Naringenin mitigates aluminum toxicity-induced learning memory impairments and neurodegeneration through amelioration of oxidative stress.

Aluminum chloride (AlCl3) is a potent neurotoxic substance known to cause memory impairment and oxidative stress-dependent neurodegeneration. Naringenin (NAR) is a dietary flavonoid with potent antioxidant and anti-inflammatory properties which was implemented against AlCl3-induced neurotoxicity to ascertain its neuroprotective efficacy. Experimental neurotoxicity in mice was induced by exposure of AlCl3 (10 mg/kg, p.o.) followed by treatment with NAR (10 mg/kg, p.o.) for a total of 63 days. Assessed the morphometric, learning memory dysfunction (novel object recognition, T- and Y-maze tests), neuronal oxidative stress, and histopathological alteration in different regions of the brain, mainly cortex, hippocampus, thalamus, and cerebellum. AlCl3 significantly suppressed the spatial learning and memory power which were notably improved by administration of NAR. The levels of oxidative stress parameters nitric oxide, advanced oxidation of protein products, protein carbonylation, lipid peroxidation, superoxide dismutase, catalase, glutathione reductase, reduced glutathione, and the activity of acetylcholine esterase were altered 1.5-3 folds by AlCl3 significantly. Treatment of NAR remarkably restored the level of oxidative stress parameters and maintained the antioxidant defense system. AlCl3 suppressed the expression of neuronal proliferation marker NeuN that was restored by NAR treatment which may be a plausible mechanism. NAR showed therapeutic efficacy as a natural supplement against aluminum-intoxicated memory impairments and histopathological alteration through a mechanism involving an antioxidant defense system and neuronal proliferation.

The changing of α5-GABAA receptors expression and distribution participate in sevoflurane-induced learning and memory impairment in young mice.

BACKGROUND: Sevoflurane is a superior agent for maintaining anesthesia during surgical procedures. However, the neurotoxic mechanisms of clinical concentration remain poorly understood. Sevoflurane can interfere with the normal function of neurons and synapses and impair cognitive function by acting on α5-GABAAR. METHODS: Using MWM test, we evaluated cognitive abilities in mice following 1 h of anesthesia with 2.7%-3% sevoflurane. Based on hippocampal transcriptome analysis, we analyzed the differential genes and IL-6 24 h post-anesthesia. Western blot and RT-PCR were performed to measure the levels of α5-GABAAR, Radixin, P-ERM, P-Radixin, Gephyrin, IL-6, and ROCK. The spatial distribution and expression of α5-GABAAR on neuronal somata were analyzed using histological and three-dimensional imaging techniques. RESULTS: MWM test indicated that partial long-term learning and memory impairment. Combining molecular biology and histological analysis, our studies have demonstrated that sevoflurane induces immunosuppression, characterized by reduced IL-6 expression levels, and that enhanced Radixin dephosphorylation undermines the microstructural stability of α5-GABAAR, leading to its dissociation from synaptic exterior and resulting in a disordered distribution in α5-GABAAR expression within neuronal cell bodies. On the synaptic cleft, the expression level of α5-GABAAR remained unchanged, the spatial distribution became more compact, with an increased fluorescence intensity per voxel. On the extra-synaptic space, the expression level of α5-GABAAR decreased within unchanged spatial distribution, accompanied by an increased fluorescence intensity per voxel. CONCLUSION: Dysregulated α5-GABAAR expression and distribution contributes to sevoflurane-induced partial long-term learning and memory impairment, which lays the foundation for elucidating the underlying mechanisms in future studies.

Bile acid metabolism is altered in learning and memory impairment induced by chronic lead exposure.

