Long-term Memory Loss Research Articles

Comparing machine learning and deep learning models to predict cognition progression in Parkinson's disease.

Cognitive decline in Parkinson's disease (PD) varies widely. While models to predict cognitive progression exist, comparing traditional probabilistic models to deep learning methods remains understudied. This study compares sequential modeling techniques to identify cognitive progression in individuals with and without PD. Using data from the Parkinson's Progression Marker Initiative, shallow Markov, deep recurrent (long short-term memory [LSTM]), and nonrecurrent (temporal fusion transformer [TFT]) models were compared to predict cognitive status over time. Cognitive status was categorized into normal cognition (NC), mild cognitive impairment (MCI), and dementia. Predictions were made annually for up to 3 years using clinical data, including demographics, cognitive assessments, PD severity, and medical history. Each approach was evaluated using inverse probability weighted (IPW-) F1 scores. An ensemble method combined outputs from the Markov, LSTM, and TFT models. The dataset included 917 individuals (53% PD; 30% at risk for PD; 17% Healthy Controls). The TFT model outperformed others across all annual periods (IPW-F1 = 0.468) compared to the Markov (IPW-F1 = 0.349) and LSTM (IPW-F1 = 0.414) models, with improved performance using an ensemble approach (IPW-F1 = 0.502). For MCI and dementia predictions, which were rarer occurrences compared to NC status (ratios: 50:8:1), the TFT model consistently outperformed competing models, achieving IPW-F1 scores of 0.496 and 0.533 for MCI and dementia, respectively. In conclusion, sequential deep learning models like TFT, which mitigate long-term memory loss and can interpret complex, high-dimensional data, perform best overall in predicting clinically important cognitive transitions. These methods should be further explored for predicting degenerative conditions.

Variational Analysis of a Dynamic Contact Problem with Wear and Damage Involving Viscoelastic Materials with Long-Term Memory

We investigate a mathematical problem involving dynamic interaction between a viscoelastic body with long-term memory loss and an obstruction. The contact is frictional and bilateral, with a moving rigid base, resulting in wear of the contacting surface. The problem is expressed as a coupled system, with a hyperbolic quasi-variational inequality for displacement and a parabolic variational inequality for damage. We define a variational formulation for the model and demonstrate the existence of a single weak solution to the problem. The material behaviour is explained using a viscoelastic constitutive law that includes long-term memory and damage. Elastic deformations induce material deterioration, which is depicted by a parabolic inclusion. The proof is based on classical existence.

Oral Administration of Bifidobacterium lactis Ameliorates Cognitive Deficits in Mice Intracerebroventricularly Administered Amyloid Beta via Regulation the Activation of Mitogen-activated Protein Kinases.

Probiotics are functional microorganisms that exhibit various biological activities, such as allergic reactions, inflammation, and aging. The aim of this study is to evaluate the effects of Bifidobacterium lactis CBT BL3 (BL) on the amyloid beta (Aβ)-mediated cognitive impairments. Oral administration of live BL to intracerebroventricularly Aβ-injected mice significantly attenuated short- and long-term memory loss estimated using the Y-maze and Morris water maze tests. We found that expression of apoptosis-related proteins such as caspase-9, caspase-3, and cleaved poly (ADP-ribose) polymerase was significantly elevated in the brain tissues of Aβ-injected mouse brains when compared to that of the control mouse group. Interestingly, these expression levels were significantly decreased in the brain tissue of mice fed BL for 6 wk. In addition, the abnormal over-phosphorylation of mitogen-activated protein kinases (MAPKs) such as ERK1/2, p38 MAPK, and JNK in the brain tissue of intracerebroventricularly Aβ-injected mice was significantly attenuated by oral administration of BL. Taken together, the results indicate that Aβ-induced cognitive impairment may be ameliorated by the oral administration of BL by controlling the activation of MAPKs/apoptosis in the brain. This study strongly suggests that BL can be developed as a functional probiotic to attenuate Aβ-mediated cognitive deficits.

Brain Fog: a Narrative Review of the Most Common Mysterious Cognitive Disorder in COVID-19.

It has been more than three years since COVID-19 impacted the lives of millions of people, many of whom suffer from long-term effects known as long-haulers. Notwithstanding multiorgan complaints in long-haulers, signs and symptoms associated with cognitive characteristics commonly known as "brain fog" occur in COVID patients over 50, women, obesity, and asthma at excessive. Brain fog is a set of symptoms that include cognitive impairment, inability to concentrate and multitask, and short-term and long-term memory loss. Of course, brain fog contributes to high levels of anxiety and stress, necessitating an empathetic response to this group of COVID patients. Although the etiology of brain fog in COVID-19 is currently unknown, regarding the mechanisms of pathogenesis, the following hypotheses exist: activation of astrocytes and microglia to release pro-inflammatory cytokines, aggregation of tau protein, and COVID-19 entry in the brain can trigger an autoimmune reaction. There are currently no specific tests to detect brain fog or any specific cognitive rehabilitation methods. However, a healthy lifestyle can help reduce symptoms to some extent, and symptom-based clinical management is also well suited to minimize brain fog side effects in COVID-19 patients. Therefore, this review discusses mechanisms of SARS-CoV-2 pathogenesis that may contribute to brain fog, as well as some approaches to providing therapies that may help COVID-19 patients avoid annoying brain fog symptoms.

TAC1 Gene Therapy in the Gut to Reduce Long-Term Memory Loss in Tg4-42 Alzheimer Diseased Mice: A Research Proposal

Alzheimer’s disease (AD) is a neurodegenerative disorder that mainly affects a large percentage of the older adult population. AD can cause many problems, most notably long-term memory (LTM) loss. Many studies have observed a decreased level of substance P (SP) in the hippocampus of individuals with AD. In this paper, we propose a novel strategy to limit AD-related decline of LTM using probiotics transformed with SP. These transformed bacteria will contain varying concentrations of SP and will be injected into three different segments of the proximal colon in AD mouse models. LTM will be measured through Morris Water Maze (MWM) and Barnes Maze (BM) tests over three months to examine improvements in spatial memory. It is anticipated that this experiment will demonstrate that increased concentrations of SP in the proximal colon will result in the greatest reduction in LTM loss in AD individuals. This experiment will establish a new therapeutic option for AD individuals to slow the progression of LTM loss.

Correlation of HIV-Induced Neuroinflammation and Synaptopathy with Impairment of Learning and Memory in Mice with HAND.

Over 38 million people worldwide are living with HIV/AIDS, and more than half of them are affected by HIV-associated neurocognitive disorders (HAND). Such disorders are characterized by chronic neuroinflammation, neurotoxicity, and central nervous system deterioration, which lead to short- or long-term memory loss, cognitive impairment, and motor skill deficits that may show gender disparities. However, the underlying mechanisms remain unclear. Our previous study suggested that HIV-1 infection and viral protein R (Vpr) upregulate the SUR1-TRPM4 channel associated with neuroinflammation, which may contribute to HAND. The present study aimed to explore this relationship in a mouse model of HAND. This study employed the HIV transgenic Tg26 mouse model, comparing Tg26 mice with wildtype mice in various cognitive behavioral and memory tests, including locomotor activity tests, recognition memory tests, and spatial learning and memory tests. The study found that Tg26 mice exhibited impaired cognitive skills and reduced learning abilities compared to wildtype mice, particularly in spatial memory. Interestingly, male Tg26 mice displayed significant differences in spatial memory losses (p < 0.001), while no significant differences were identified in female mice. Consistent with our early results, SUR1-TRPM4 channels were upregulated in Tg26 mice along with glial fibrillary acidic protein (GFAP) and aquaporin 4 (AQP4), consistent with reactive astrocytosis and neuroinflammation. Corresponding reductions in neurosynaptic responses, as indicated by downregulation of Synapsin-1 (SYN1) and Synaptophysin (SYP), suggested synaptopathy as a possible mechanism underlying cognitive and motor skill deficits. In conclusion, our study suggests a possible relationship between SUR1-TRPM4-mediated neuroinflammation and synaptopathy with impairments of learning and memory in mice with HAND. These findings could help to develop new therapeutic strategies for individuals living with HAND.

The Role of Estrogen Therapy as a Protective Factor for Alzheimer's Disease and Dementia in Postmenopausal Women: A Comprehensive Review of the Literature.

The complete cessation of menstruation for 12 months with associated vasomotor symptoms is termed menopause.Apart from playing a role in reproduction, estrogen significantly affects the central nervous system (CNS). Population-based studies highlighted a substantial difference in the prevalence of dementia between men and women, with Alzheimer-associated dementia being more prevalent in women, indicating that estrogen deficiency might be a risk factor for neurodegenerative diseases. Patients with dementia experience a progressive decline in neurocognitive function, beginning with short-term memory loss that progresses to long-term memory loss and the inability to perform everyday activities, leading ultimately to death.There is currently no cure for dementia, so preventing or slowing the disease's progression is paramount. Accordingly, researchers have widely studied the role of estrogen as a neuroprotective agent. Estrogen prevents dementia by augmenting Hippocampal and prefrontal cortex function, reducing neuroinflammation, preventing degradation of estrogen receptors, decreasing oxidative damage to the brain, and increasing cholinergic and serotonergic function. According to the window phase hypothesis, estrogen's effect on preventing dementia is more pronounced if therapy is started early, during the first five years of menopause.Other studies like The Woman's Health Initiative Memory Study (WHIMS) showed unfavorable effects of estrogen on the brain. This review aims to establish an understanding of the currently available data on estrogen's effect on neurodegeneration, namely, dementia and Alzheimer's disease.

The microRNA-485-3p concentration in salivary exosome-enriched extracellular vesicles is related to amyloid β deposition in the brain of patients with Alzheimer’s disease

ObjectivesAlzheimer’s disease (AD) is an irreversible neurodegenerative disease characterized by progressive long-term memory loss and cognitive dysfunction. Neuroimaging tests for abnormal amyloid-β (Aβ) deposition are considered the most reliable methods for the diagnosis of AD; however, the cost for such testing is very high and generally not covered by national insurance systems. Accordingly, it is only recommended for individuals exhibiting clinical symptoms of AD supported by clinical cognitive assessments. Recently, it was suggested that dysregulated microRNA-485-3p (miRNA-485-3p) in the brain and cerebrospinal fluid is closely related to pathogenesis of AD. However, a relationship between circulating miRNA-485-3p in salivary exosome-enriched extracellular vesicles (EE-EV) and Aβ deposition in the brain has not been observed. Design & methodsUsing quantitative real-time polymerase chain reaction, we analyzed miRNA-485-3p concentration in salivary EE-EV. We used receiver operating characteristic (ROC) curve analysis to evaluate its predictive value for Aβ positron emission tomography (Aβ-PET) positivity in patients with AD. ResultsOur results showed that the miRNA-485-3p concentration in salivary EE-EV isolated from patients with AD was significantly increased compared with that in the healthy controls (p < 0.0001). In the analysis of all participants, the miRNA-485-3p concentration was significantly increased in Aβ-PET-positive participants compared to Aβ-PET-negative participants (p < 0.0001). Further analysis using only AD patients also showed that the miRNA-485-3p concentration was significantly increased in Aβ-PET-positive AD patients vs. Aβ-PET-negative AD patients (p = 0.0063). The ROC curve analysis for differentiating Aβ-PET-positive and negative participants showed that the area under the curve for miRNA-485-3p was 0.9217. ConclusionThese findings suggested that the miRNA-485-3p concentration in salivary EE-EV was closely related to Aβ deposition in the brain and had high diagnostic accuracy for predicting Aβ-PET positivity.

Neuroprotective effects of PRG on Aβ25-35-induced cytotoxicity through activation of the ERK1/2 signaling pathway

Ethnopharmacological relevancePhylloporia ribis (Schumach:Fr.)Ryvarden is a genus of needle Phellinus medicinal fungi, parasitic on the living rhizomes of hawthorn and pear trees. As a traditional Chinese medicine, Phylloporia ribis was used in folklore for long-term illness, weakness and memory loss in old age. Previous studies have shown that polysaccharides from Phylloporia ribis (PRG) significantly promoted synaptic growth in PC12 cells in a dose-dependent manner, exhibiting “NGF”-like neurotrophic activity. Aβ25-35 damage to PC12 cells produced neurotoxicity and decreased cell survival, and PRG reduced the apoptosis rate, suggesting that PRG has neuroprotective effects. The studies confirmed that PRG had the potential to be a neuroprotective agent, but its neuroprotective mechanism remained unclear. Aim of the studyWe aimed to elucidate the neuroprotective effects of PRG in an Aβ25-35-induced Alzheimer's disease (AD) model. Materials and methodsHighly-differentiated PC12 cells were treated with Aβ25-35 (AD model) and PRG, and were assessed for cellular apoptosis, inflammatory factors, oxidative stress, and kinase phosphorylation. ResultsThe results showed that the PRG groups effectively inhibited the neurotoxicity, mainly manifested by inhibiting mitochondrial oxidative stress, attenuating neuroinflammatory responses, and improving mitochondrial energy metabolism, eventually resulting in higher cell survival. The expression of p-ERK, p-CREB and BDNF proteins was increased in the PRG groups compared to the model group, which confirmed that PRG reversed the inhibition of the ERK pathway. ConclusionWe provide evidence for neuroprotection conferred by PRG and its mechanism by inhibiting ERK1/2 hyper-phosphorylation, prevention of mitochondrial stress, and subsequent prevention of apoptosis. The study highlights PRG as a promising candidate with neuroprotective effects, the potential of which can be harnessed for identifying novel therapeutic targets.

Exploring the therapeutic efficacy of Chlorella pyrenoidosa peptides in ameliorating Alzheimer's disease

Alzheimer's disease (AD) is one of the neurodegenerative disorders, the hallmarks of which include deposits of extracellular beta-amyloid (Aβ) as well as intracellular tau neurofibrillary tangles (NFTs) tangles. With disease progression, neuronal apoptosis combined with cerebral atrophy occurs, leading to cognitive impairment and long-term memory loss. Recently, Chlorella species have been identified as a functional food and are being explored for the prevention of various diseases widely studied to prevent or treat many neurodegenerative diseases. Hence, we for the first time investigated the neuroprotective effects of Chlorella pyrenoidosa short-chain peptides (CPPs) i.e. <1 kDa, 1–3 kDa, 3–10 kDa, and >10 kDa on the in vitro and in vivo neuronal injury models. Our in vitro results showed that CPP with a molecular weight of 1–3 kDa and 3–10 kDa could elevate the survival rate of Aβ1-42 or l-Glutamic acid-injured N2A cells. These treatments also inhibited Aβ and tau NFTs in N2A cells and prevented progressive neuronal cellular damage by suppressing inflammatory cytokines such as PGE2, iNOS, IL-6, TNF-α, COX-2, IL-1β, TGF-β1, and NF-κB. Further, our in vivo Aβ1-42-induced AD mice model demonstrated that 1–3 kDa or 3–10 kDa CPP could improve spatial cognition and learning memory. We also observed a decreased cell loss ratio in CA1-CA3 hippocampal regions. Taken together, our findings imply that CPPs may exert their anti-AD impact through anti-inflammatory, and anti-amyloid activities via reducing APP and tau NFT.

Long-Term Memory Formation in Drosophila Depends on the 3'UTR of CPEB Gene orb2.

Activation of local translation in neurites in response to stimulation is an important step in the formation of long-term memory (LTM). CPEB proteins are a family of translation factors involved in LTM formation. The Drosophila CPEB protein Orb2 plays an important role in the development and function of the nervous system. Mutations of the coding region of the orb2 gene have previously been shown to impair LTM formation. We found that a deletion of the 3'UTR of the orb2 gene similarly results in loss of LTM in Drosophila. As a result of the deletion, the content of the Orb2 protein remained the same in the neuron soma, but significantly decreased in synapses. Using RNA immunoprecipitation followed by high-throughput sequencing, we detected more than 6000 potential Orb2 mRNA targets expressed in the Drosophila brain. Importantly, deletion of the 3'UTR of orb2 mRNA also affected the localization of the Csp, Pyd, and Eya proteins, which are encoded by putative mRNA targets of Orb2. Therefore, the 3'UTR of the orb2 mRNA is important for the proper localization of Orb2 and other proteins in synapses of neurons and the brain as a whole, providing a molecular basis for LTM formation.

Влияние фактора интерференции социальных сетей на процессы консолидации памяти у подростков

The relevance of this study is due to the need to answer the question of how the factors of digital medium affect the development of mental functions in the younder generation. The study was aimed to assess the effects of the social media interference factor on memory (auditory-speech and visual-figurative) consolidation in adolescents. The sample was 130 adolescents aged 11–17. The groups were formed based on the age stages (11–12, 13–14, 15–17 years). The study involved the use of the method for the diagnosis of the short-term auditory-speech and visual-figurative memory span. Viewing video content and reading the fragment of the fiction book were used as interference. A significant decrease in the short-term auditory-speech and visual-figurative memory span was observed in adolescents. The short-term memory span is reduced in the context of social media interference (prolonged continuous viewing the heterogenous visual-acoustic and visualspeech content). The high risk of the long-term memory loss due to the impact of the social media interference factor on memory consolidation in adolescents is empirically proven. The more the duration of the maximum continuous video stream and the total time the adolescents spend on Internet (including social media), the larger is the loss of information.

Long-lasting brain fog is related with severity clusters of symptoms in COVID-19 patients.

COVID-19 patients may experience Long-lasting symptoms from weeks to even months. To evaluate long-term cognitive impairment based on the severity of symptoms of COVID-19 infection in a primary health system setting. From a database of 363 patients, 83 cases aged 47 ± 15 years, (58% females) were selected from June to August 2020. In patients who survived the virus, 24 infection-related symptoms were collected to create three severity clusters (mild, moderate, and severe). The follow-up time was at least seven months. Comparing the first two clusters with the severe cluster, the existence of brain fog and risk factors (obesity, hypertension, diabetes, chronic lung disease, and hypothyroidism) were analyzed. Thirty-one patients (37%) had persistent symptoms lasting up to 240 days. Fifty-one patients (61%) experienced brain fog. Concentration was affected by symptom severity (odds ratio [OR] 3.63, 95% confidence interval [CI] 1.26-10.46, p = 0.02). Short- or long-term memory loss was not affected. Moreover, symptom severity was related to brain fog (OR 3.16, 95% CI 1.05-9.51, p = 0.04). Patients with persistent symptoms had a concentration impairment associated with severity patterns (OR 24.3, 95% CI 1.73-340.11, p = 0.03). Brain fog is associated with symptom severity in COVID-19 survivors and lasts for more than eight months.

Progress of advanced nanomaterials in diagnosis of neurodegenerative diseases

Neurodegenerative diseases (NDDs) encompass a wide range of clinically and pathologically diverse diseases characterized by progressive long-term cognitive decline, memory and function loss in daily life. Due to the lack of effective drugs and therapeutic strategies for preventing or delaying neurodegenerative progression, it is urgent to diagnose NDDs as early and accurately as possible. Nanomaterials, emerged as one of the most promising materials in the 21st century, have been widely applied and play a significant role in diagnosis and treatment of NDDs because of their remarkable properties including stability, prominent biocompatibility, unique structure, novel physical and chemical characteristics. In this review, we outlined general strategies for the application of different types of advanced materials in early and staged diagnosis of NDDs in vivo and in vitro. According to applied technology, in vivo research mainly involves magnetic resonance, fluorescence, and surface enhanced Raman imaging on structures of brain tissues, cerebral vessels and related distributions of biomarkers. In vitro research is focused on the detection of fluid biomarkers in cerebrospinal fluid and peripheral blood based on fluorescence, electrochemical, Raman and surface plasmon resonance techniques. Finally, we discussed the current challenges and future perspectives of biomarker-based NDDs diagnosis as well as potential applications regarding advanced nanomaterials.

Cornel Iridoid Glycoside Alleviates Microglia-Mediated Inflammatory Response via the NLRP3/Calpain Pathway.

