposure impaired short-term memory evaluated in the novel object recognition task. Ex vivo analysis of brain slices showed isoflurane neonatal exposure selectively decreased cell viability and glutamate uptake in cortical slices, but it did not alter hippocampal slice viability or glutamate uptake (PND65). Isoflurane exposure did not alter in vitro glutamate-induced neurotoxicity to slices, and isoflurane exposure caused no significant long-term damage to cell membranes in hippocampal or cortical slices. These findings indicate that a single neonatal isoflurane exposure did not promote acute damage; however, it reduced cortical, but not hippocampal, slice viability and glutamate uptake in the adulthood. Additionally, behavioral analysis showed neonatal isoflurane exposure induces short-term recognition memory impairment, consolidating that neonatal exposure to volatile anesthetics may lead to behavioral impairment in the adulthood, although it may damage brain regions differentially.
COA-Cl Evokes Protective Responses Against HO-and 6-OHDA-Induced Toxic Injury in PC12 Cells.
Jamal M, Tsukamoto I, Maki T … +3 more , Takei S, Konishi R, Kinoshita H
Neurotox Res · 2022 Dec · PMID 36435924 · Publisher ↗
COA-Cl, a novel adenosine-like nucleic acid analog, has recently been shown to exert neuroprotective effects and to increase dopamine levels both in vivo and in vitro. Therefore, we hypothesized that COA-Cl could protect...
COA-Cl, a novel adenosine-like nucleic acid analog, has recently been shown to exert neuroprotective effects and to increase dopamine levels both in vivo and in vitro. Therefore, we hypothesized that COA-Cl could protect dopaminergic neurons against toxic insults. Thus, the present study aimed to investigate the protective effects of COA-Cl against hydrogen peroxide (HO)- and 6-hydroxydopamine (6-OHDA)-induced toxicity in PC12 cells and to elucidate the possible mechanisms. PC12 cells were incubated with COA-Cl (100 μM) with or without HO or 6-OHDA (200 μM) for 24 h. Treatment with COA-Cl attenuated the decrease in cell viability, SOD activity and the Bcl-2/Bax ratio caused by HO. In addition, COA-Cl attenuated the increase in LDH release, ROS production, caspase-3 activity, and apoptosis induced by HO. Further, COA-Cl enhanced the protection of PC12 cells against the toxicity caused by 6-OHDA, as evidenced by an increase in cell viability and the Bcl-2/Bax ratio, and a decrease in LDH release. Our results are the first to demonstrate that COA-Cl potentially protects PC12 cells against toxicity induced by HO and 6-OHDA, implying that COA-Cl could be a promising neuroprotective agent for the treatment of Parkinson's disease.
Biogenic Selenium Nanoparticles Attenuate Aβ-Induced Toxicity in PC12 Cells via Akt/CREB/BDNF Signaling Pathway.
Qiao L, Chen Y, Dou X … +2 more , Song X, Xu C
Neurotox Res · 2022 Dec · PMID 36435923 · Publisher ↗
Deposition of aggregated amyloid beta (Aβ) protein is considered to be a major causative factor that is associated with the development of oxidative stress and neuroinflammation in the pathogenesis of Alzheimer's disease...
Deposition of aggregated amyloid beta (Aβ) protein is considered to be a major causative factor that is associated with the development of oxidative stress and neuroinflammation in the pathogenesis of Alzheimer's disease (AD). Selenium nanoparticles (SeNPs) have been experimentally using for treatment of neurological disease due to their low toxicity, high bioavailability, and multiple bioactivities. This study was conducted to investigate the protective effects of biogenic SeNPs by Lactobacillus casei ATCC 393 against Aβ-induced toxicity in PC12 cells and its association with oxidative stress and inflammation. The results showed that SeNPs had no cytotoxicity on PC12 cells. Moreover, SeNPs entered cells through cellular endocytosis, which effectively attenuated Aβ-induced toxicity in PC12 cells. In addition, compared with Aβ model group, SeNP pretreatment significantly enhanced the antioxidant capacity, inhibited the overproduction of reactive oxygen species (ROS), effectively regulated the inflammatory response, decreased the activity of acetylcholinesterase, significantly reduced the expression level of caspase-1 and the ratio of Bcl-2/Bax, and upregulated the expression level of p53. Furthermore, compared with Aβ model group, SeNPs effectively promoted the phosphorylation of Akt and cAMP-response element-binding protein (CREB), and upregulated the expression level of brain-derived neurotrophic factor (BDNF). In addition, the Akt inhibitor (AKT inhibitor VIII, AKTi-1/2) could reverse the protective effects of SeNPs on PC12 cells. The Akt agonist (SC79) had a similar effect on PC12 cells as that of SeNPs. Overall, this study demonstrated that biogenic SeNPs can effectively alleviate the Aβ-induced toxicity in PC12 cells via Akt/CREB/BDNF signaling pathway.
Combined Exposure to Chronic Sleep Deprivation and Caffeine Potentiates Behavioural Deficits by Altering Neurochemical Profile and Synaptophysin Expression in Long-Evans Rats.
Edem EE, Okhonmina UE, Nebo KE … +5 more , Akinluyi ET, Ikuelogbon DA, Fafure AA, Olabiyi AA, Adedokun MA
Neurotox Res · 2022 Dec · PMID 36434357 · Publisher ↗
Using the Unpredictable Chronic Sleep Deprivation (UCSD) paradigm we developed, the combined effects of chronic sleep deprivation and high caffeine intake on prefrontal cortical synaptophysin expression, neurochemical pr...
Using the Unpredictable Chronic Sleep Deprivation (UCSD) paradigm we developed, the combined effects of chronic sleep deprivation and high caffeine intake on prefrontal cortical synaptophysin expression, neurochemical profiles, and behavioural outcomes in Long-Evans rats were evaluated. The combination of chronic sleep deprivation and high-dose caffeine treatment produced varying degrees of behavioural impairments, depletion of antioxidants, serotonin, and an upregulation of acetylcholinesterase (AChE) activity in the prefrontal cortex. An immunohistochemical assessment revealed a reduction in synaptophysin protein expression in the prefrontal cortex following exposure to high-dose caffeine and chronic sleep deprivation. Overall, our findings support the advocacy for adequate sleep for optimal mental performance as a high intake of caffeine to attenuate the effects of sleep deprivation that may alter the neurochemical profile and synaptic plasticity in the prefrontal cortex, significantly increasing the risk of neuropsychiatric/degenerative disorders.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe