The Impact of Kundalini Yoga on Cognitive Function and Memory: A Systematic Review of Randomized Controlled Trials.

Cognitive decline and dementia are significant public health challenges influenced by various modifiable and non-modifiable risk factors. Kundalini yoga (KY) has emerged as a promising non-pharmacological intervention to enhance cognitive function and memory in older adults at risk of cognitive decline. This systematic review aims to evaluate the effects of KY on cognitive function, memory impairment, and related neurobiological and psychological outcomes in older adults. A comprehensive literature search was conducted across PubMed, MEDLINE, Scopus, Web of Science, and the Cochrane Library, covering studies published from January 2000 to December 2023. Randomised controlled trials (RCTs) were included to compare KY with other cognitive enhancement strategies, such as memory enhancement training (MET) and psychoeducation. Five RCTs with 215 participants met the inclusion criteria. The studies varied in sample size (11 to 81 participants) and duration (12 to 24 weeks). The participants were older adults (≥55 years) with mild cognitive impairment (MCI) or subjective cognitive decline (SCD). The interventions compared KY with MET or psychoeducation. KY consistently improved memory performance and executive function. Significant mood enhancements, increased hippocampal volume, and better neural connectivity were observed. KY also reduced pro-inflammatory cytokines and altered ageing-related gene expression, demonstrating both cognitive and neurobiological benefits. KY appears to be a promising intervention for enhancing cognitive function, mood, and neurobiological health in older adults at risk of cognitive decline and dementia. While further research with more extensive, well-designed RCTs is needed to confirm these findings and optimise intervention strategies, the existing evidence supports the integration of KY into cognitive health programmes. Practitioners should ensure proper training and gradual progression to maximise benefits and minimise risks.

Trends in memory function and memory impairment among older adults in the USA and Europe, 1996-2018.

BACKGROUND: Single-country studies document varying time trends in memory function and impairment. Comparative analyses are limited. METHODS: We used self-respondent data on adults aged 50+ years in 13 countries from three surveys (USA: HRS, 1998-2018; England: ELSA, 2002-2018; 11 European countries: SHARE, 2004-2019). Memory is measured with tests of immediate and delayed word recall. Unweighted age- and gender-adjusted mixed effects regression models as well as models with adjustments for additional socio-demographic characteristics and health behaviors were examined. Heterogeneity in trends by gender, age group, and educational attainment were measured. RESULTS: The age-adjusted 10-year improvement in average test score is 0.04 standard deviations (SDs) (95% confidence interval (CI): 0.03, 0.05) in the USA, 0.17 SDs (95% CI: 0.15, 0.19) in England, and 0.24 SDs (95% CI: 0.23, 0.25) in SHARE countries. Trends are largely similar across gender, age groups, and educational attainment. Regional differences in trends remain after adjustment for potential mechanisms. Difference between the USA and other countries is particularly large under aged 75 years compared to over aged 75 years. CONCLUSIONS: Pace of improvement in memory function varies strongly across countries. On average, the 11 European countries studied had the fastest improvement, followed by England. The trend in the USA indicates improvement, but at a much slower pace compared to that in England and other European countries. Uncovering the causes for the cross-country heterogeneity in time trends, and in particular the reasons for the comparatively poor performance of the USA, should be both a research and public health priority.

Hyperexcitation of the glutamatergic neurons in lateral hypothalamus induced by chronic pain contributes to depression-like behavior and learning and memory impairment in male mice.

Chronic pain can induce mood disorders and cognitive dysfunctions, such as anxiety, depression, and learning and memory impairment in humans. However, the specific neural network involved in anxiety- and depression-like behaviors and learning and memory impairment caused by chronic pain remains poorly understood. In this study, behavioral test results showed that chronic pain induced anxiety- and depression-like behaviors, and learning and memory impairment in male mice. c-Fos immunofluorescence and fiber photometry recording showed that glutamatergic neurons in the LH of mice with chronic pain were selectively activated. Next, the glutamatergic neurons of LH in normal mice were activated using optogenetic and chemogenetic methods, which recapitulates some of the depressive-like behaviors, as well as memory impairment, but not anxiety-like behavior. Finally, inhibition of glutamatergic neurons in the LH of mice with chronic pain, effectively relieved anxiety- and depression-like behaviors and learning and memory impairment. Taken together, our findings suggest that hyperexcitation of glutamatergic neurons in the LH is involved in depression-like behavior and learning and memory impairment induced by chronic pain.