Lead is a neurotoxic contaminant that exists widely in the environment. Although lead neurotoxicity has been found to be tightly linked to gut microbiota disturbance, the effect of host metabolic disorders caused by gut microbiota disturbance on lead neurotoxicity has not been investigated. In this work, the results of new object recognition tests and Morris water maze tests showed that chronic low-dose lead exposure caused learning and memory dysfunction in mice. The results of 16 S rRNA sequencing of cecal contents and fecal microbiota transplantation showed that the neurotoxicity of lead could be transmitted through gut microbiota. The results of untargeted metabolomics and bile acid targeted metabolism analysis showed that the serum bile acid metabolism profile of lead-exposed mice was significantly changed. In addition, supplementation with TUDCA or INT-777 significantly alleviated chronic lead exposure-induced learning and memory impairment, primarily through inhibition of the NLRP3 inflammasome in the hippocampus to relieve neuroinflammation. In conclusion, our findings suggested that dysregulation of host bile acid metabolism may be one of the mechanisms of lead-induced neurotoxicity, and supplementation of specific bile acids may be a possible therapeutic strategy for lead-induced neurotoxicity.

Anthocyanins from blueberry ameliorated arsenic-induced memory impairment, oxidative stress, and mitochondrial-biosynthesis imbalance in rat hippocampal neurons.

In this study, blueberry anthocyanins extract (BAE) was used to investigate its protective effect on arsenic-induced rat hippocampal neurons damage. Arsenic exposure resulted in elevated levels of oxidative stress, decreased antioxidant capacity and increased apoptosis in rat hippocampal brain tissue and mitochondria. Immunohistochemical results showed that arsenic exposure also significantly decreased the expression of mitochondrial biosynthesis-related factors PGC-1α and TFAM. Treatment with BAE alleviated the decrease in antioxidant capacity, mitochondrial biogenesis related protein PGC-1α/NRF2/TFAM expression, and ATP production of arsenic induced hippocampal neurons in rats, and improved cognitive function in arsenic damaged rats. This study provides new insights into the detoxification effect of anthocyanins on the nervous system toxicity caused by metal exposure in the environment, indicating that anthocyanins may be a natural antioxidant against the nervous system toxicity caused by environmental metal exposure.

Dihydroergotamine Increases Histamine Brain Levels and Improves Memory in a Scopolamine-Induced Amnesia Model.

The beneficial effects of increasing histamine levels on memory have acquired special interest due to their applicability to psychiatric conditions that cause memory impairments. In addition, by employing drug repurposing approaches, it was demonstrated that dihydroergotamine (DHE), an FDA drug approved to treat migraines, inhibits Histamine N Methyl Transferase (HNMT), the enzyme responsible for the inactivation of histamine in the brain. For this reason, in the present work, the effect of DHE on histamine levels in the hippocampus and its effects on memory was evaluated, employing the scopolamine-induced amnesia model, the Novel Object Recognition (NOR) paradigm, and the Morris Water Maze (MWM). Furthermore, the role of histamine 1 receptor (H1R) and histamine 2 receptor (H2R) antagonists in the improvement in memory produced by DHE in the scopolamine-induced amnesia model was evaluated. Results showed that the rats that received DHE (10 mg/kg, i.p.) showed increased histamine levels in the hippocampus after 1 h of administration but not after 5 h. In behavioral assays, it was shown that DHE (1 mg/kg, i.p.) administered 20 min before the training reversed the memory impairment produced by the administration of scopolamine (2 mg/kg, i.p.) immediately after the training in the NOR paradigm and MWM. Additionally, the effects in memory produced by DHE were blocked by pre-treatment with pyrilamine (20 mg/kg, i.p.) administered 30 min before the training in the NOR paradigm and MWM. These findings allow us to demonstrate that DHE improves memory in a scopolamine-induced amnesia model through increasing histamine levels at the hippocampus due to its activity as an HNMT inhibitor.

A Novel Tetrapeptide Ala-Phe-Phe-Pro (AFFP) Derived from Antarctic Krill Prevents Scopolamine-Induced Memory Disorder by Balancing Lipid Metabolism of Mice Hippocampus.

Memory impairment is a serious problem with organismal aging and increased social pressure. The tetrapeptide Ala-Phe-Phe-Pro (AFFP) is a synthetic analogue of Antarctic krill derived from the memory-improving Antarctic krill peptide Ser-Ser-Asp-Ala-Phe-Phe-Pro-Phe-Arg (SSDAFFPFR) after digestion and absorption. The objective of this research was to assess the neuroprotective effects of AFFP by reducing oxidative stress and controlling lipid metabolism in the brains of mice with memory impairment caused by scopolamine. The 1H Nuclear magnetic resonance spectroscopy results showed that AFFP had three active hydrogen sites that could contribute to its antioxidant properties. The findings from in vivo tests demonstrated that AFFP greatly enhanced the mice's behavioral performance in the passive avoidance, novel object recognition, and eight-arm maze experiments. AFFP reduced oxidative stress by enhancing superoxide dismutase activity and malondialdehyde levels in mice serum, thereby decreasing reactive oxygen species level in the mice hippocampus. In addition, AFFP increased the unsaturated lipid content to balance the unsaturated lipid level against the neurotoxicity of the mice hippocampus. Our findings suggest that AFFP emerges as a potential dietary intervention for the prevention of memory impairment disorders.

Berberine and hesperidin prevent the memory consolidation impairment induced by pentylenetetrazole in zebrafish.

This study verified the effects of the natural compounds berberine and hesperidin on seizure development and cognitive impairment triggered by pentylenetetrazole (PTZ) in zebrafish. Adult animals were submitted to a training session in the inhibitory avoidance test and, after 10 minutes, they received an intraperitoneal injection of 25, 50, or 100 mg/kg berberine or 100 or 200 mg/kg hesperidin. After 30 minutes, the animals were exposed to 7.5 mM PTZ for 10 minutes. Animals were submitted to the test session 24 h after the training session to verify their cognitive performance. Zebrafish larvae were exposed to 100 µM or 500 µM berberine or 10 µM or 50 µM hesperidin for 30 minutes. After, larvae were exposed to PTZ and had the seizure development evaluated by latency to reach the seizure stages I, II, and III. Adult zebrafish pretreated with 50 mg/kg berberine showed a longer latency to reach stage III. Zebrafish larvae pretreated with 500 µM berberine showed a longer latency to reach stages II and III. Hesperidin did not show any effect on seizure development both in larvae and adult zebrafish. Berberine and hesperidin pretreatments prevented the memory consolidation impairment provoked by PTZ-induced seizures. There were no changes in the distance traveled in adult zebrafish pretreated with berberine or hesperidin. In larval stage, berberine caused no changes in the distance traveled; however, hesperidin increased the locomotion. Our results reinforce the need for investigating new therapeutic alternatives for epilepsy and its comorbidities.

The role of the cholinergic system in the memory-protecting effects of metformin in a model of scopolamine-induced memory impairment in aged rats.

PURPOSE: As the elderly population grows, the prevalence of dementia is also rapidly increasing worldwide. Metformin, an antidiabetic drug, has been shown to have ameliorative effects on impaired cognitive functions in experimental models. However, studies have generally used young animals. Additionally, although it has a major role in Alzheimer's disease (AD) and memory, literature information about the effects of metformin on the cholinergic system is limited. In this study, we investigated the effects of metformin on memory in a model of scopolamine-induced memory impairment in aged rats. We also examined the effects of metformin on the cholinergic system, which is very important in cognitive functions. METHODS: Metformin was administered orally to male Wistar rats (20-22 months old) at 100 mg/kg/day for three weeks. Morris water maze (MWM) tests were performed to assess spatial memory. Before the probe test of the MWM test, scopolamine was injected intraperitoneally at a dose of 1 mg/kg. After testing, animals were sacrificed, whole brains were removed, and hippocampus samples were separated for biochemical analysis. RESULTS: Impaired memory associated with scopolamine administration was reversed by metformin. In addition, metformin administration ameliorated scopolamine-induced changes in acetylcholine (ACh) levels, acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and choline acetyltransferase (ChAT) activity. CONCLUSION: Our results show that metformin may have protective effects in a scopolamine-induced memory impairment model in aged animals by improving cholinergic function. Metformin shows promise in preventing dementia with its dual cholinesterase inhibition and ChAT activation effect.

Histological and Memory Alterations in an Innovative Alzheimer's Disease Animal Model by Vanadium Pentoxide Inhalation.

Background: Previous work from our group has shown that chronic exposure to Vanadium pentoxide (V2O5) causes cytoskeletal alterations suggesting that V2O5 can interact with cytoskeletal proteins through polymerization and tyrosine phosphatases inhibition, causing Alzheimer's disease (AD)-like hippocampal cell death. Objective: This work aims to characterize an innovative AD experimental model through chronic V2O5 inhalation, analyzing the spatial memory alterations and the presence of neurofibrillary tangles (NFTs), amyloid-ß (Aß) senile plaques, cerebral amyloid angiopathy, and dendritic spine loss in AD-related brain structures. Methods: 20 male Wistar rats were divided into control (deionized water) and experimental (0.02 M V2O5 1 h, 3/week for 6 months) groups (n = 10). The T-maze test was used to assess spatial memory once a month. After 6 months, histological alterations of the frontal and entorhinal cortices, CA1, subiculum, and amygdala were analyzed by performing Congo red, Bielschowsky, and Golgi impregnation. Results: Cognitive results in the T-maze showed memory impairment from the third month of V2O5 inhalation. We also noted NFTs, Aß plaque accumulation in the vascular endothelium and pyramidal neurons, dendritic spine, and neuronal loss in all the analyzed structures, CA1 being the most affected. Conclusions: This model characterizes neurodegenerative changes specific to AD. Our model is compatible with Braak AD stage IV, which represents a moment where it is feasible to propose therapies that have a positive impact on stopping neuronal damage.

Synergistic suppression of BDNF via epigenetic mechanism deteriorating learning and memory impairment caused by Mn and Pb co-exposure.

Microglia, the resident immune cells of the central nervous system (CNS), play a dual role in neurotoxicity by releasing the NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome and brain-derived neurotrophic factor (BDNF) in response to environmental stress. Suppression of BDNF is implicated in learning and memory impairment induced by exposure to manganese (Mn) or lead (Pb) individually. Methyl CpG Binding Protein 2 (MeCp2) and its phosphorylation status are related to BDNF suppression. Protein phosphatase2A (PP2A), a member of the serine/threonine phosphatases family, dephosphorylates substrates based on the methylation state of its catalytic C subunit (PP2Ac). However, the specific impairment patterns and molecular mechanisms resulting from co-exposure to Mn and Pb remain unclear. Therefore, the purpose of this study was to explore the effects of Mn and Pb exposure, alone and in combination, on inducing neurotoxicity in the hippocampus of mice and BV2 cells, and to determine whether simultaneous exposure to both metals exacerbate their toxicity. Our findings reveal that co-exposure to Mn and Pb leads to severe learning and memory impairment in mice, which correlates with the accumulation of metals in the hippocampus and synergistic suppression of BDNF. This suppression is accompanied by up-regulation of the epigenetic repressor MeCp2 and its phosphorylation status, as well as demethylation of PP2Ac. Furthermore, inhibition of PP2Ac demethylation using ABL127, an inhibitor for its protein phosphatase methylesterase1 (PME1), or knockdown of MeCp2 via siRNA transfection in vitro effectively increases BDNF expression and mitigates BV2 cell damage induced by Mn and Pb co-exposure. We also observe abnormal activation of microglia characterized by enhanced release of the NLRP3 inflammasome, Casepase-1 and pro-inflammatory cytokines IL-1ß, in the hippocampus of mice and BV2 cells. In summary, our experiments demonstrate that simultaneous exposure to Mn and Pb results in more severe hippocampus-dependent learning and memory impairment, which is attributed to epigenetic suppression of BDNF mediated by PP2A regulation.

Suberoylanilide hydroxamic acid attenuates cognitive impairment in offspring caused by maternal surgery during mid-pregnancy.

Some pregnant women have to experience non-obstetric surgery during pregnancy under general anesthesia. Our previous studies showed that maternal exposure to sevoflurane, isoflurane, propofol, and ketamine causes cognitive deficits in offspring. Histone acetylation has been implicated in synaptic plasticity. Propofol is commonly used in non-obstetric procedures on pregnant women. Previous studies in our laboratory showed that maternal propofol exposure in pregnancy impairs learning and memory in offspring by disturbing histone acetylation. The present study aims to investigate whether HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) could attenuate learning and memory deficits in offspring caused by maternal surgery under propofol anesthesia during mid-pregnancy. Maternal rats were exposed to propofol or underwent abdominal surgery under propofol anesthesia during middle pregnancy. The learning and memory abilities of the offspring rats were assessed using the Morris water maze (MWM) test. The protein levels of histone deacetylase 2 (HDAC2), phosphorylated cAMP response-element binding (p-CREB), brain-derived neurotrophic factor (BDNF), and phosphorylated tyrosine kinase B (p-TrkB) in the hippocampus of the offspring rats were evaluated by immunofluorescence staining and western blot. Hippocampal neuroapoptosis was detected by TUNEL staining. Our results showed that maternal propofol exposure during middle pregnancy impaired the water-maze learning and memory of the offspring rats, increased the protein level of HDAC2 and reduced the protein levels of p-CREB, BDNF and p-TrkB in the hippocampus of the offspring, and such effects were exacerbated by surgery. SAHA alleviated the cognitive dysfunction and rescued the changes in the protein levels of p-CREB, BDNF and p-TrkB induced by maternal propofol exposure alone or maternal propofol exposure plus surgery. Therefore, SAHA could be a potential and promising agent for treating the learning and memory deficits in offspring caused by maternal nonobstetric surgery under propofol anesthesia.

Marrubium vulgare Extract Improves Spatial Working Memory and Oxidative Stress Damage in Scopolamine-Treated Rats.

Background: The cholinergic neuronal loss in the basal forebrain and increasing brain oxidative stress are one of the main features of the brain suffering from Alzheimer's disease. Marrubium vulgare (M. vulgare), commonly known as 'white horehound,' possesses a variety of valuable properties, such as antioxidative, anti-inflammatory, and antidiabetic activities. Moreover, it possesses neuromodulatory properties that could potentially impact short-term memory functions. Objective: The present study was undertaken to investigate the preventive effects of water M. vulgare extract on working memory, cholinergic neurotransmission, and oxidative stress in rats with scopolamine (Sco)-induced dementia. Methods: Male Wistar rats (200-250 g) were divided into four experimental groups. The plant extract was administered orally for 21 days, and Sco (2 mg/kg) was administered intraperitoneally for 11 consecutive days. The behavioral performance of the animals was evaluated by the T-maze test. The effect of the extract on acetylcholinesterase (AChE) activity and antioxidant status in cortex and hippocampus were also monitored. Results: Our experimental data revealed that treatment with M. vulgare significantly increased the percentage of correct choices of rats with Sco-induced dementia in the T maze test (by 38%, p < 0.05). Additionally, it reduced AChE activity in the hippocampus (by 20%, p < 0.05) and alleviated oxidative stress induced by Sco, particularly in the cortex. Conclusions: M. vulgare water extract demonstrated working memory preserving effect in rats with Sco-induced dementia, AChE inhibitory activity and in vivo antioxidant potential, and deserve further attention.

Butin attenuates behavioral disorders via cholinergic/BDNF/Caspase-3 pathway in scopolamine-evoked memory deficits in rats.