Spontaneous cerebrovascular reactivity at rest in older adults with and without mild cognitive impairment and memory deficits.

Background: Older adults with mild cognitive impairment (MCI) exhibit deficits in cerebrovascular reactivity (CVR), suggesting CVR is a biomarker for vascular contributions to MCI. This study examined if spontaneous CVR is associated with MCI and memory impairment. Methods: 161 older adults free of dementia or major neurological/psychiatric disorders were recruited. Participants underwent clinical interviews, cognitive testing, venipuncture for Alzheimer's biomarkers, and brain MRI. Spontaneous CVR was quantified during 5 minutes of rest. Results: Whole brain CVR was negatively associated with age, but not MCI. Lower CVR in the parahippocampal gyrus (PHG) was found in participants with MCI and was linked to worse memory performance on memory tests. Results remained significant after adjusting for Alzheimer's biomarkers and vascular risk factors. Conclusion: Spontaneous CVR deficits in the PHG are observed in older adults with MCI and memory impairment, indicating medial temporal microvascular dysfunction's role in cognitive decline.

The Shape Trail Test Is Sensitive in Differentiating Older Adults with Mild Cognitive Impairment: A Culture-neutral Five-minute Test.

INTRODUCTION: The Shape Trail Test (STT) was developed based upon the Trail Making Test, as a culture-neutral test for measuring processing speed and mental flexibility. This study aims to evaluate the accuracy and validity of this five-minute test for differentiating individuals with normal cognition (NC), subjective memory impairment (SMI), and mild cognitive impairment (MCI). METHOD: The study included 210 participants aged 50-80 years, with 70 participants in each group matched for age, education, and gender. RESULTS: No significant difference in STT measures was found between the NC and SMI groups. In contrast, both the NC and SMI groups exhibited significantly better performance (shorter completion time in STT-A and STT-B and fewer STT-B errors) than the MCI group. No significant group differences were found in STT-A errors. Stepwise regression analysis identified three significant predictors for classifying the MCI group from the NC and/or SMI groups, including the STT-B completion time, the STT-A errors, and the interaction between STT-B completion time and STT-B errors. The composite score of these three predictors demonstrated good discriminatory power for classifying the MCI group from the other groups, with area under the curves (AUCs) of 0.76 - 0.79 (p < 0.001), sensitivities of 78.6% - 80%, and specificities of 60% - 61.4%. However, none of the STT measures or their interactions were significant predictors for differentiating the SMI group from the NC group. Besides, the STT measures were significantly correlated with age, education, and executive function measures. DISCUSSION: The STT could be a culture- and language-free, reliable test for assessing executive function and a sensitive test for predicting MCI.

Ameliorative effect of vanillic acid against scopolamine-induced learning and memory impairment in rat via attenuation of oxidative stress and dysfunctional synaptic plasticity.

Alzheimer's disease (AD) is characterized by cognitive impairment, loss of learning and memory, and abnormal behaviors. Scopolamine (SCOP) is a non-selective antagonist of muscarinic acetylcholine receptors that exhibits the behavioral and molecular hallmarks of AD. Vanillic acid (VA), a phenolic compound, is obtained from the roots of a traditional plant called Angelica sinensis, and has several pharmacologic effects, including antimicrobial, anti-inflammatory, anti-angiogenic, anti-metastatic, and antioxidant properties. Nevertheless, VA's neuroprotective potential associated with the memory has not been thoroughly investigated. Therefore, this study investigated whether VA treatment has an ameliorative effect on the learning and memory impairment induced by SCOP in rats. Behavioral experiments were utilized to assess the learning and memory performance associated with the hippocampus. Using western blotting analysis and assay kits, the neuronal damage, oxidative stress, and acetylcholinesterase activity responses of hippocampus were evaluated. Additionally, the measurement of long-term potentiation was used to determine the function of synaptic plasticity in organotypic hippocampal slice cultures. In addition, the synaptic vesicles' density and the length and width of the postsynaptic density were evaluated using electron microscopy. Consequently, the behavioral, biochemical, electrophysiological, and ultrastructural analyses revealed that VA treatment prevents learning and memory impairments caused by SCOP in rats. The study's findings suggest that VA has a neuroprotective effect on SCOP-induced learning and memory impairment linked to the hippocampal cholinergic system, oxidative damage, and synaptic plasticity. Therefore, VA may be a prospective therapeutic agent for treating AD.

The impact of reward and punishment sensitivity on memory and executive performance in individuals with amnestic mild cognitive impairment.

Amnestic mild cognitive impairment (aMCI) is defined by memory impairment but executive function (EF) deficits could be also a common feature. This study examined the underlying neurocognitive processes associated with executive function (EF) deficits in patients with aMCI using the Wisconsin Card Sorting Test (WCST) and computational modeling. Forty-two patients with aMCI and thirty-eight matched Controls performed the WSCT and underwent neurocognitive assessment. The Attentional Learning Model was applied the WCST. Patients with aMCI demonstrated deficits in feedback-learning. More specifically, patients showed increased Reward-Sensitivity and reduced Punishment-Sensitivity. These alterations were associated with poor WSCT performance and deficits in EF and Memory. Goal-directed deficits in aMCI, as observed in the WCST, are associated with difficulties in updating attention after feedback as its changes too rapidly following positive feedback and too slowly following negative feedback. Consequently, memory and EF deficits interact and reinforce each other generating performance deficits in patients with aMCI.

Efficacy and Safety of Panax ginseng Sprout Extract in Subjective Memory Impairment: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Sprout ginseng extract (ThinkGIN™) manufactured through a smart farm system has been shown to improve memory in preclinical studies. This study conducted a 12-week randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of ThinkGIN™ for improving memory in subjective memory impairment (SMI). Subjects aged 55 to 75 years with SMI participated in this study. A total of 80 subjects who met the inclusion/exclusion criteria were assigned to the ThinkGIN™ group (n = 40, 450 mg ThinkGIN™/day) or a placebo group (n = 40). Efficacy and safety evaluations were conducted before intervention and at 12 weeks after intervention. As a result of 12 weeks of ThinkGIN™ intake, significant differences in SVLT, RCFT, MoCA-K, PSQI-K, and AChE were observed between the two groups. Safety evaluation (AEs, laboratory tests, vital signs, and electrocardiogram) revealed that ThinkGIN™ was safe with no clinically significant changes. Therefore, ThinkGIN™ has the potential to be used as a functional food to improve memory.

Screening of active components of Ganoderma lucidum and decipher its molecular mechanism to improve learning and memory disorders.

Learning and memory impairment (LMI), a common degenerative central nervous system disease. Recently, more and more studies have shown that Ganoderma lucidum (GL) can improve the symptoms of LMI. The active ingredients in GL and their corresponding targets were screened through TCMSP (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform) and BATMAN-TCM (Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine) databases, and the potential LMI targets were searched for through GeneCard (GeneCards Human Gene Database) and DrugBank. Then, we construct a "main active ingredient-target" network and a protein-protein interaction (PPI) network diagram.The GO (Gene Ontology) functional enrichment analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway annotation analysis were performed on the common targets through DAVID (Database for Annotation Visualization and Integrated Discovery) to clarify the potential molecular mechanism of action of active ingredients in GL. The TNF protein was verified by western blot;Twenty one active ingredients in GL and 142 corresponding targets  were screened out, including 59 targets shared with LMI. The 448 biological processes shown by the GO functional annotation results and 55 signal pathways shown by KEGG enrichment analysis were related to the improvement of LMI by GL, among which the correlation of Alzheimer disease pathway is the highest, and TNF was the most important protein; TNF can improve LMI.GL can improve LMI mainly by 10 active ingredients in it, and they may play a role by regulating Alzheimer disease pathway and TNF protein.

Luteolin for neurodegenerative diseases: a review.

Neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and multiple sclerosis affect millions of people around the world. In addition to age, which is a key factor contributing to the development of all neurodegenerative diseases, genetic and environmental components are also important risk factors. Current methods of treating neurodegenerative diseases are mostly symptomatic and do not eliminate the cause of the disease. Many studies focus on searching for natural substances with neuroprotective properties that could be used as an adjuvant therapy in the inhibition of the neurodegeneration process. These compounds include flavonoids, such as luteolin, showing significant anti-inflammatory, antioxidant, and neuroprotective activity. Increasing evidence suggests that luteolin may confer protection against neurodegeneration. In this review, we summarize the scientific reports from preclinical in vitro and in vivo studies regarding the beneficial effects of luteolin in neurodegenerative diseases. Luteolin was studied most extensively in various models of Alzheimer's disease but there are also several reports showing its neuroprotective effects in models of Parkinson's disease. Though very limited, studies on possible protective effects of luteolin against Huntington's disease and multiple sclerosis are also discussed here. Overall, although preclinical studies show the potential benefits of luteolin in neurodegenerative disorders, clinical evidence on its therapeutic efficacy is still deficient.

Four-Dimensional Label-Free Quantitative Proteomics of Ginsenoside Rg2 Ameliorated Scopolamine-Induced Memory Impairment in Mice through the Lysosomal Pathway.

Alzheimer's disease (AD) is a neurodegenerative disease. Ginsenoside Rg2 has shown potential in treating AD, but the underlying protein regulatory mechanisms associated with ginsenoside Rg2 treatment for AD remain unclear. This study utilized scopolamine to induce memory impairment in mice, and proteomics methods were employed to investigate the potential molecular mechanism of ginsenoside Rg2 in treating AD model mice. The Morris water maze, hematoxylin and eosin staining, and Nissl staining results indicated that ginsenoside Rg2 enhanced cognitive ability and decreased neuronal damage in AD mice. Proteomics, western blot, and immunofluorescence results showed that ginsenoside Rg2 primarily improved AD mice by downregulating the expression of LGMN, LAMP1, and PSAP proteins through the regulation of the lysosomal pathway. Transmission electron microscopy and network pharmacology prediction results showed a potential connection between the mechanism of ginsenoside Rg2 treatment for AD mice and lysosomes. The comprehensive results indicated that ginsenoside Rg2 may improve AD by downregulating LGMN, LAMP1, and PSAP through the regulation of the lysosomal pathway.

Regulating effect of Qifu Yin on intestinal microbiota in mice with memory impairment induced by scopolamine hydrobromide.

ETHNOPHARMACOLOGICAL RELEVANCE: Qifu Yin (QFY) originates from "Jingyue Quanshu · Volume 51 · New Fang Bazhen · Buzhen" a work by Zhang Jingyue, a distinguished Chinese medical practitioner from the Ming Dynasty. QFY is composed of Ginseng Radix et Rhizoma, Rehmanniae Radix Praeparata, Angelicae Sinensis Radix, Atractylodis Macrocephalae Rhizoma, Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle, Ziziphi Spinosae Semen, and Polygalae Radix. QFY is frequently employed to address memory loss and cognitive impairment stemming from vascular dementia, Alzheimer's disease (AD), and related conditions. Our findings indicate that QFY can mitigate nerve cell damage. Moreover, the study explores the impact of QFY on the calcium ion pathway and sphingolipid metabolism in mice with myocardial infarction, presenting a novel perspective on QFY's mechanism in ameliorating myocardial infarction through lipidomics. While this research provides an experimental foundation for the clinical application of QFY, a comprehensive and in-depth analysis of its improvement mechanism remains imperative. AIM OF THE STUDY: To clarify the regulatory mechanism of QFY on intestinal microecology in mice with memory impairment (MI). MATERIAL AND METHODS: The memory impairment mouse model was established by intraperitoneal injection of scopolamine hydrobromide. Kunming (KM) mice were randomly divided into blank group, Ginkgo tablet group (0.276 g/kg), QFY high, medium and low dose groups (17.2 g/kg, 8.6 g/kg, 4.3 g/kg). The effect on memory ability was evaluated by open field and step-down behavioral experiments. The morphological changes of nerve cells in the hippocampus of mice were observed by pathological method. The contents of superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT) and glutathione peroxidase (GSH-Px) in the brain tissue of mice were detected. The expression levels of CREB, Brain-Derived Neurotrophic Factor (BDNF) and Recombinant Amyloid Precursor Protein (APP) in the hippocampus of mice were determined using immunohistochemistry. The expression of N-methyl-D-aspartate receptor (NMDAR) and cAMP response element binding protein (CREB) related factors in the serum of mice was analyzed by ELISA. The levels of apoptosis signal-regulating kinase-1 (ASK1) and c-Jun N-terminal kinase (JNK) mRNA in the hippocampus were detected by quantitative real-time fluorescence polymerase chain reaction (qPCR). The intestinal feces of mice were collected, and the 16 S rDNA technology was used to detect the changes in intestinal microbiota microecological structure of feces in each group. RESULTS: Behavioral experiments showed that the high-dose QFY group exhibited a significant increase in exercise time (P<0.05) and a decrease in diagonal time (P<0.05) compared to the model group. The medium-dose group of QFY showed a reduction in diagonal time (P<0.05). Additionally, the latency time significantly increased in the medium and high-dose groups of QFY (P<0.01). The number of errors in the low, medium and high dose groups was significantly decreased (P<0.05, P<0.01, P<0.01). The nerve cells in the CA1 and CA3 regions of QFY-treated mice demonstrated close arrangement and clear structure. Furthermore, the content of SOD significantly increased (P<0.01) and the content of MDA significantly decreased (P<0.05) in the low and high-dose QFY groups. The content of CAT in the medium-dose group significantly increased (P < 0.05). Immunohistochemical analysis showed a significant reduction in the number of APP expression particles in the CA1 and CA3 regions of all QFY groups. Moreover, BDNF expression significantly increased in the medium and high-dose groups, while CREB expression significantly increased in the low and medium-dose groups of QFY within the CA1 and CA3 regions. Serum analysis revealed significant increases in CREB content in the low, medium, and high dose groups of QFY (P<0.01, P<0.05, P<0.05), and decreases in NMDAR content across all QFY dose groups (P<0.01). PCR analysis showed a significant decrease in the contents of ASK1 and JNK in the medium-dose group (P<0.01). Microecological analysis of intestinal microbiota demonstrated a significant restoration trend in the relative abundance of Fusobacteria, Planctomycetes, and Verrucomicrobia (P<0.01 or P<0.05) at the phylum level in the QFY groups. At the genus level, Akkermansia, Paramuribaculum, Herminiimonas, Erysipelatoclostridium and other genera in the QFY groups showed a significant trend of relative abundance restoration (P<0.01 or P<0.05). CONCLUSION: QFY can improve the memory of MI animals induced by scopolamine hydrobromide by restoring the homeostasis of intestinal microbiota and regulating related indexes in serum and brain tissue.

GHS-R1a deficiency protects against lipopolysaccharide-induced spatial memory impairment in mice.

Neuroinflammation has been implicated in cognitive deficits of neurological and neurodegenerative diseases. There is abundant evidence that the application of ghrelin, an orexigenic hormone regulating appetite and energy balance, abrogates neuroinflammation and rescues associated memory impairment. However, the underlying mechanism is uncertain. In this study, we find that both intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administration of lipopolysaccharide (LPS) impairs spatial memory in mice. LPS treatment causes neuroinflammation and microglial activation in the hippocampus. Ghsr1a deletion suppresses LPS-induced microglial activation and neuroinflammation, and rescued LPS-induced memory impairment. Our findings thus suggest that GHS-R1a signaling may promote microglial immunoactivation and contribute to LPS-induced neuroinflammation. GHS-R1a may be a new therapeutic target for cognitive dysfunction associated with inflammatory conditions.

Liraglutide alleviated alpha-pyrrolidinovalerophenone (α-PVP) induced cognitive deficits in rats by modifying brain mitochondrial impairment.

The use of NPS compounds is increasing, and impairment in spatial learning and memory is a growing concern. Alpha-pyrrolidinovalerophenone (α-PVP) consumption, as a commonly used NPS, can impair spatial learning and memory via the brain mitochondrial dysfunction mechanism. Liraglutide isone of the most well-known Glucagon-Like Peptide 1 (GLP-1) agonists that is used as an anti-diabetic and anti-obesity drug. According to current research, Liraglutide likely ameliorates cognitive impairment in neurodegenerative conditions and substance use disorders. Hence, the purpose of this study is examining the effect of Liraglutide on α-PVP-induced spatial learning and memory problems due to brain mitochondrial dysfunction. Wistar rats (8 in each group) received α-PVP (20 mg/kg/d for 10 consecutive days, intraperitoneally (I.P.)). Then, Liraglutide was administered at 47 and 94 µg/kg/d, I.P., for 4 weeks following the α-PVP administration. The Morris Water Maze (MWM) task evaluated spatial learning and memory 24 h after Liraglutide treatment. Bedside, brain mitochondrial activity parameters, including reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP), cytochrome c release, mitochondrial outer membrane damage and swelling, and brain ADP/ATP ratio, were studied. Our results showed that Liraglutide ameliorated α-PVP-induced spatial learning and memory impairments through alleviating brain mitochondrial dysfunction (which is indicated by increasing ROS formation, collapsed MMP, mitochondrial outer membrane damage, cytochrome c release, mitochondrial swelling, and increased brain ADP/ATP ratio). This study could be used as a starting point for future studies about the possible role of Liraglutide in ameliorating mitochondrial dysfunction leading to substance use disorder- induced cognitive impairment.

Acute 2-phenyl-3-(phenylselanyl)benzofuran treatment reverses the neurobehavioral alterations induced by sleep deprivation in mice.

Sleep is a fundamental state for maintaining the organism homeostasis. Disruptions in sleep patterns predispose to the appearance of memory impairments and mental disorders, including depression. Recent pre-clinical studies have highlighted the antidepressant-like properties of the synthetic compound 2-phenyl-3-(phenylselanyl)benzofuran (SeBZF1). To further investigate the neuromodulatory effects of SeBZF1, this study aimed to assess its therapeutic efficacy in ameliorating neurobehavioral impairments induced by sleep deprivation (SD) in mice. For this purpose, a method known as multiple platforms over water was used to induce rapid eye movement (REM) SD. Two hours after acute SD (24 h), male Swiss mice received a single treatment of SeBZF1 (5 mg/kg, intragastric route) or fluoxetine (a positive control, 20 mg/kg, intraperitoneal route). Subsequently, behavioral tests were conducted to assess spontaneous motor function (open-field test), depressive-like behavior (tail suspension test), and memory deficits (Y-maze test). Brain structures were utilized to evaluate oxidative stress markers, monoamine oxidase (MAO) and acetylcholinesterase (AChE) activities. Our findings revealed that SD animals displayed depressive-like behavior and memory impairments, which were reverted by SeBZF1 and fluoxetine treatments. SeBZF1 also reverted the increase in lipoperoxidation levels and glutathione peroxidase activity in the pre-frontal cortex in mice exposed to SD. Besides, the increase in hippocampal AChE activity induced by SD was overturned by SeBZF1. Lastly, cortical MAO-B activity was reestablished by SeBZF1 in mice that underwent SD. Based on the main findings of this study, it can be inferred that the compound SeBZF1 reverses the neurobehavioral alterations induced by sleep deprivation in male Swiss mice.

[Memory impairments in temporal lobe epilepsy].

Temporal lobe epilepsy is known to present with various cognitive impairments, among which memory deficits are frequently reported by patients. Memory deficits can be classified into two types: classical hippocampal amnesia, which is characterized by abnormalities detected in neuropsychological assessments, and atypical memory deficits, such as accelerated long-term amnesia and autobiographical memory impairment, which cannot be identified using standard testing methods. These deficits are believed to arise from a complex interplay among structural brain abnormalities, interictal epileptic discharges, pharmacological factors, and psychological states. While fundamental treatments are limited, there are opportunities for interventions such as environmental adjustments and rehabilitation. This review article aims to provide a comprehensive overview of the types, underlying pathophysiology, and intervention methods for memory disorders observed in patients with temporal lobe epilepsy.

Methylmercury exposure at dosage conditions that do not affect growth can impair memory in adolescent mice.

Methylmercury is an environmental pollutant that can induce serious central nervous system damage. Its ubiquitous presence in the environment in trace amounts has raised concerns about potential adverse effects on human health. Although many studies have evaluated the effects of methylmercury on neural development in fetal and neonatal mice, there has been less focus on studies using adolescent mice. Therefore, in this study, the effects of methylmercury on brain neurodevelopment and maturation were evaluated by various neurobehavioral trials using adolescent mice exposed to 30 ppm methylmercuric chloride (approximately 24 ppm methylmercury) for up to 8 weeks. Under these administration conditions, weight gain in adolescent mice was unaffected by methylmercury exposure. Furthermore, methylmercury exposure in adolescent mice had no effect on sociability as assessed by the social interaction test, impulsivity as assessed by the cliff avoidance reaction test, depressive behavior as assessed by the tail-suspension test, or locomotor activity as assessed using the Supermex system. In contrast, short-term memory assessed by the Y-maze test, as well as long-term memory assessed by novel object recognition and passive avoidance tests, revealed impairments induced by methylmercury exposure in adolescent mice. These results suggest that long-term exposure to methylmercury during adolescence potentially impairs memory function, and the nervous pathway of brain areas involved in learning and memory are particularly vulnerable to the adverse effects of methylmercury. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-024-00239-y.

Ethanol's impact on the brain: a neurobiological perspective on the mechanisms of memory impairment.

Alcohol consumption is known to have detrimental effects on memory function, with various studies implicating ethanol in the impairment of cognitive processes related to memory retention and retrieval. This review aims to elucidate the complex neurobiological mechanisms underlying ethanol-induced memory impairment. Through a thorough search of existing literature using electronic databases, relevant articles focusing on the neurobiological mechanisms of ethanol on memory were identified and critically evaluated. This review focuses on the molecular and neural pathways through which ethanol exerts its effects on memory formation, consolidation, and recall processes. Key findings from the included studies shed light on the impact of ethanol on neurotransmitter systems, synaptic plasticity, and neuroinflammation in relation to memory impairment. This review contributes to a better understanding of the intricate mechanisms by which alcohol impairs memory function, offering insights for future research directions and the development of targeted interventions to alleviate these cognitive impairments.

Regional hippocampal atrophy reflects memory impairment in patients with early relapsing remitting multiple sclerosis.

BACKGROUND: Research work has shown that hippocampal subfields are atrophic to varying extents in multiple sclerosis (MS) patients. However, studies examining the functional implications of subfield-specific hippocampal damage in early MS are limited. We aim to gain insights into the relationship between hippocampal atrophy and memory function by investigating the correlation between global and regional hippocampal atrophy and memory performance in early MS patients. METHODS: From the Italian Neuroimaging Network Initiative (INNI) dataset, we selected 3D-T1-weighted brain MRIs of 219 early relapsing remitting (RR)MS and 246 healthy controls (HC) to identify hippocampal atrophic areas. At the time of MRI, patients underwent Selective-Reminding-Test (SRT) and Spatial-Recall-Test (SPART) and were classified as mildly (MMI-MS: n.110) or severely (SMI-MS: n:109) memory impaired, according to recently proposed cognitive phenotypes. RESULTS: Early RRMS showed lower hippocampal volumes compared to HC (p < 0.001), while these did not differ between MMI-MS and SMI-MS. In MMI-MS, lower hippocampal volumes correlated with worse memory tests (r = 0.23-0.37, p ≤ 0.01). Atrophic voxels were diffuse in the hippocampus but more prevalent in cornu ammonis (CA, 79%) than in tail (21%). In MMI-MS, decreased subfield volumes correlated with decreases in memory, particularly in the right CA1 (SRT-recall: r = 0.38; SPART: r = 0.34, p < 0.01). No correlations were found in the SMI-MS group. CONCLUSION: Hippocampal atrophy spreads from CA to tail from early disease stages. Subfield hippocampal atrophy is associated with memory impairment in MMI-MS, while this correlation is lost in SMI-MS. This plays in favor of a limited capacity for an adaptive functional reorganization of the hippocampi in MS patients.

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.