OBJECTIVE: Recent research suggests that butin may also exert neuroprotective effects. However, its influence on cognitive performance and, specifically, its potential to mitigate scopolamine-induced memory impairment remains unexplored. The aim of the study is to investigate the effects of butin on the cognitive and behavioral performance of rats with scopolamine-induced memory impairment. MATERIALS AND METHODS: Scopolamine-injected memory-impediment model in rats was used to determine the efficacy of butin in higher and lower doses (10 and 20 mg/kg) for 14 days. Y-maze, along with Morris water, was used to assess the ability to recall spatial and working information. Biochemistry-related functions such as acetylcholinesterase, choline acetyltransferase, superoxide dismutase, glutathione transferase, malonaldehyde, catalase, nitric oxide, and neurotransmitters levels were estimated as indicators of free radical damage. Furthermore, we evaluated neuro-inflammatory responses by assessing tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF) and caspase-3 immuno-reactive proteins. RESULTS: When assessed through behavioral paradigms, the butin-treated group enhanced the spatial and working memory of rodents. Scopolamine caused a substantial alteration in biochemical-related parameters, neuronal enzymatic, inflammation responses and apoptosis markers prominently restored by butin. CONCLUSIONS: This study concludes that butin protects scopolamine-injected rats from behavioral impairments and neuronal damage by reducing apoptosis and neuroinflammation.

Pretreatment with Liposome-Encapsulated Shrimp Shell Extract Attenuated Neuronal Damage and Death in Aß1-42-Induced Memory Deficits in Rats.

The accumulation of amyloid-beta (Aß) peptides is a crucial factor in the neuronal degeneration of Alzheimer's disease (AD). The current study investigated the underlying neuroprotective mechanisms of shrimp shell extract (SSE) and liposome-encapsulated SSE (SSE/L) against Aß1-42-induced neuronal damage and death in rats. Intracerebroventricular infusion of Aß1-42 effectively induced memory decline, as observed in a reduction of the rat's discriminating ability in the novel object recognition and novel object location tasks. Oral pretreatment with 100 mg/kg of SSE demonstrated no preventive effect on the memory decline induced by Aß1-42 infusion. However, treatment with SSE/L 100 mg/kg BW effectively attenuated memory deficits in both behavioral assessments following two and four weeks after Aß1-42 infusion. Moreover, SSE/L exerted neuroprotective effects by reducing lipid peroxidation and increasing Nrf2/HO-1 expression. There was a significant decrease in Iba1 and GFAP (biomarkers of microglia and astrocyte activity, respectively), as well as a decrease in the levels of NF-κB expression and the inflammatory cytokines TNF-α and IL-6 in the cortical and hippocampal tissues. Treatment with SSE/L also reduced the pro-apoptotic proteins Bax and cleaved caspase-3 while raising the anti-apoptotic protein Bcl2. In addition, the beneficial effects of SSE/L were along with the effects of a positive control commercial astaxanthin (AST). The findings of this study indicated that SSE/L provided neuroprotective effects on Aß1-42-induced AD rats by ameliorating oxidative stress, neuroinflammation and apoptotic cell death. Therefore, SSE/L might be employed to prevent and mitigate Aß accumulation-induced neurotoxicity in AD.

MM165 - A Small Hybrid Molecule Modulates the Kynurenine Pathway and Attenuates Lipopolysaccharide-Induced Memory Deficits and Inflammation.

Cognitive dysfunctions are now recognized as core symptoms of various psychiatric disorders e.g., major depressive disorder. Sustained immune activation may leads to cognitive dysfunctions. Proinflammatory cytokines shunt the metabolism of tryptophan towards kynurenine and quinolinic acid may accumulate at toxic concentrations. This acid triggers an increase in neuronal nitric oxide synthase function and promotes oxidative stress. The searching for small molecules that can regulate tryptophan metabolites produced in the kynurenic pathway has become an important goal in developing treatments for various central nervous system diseases with an inflammatory component. Previously we have identified a small hybrid molecule - MM165 which significantly reduces depressive-like symptoms caused by inflammation induced by lipopolysaccharide administration. In the present study, we investigated whether this compound would mitigate cognitive deficits induced by lipopolysaccharide administration and whether treatment with it would affect the plasma or brain levels of quinolinic acid and kynurenic acid. Neuroinflammation was induced in rats by administering lipopolysaccharide at a dose of 0.5 mg/kg body weight for 10 days. We conducted two tests: novel object recognition and object location, to assess the effect on memory impairment in animals previously treated with lipopolysaccharide. In plasma collected from rats, the concentrations of C-reactive protein and tumor necrosis factor alfa were determined. The concentrations of kynurenic acid and quinolinic acid were determined in plasma and homogenates obtained from the cerebral cortex of rats. Interleukin 6 in the cerebral cortex of rats was determined. Additionally, the body and spleen mass and spontaneous activity were measured in rats. Our study shows that MM165 may mitigate cognitive deficits induced by inflammation after administration of lipopolysaccharide and alter the concentrations of tryptophan metabolites in the brain. Compounds exhibiting a mechanism of action analogous to that of MM165 may serve as foundational structures for the development of a new class of antidepressants.

Toxic encephalopathy, vision loss, and memory disorder caused by acute acrylamide exposure.

Acrylamide (ACR) is an irritant that can cause damage to the eyes, skin, and nervous and reproductive systems. This study aims to illustrate a case of central nervous system and optic nerve damage from exposure to ACR. In this case, a 49-year-old male material handler was accidentally splashed with ACR solution on both of his upper limbs. Consequently, he was admitted to the hospital with toxic encephalopathy, characterized by cerebellar ataxia and slurred speech. Magnetic resonance imaging scan, a brain computed tomography scan blood sample analyses, optic coherence tomography, electroneuromyogram, and visual evoked potentials examination were performed. After 20 days of receiving symptomatic support treatment, the patient continued to experience disturbances in consciousness. Then, he developed vision loss, memory disorders, and symptoms of peripheral neuropathy such as skin peeling, extremity weakness, and absent tendon reflexes. This case report underscores the severe consequences of acute dermal exposure to high concentrations of ACR, resulting in toxic encephalopathy, visual impairment, and memory disorders, which will contribute to a broader understanding of ACR toxicity.

Regulation mechanisms of sea cucumber peptides against scopolamine-induced memory disorder and novel memory-improving peptides identification.

Memory impairment affects cognition and information processing, and attention, leading to a decline in life quality of patients. Previous studies have shown the memory-improving effects of sea cucumber peptides. This study further explored the memory-improving mechanisms of sea cucumber peptides using scopolamine-induced memory-impaired mice and identified novel memory-improving peptides within low molecular weight peptide fractions. The sea cucumber peptides were categorized into three groups based on their molecular weights: SCP-L (molecular weight greater than 10 kDa), SCP-M (weight between 3 kDa and 10 kDa), and SCP-S (molecular weight less than 3 kDa). The results showed that SCP-S improved behavioral performance by regulating cholinergic system disorder and reducing oxidative stress levels, distinguishing itself from SCP-M and SCP-L. Further, SCP-S was found to exhibit a well ability in alleviating the degree of neuroinflammation dependent on microglia and promoting synaptic plasticity. Additionally, a novel memory-improving peptide Ser-Phe-Gly-Asp-Ile (SFGDI) was identified by EASY-nano-LC/MS/MS after simulated digestion-absorption coupling of in silico technologies from SCP-S. SFGDI protected against oxidative stress and regulated cholinergic system in scopolamine-induced PC12 cells. These findings suggest that SCP-S and SFGDI might be considered as potential memory-improving food for people suffering from memory disorders.

Futoquinol improves Aß25-35-induced memory impairment in mice by inhibiting the activation of p38MAPK through the glycolysis pathway and regulating the composition of the gut microbiota.

Futoquinol (Fut) is a compound extracted from Piper kadsura that has a nerve cell protection effect. However, it is unclear whether Fut has protective effects in Alzheimer's disease (AD). In this study, we aimed to explore the therapeutic effect of Fut in AD and its underlying mechanism. UPLC-MS/MS method was performed to quantify Fut in the hippocampus of mice brain. The cognition ability, neuronal and mitochondria damage, and levels of Aß1-42, Aß1-40, p-Tau, oxidative stress, apoptosis, immune cells, and inflammatory factors were measured in Aß25-35-induced mice. The content of bacterial meta-geometry was predicted in the microbial composition based on 16S rDNA. The protein levels of HK II, p-p38MAPK, and p38MAPK were detected. PC-12 cells were cultured in vitro, and glucose was added to activate glycolysis to further explore the mechanism of action of Fut intervention in AD. Fut improved the memory and learning ability of Aß25-35 mice, and reduced neuronal damage and the deposition of Aß and Tau proteins. Moreover, Fut reduced mitochondrial damage, the levels of oxidative stress, apoptosis, and inflammatory factors. Fut significantly inhibited the expression of HK II and p-p38MAPK proteins. The in vitro experiment showed that p38MAPK was activated and Fut action inhibited after adding 10 mM glucose. Fut might inhibit the activation of p38MAPK through the glycolysis pathway, thereby reducing oxidative stress, apoptosis, and inflammatory factors and improving Aß25-35-induced memory impairment in mice. These data provide pharmacological rationale for Fut in the treatment of AD.

The decanoate esters of nandrolone, testosterone, and trenbolone induce steroid specific memory impairment and somatic effects in the male rat.

Long-term use of anabolic androgenic steroids (AAS) in supratherapeutic doses is associated with severe adverse effects, including physical, mental, and behavioral alterations. When used for recreational purposes several AAS are often combined, and in scientific studies of the physiological impact of AAS either a single compound or a cocktail of several steroids is often used. Because of this, steroid-specific effects have been difficult to define and are not fully elucidated. The present study used male Wistar rats to evaluate potential somatic and behavioral effects of three different AAS; the decanoate esters of nandrolone, testosterone, and trenbolone. The rats were exposed to 15 mg/kg of nandrolone decanoate, testosterone decanoate, or trenbolone decanoate every third day for 24 days. Body weight gain and organ weights (thymus, liver, kidney, testis, and heart) were measured together with the corticosterone plasma levels. Behavioral effects were studied in the novel object recognition-test (NOR-test) and the multivariate concentric square field-test (MCSF-test). The results conclude that nandrolone decanoate, but neither testosterone decanoate nor trenbolone decanoate, caused impaired recognition memory in the NOR-test, indicating an altered cognitive function. The behavioral profile and stress hormone level of the rats were not affected by the AAS treatments. Furthermore, the study revealed diverse AAS-induced somatic effects i.e., reduced body weight development and changes in organ weights. Of the three AAS included in the study, nandrolone decanoate was identified to cause the most prominent impact on the male rat, as it affected body weight development, the weights of multiple organs, and caused an impaired memory function.

Sodium butyrate alleviates lead-induced neuroinflammation and improves cognitive and memory impairment through the ACSS2/H3K9ac/BDNF pathway.

Lead is an environmentally widespread neurotoxic pollutant. Although the neurotoxicity of lead has been found to be closely associated with metabolic disorders, the effects of short-chain fatty acids on the neurotoxicity of lead and its mechanisms have not yet been explored. In this study, the results of open field tests and Morris water maze tests demonstrated that chronic lead exposure caused learning and memory deficits and anxiety-like symptoms in mice. The serum butyric acid content of lead-treated mice decreased in a dose-dependent manner, and oral administration of butyrate significantly improved cognitive memory impairment and anxiety symptoms in lead-exposed mice. Moreover, butyrate alleviated neuroinflammation caused by lead exposure by inhibiting the STAT3 signaling in microglia. Butyrate also promoted the expression of acetyl-CoA synthetase ACSS2 in hippocampal neurons, thereby increasing the content of acetyl-CoA and restoring the expression of both histone H3K9ac and the downstream BDNF. We also found that the median butyric acid concentration in high-lead exposure humans was remarkably lower than that in the low-lead exposure humans (45.16 µg/L vs. 60.92 µg/L, P < 0.01), and that butyric acid significantly mediated the relationship of lead exposure with the Montreal cognitive assessment scores, with a contribution rate of 27.57 %. In conclusion, our results suggest that butyrate supplementation is a possible therapeutic strategy for lead-induced neurotoxicity.