Vascular dementia (VaD) is associated with cerebral hypoperfusion, which results in long-term cognitive impairment and memory loss. Cornel iridoid glycoside (CIG) is the major active constituent isolated from the ripe fruit of Cornus officinalis. Previous studies have shown that CIG enhances neurological function in VaD rats. In the present research, we attempted to clarify the molecular processes underlying the role of CIG in neuroinflammation in VaD. We created a chronic cerebral ischemia rat model by ligation of the bilateral common carotid arteries (2VO) and then treated rats with different concentrations of CIG. Comprehensive analyses revealed that CIG ameliorated myelin integrity and neuronal loss. Furthermore, we also found that CIG inhibited polarized microglia activation and attenuated inflammasome-mediated production of proinflammatory cytokines in BV2 microglia cells induced by LPS/IFN-γ and in the brains of 2VO rats. To further elucidate the role of CIG in microglia-mediated inflammatory response, we investigated the expression and activity of calpain. CIG inhibited the expression and activity of calpain 1/2, which was characterized by decreased calpastatin and spectrin αII expression. In particular, intra- and extracellular calpain 1 levels were reduced by CIG. However, CIG showed weak interaction with calpain 1. In addition, we found that CG administration significantly repressed the assembly of the NOD-like receptor protein 3 (NLRP3) inflammasome, including NLRP3, ASC, and caspase-1. In conclusion, our knowledge of the mechanisms by which CIG regulates NLRP3/calpain signaling to influence inflammatory responses offers further insights into potential therapeutic strategies to treat VaD.

Brain, Memory, and Amnesia

Amnesia is a large-scale and long-term memory loss. Complications of amnesia, including the inability to create new memories and learn new things, severely reduce the quality of an individual's life. In the last three centuries, many famous clinical studies, including the one involving Henry Molaison (H.M), have been completed, furthering our understanding of the brain’s memory system and amnesia. Especially, a variety of psychological and neurological causes of amnesia have been identified. Different treatments are available for different types of amnesia; however, due to the extensive causes of amnesia, finding a common cure has proven to be difficult. This review will focus on our current understanding of the memory system and history of amnesia as well as the types, causes, preventive measures, and potential treatment strategies of amnesia.

Treatment With an Angiopoietin-1 Mimetic Peptide Improves Cognitive Outcome in Rats With Vascular Dementia.

Background and PurposeVascular dementia (VaD) is a complex neurodegenerative disease affecting cognition and memory. There is a lack of approved pharmacological treatments specifically for VaD. In this study, we investigate the therapeutic effects of AV-001, a Tie2 receptor agonist, in middle-aged rats subjected to a multiple microinfarct (MMI) model of VaD.MethodsMale, 10–12 month-old, Wistar rats were employed. The following experimental groups were used: Sham, MMI, MMI+1 μg/Kg AV-001, MMI+3 μg/Kg AV-001, MMI+6 μg/Kg AV-001. AV-001 treatment was initiated at 1 day after MMI and administered once daily via intraperitoneal injection. An investigator blinded to the experimental groups conducted a battery of neuro-cognitive tests including modified neurological severity score (mNSS) test, novel object recognition test, novel odor recognition test, three chamber social interaction test, and Morris water maze test. Rats were sacrificed at 6 weeks after MMI.ResultsThere was no mortality observed after 1, 3, or 6 μg/Kg AV-001 treatment in middle-aged rats subjected to MMI. AV-001 treatment (1, 3, or 6 μg/Kg) does not significantly alter blood pressure or heart rate at 6 weeks after MMI compared to baseline values or the MMI control group. Treatment of MMI with 1 or 3 μg/Kg AV-001 treatment does not significantly alter body weight compared to Sham or MMI control group. While 6 μg/Kg AV-001 treated group exhibit significantly lower body weight compared to Sham and MMI control group, the weight loss is evident starting at 1 day after MMI when treatment was initiated and is not significantly different compared to its baseline values at day 0 or day 1 after MMI. AV-001 treatment significantly decreases serum alanine aminotransferase, serum creatinine, and serum troponin I levels compared to the MMI control group; however, all values are within normal range. MMI induces mild neurological deficits in middle-aged rats indicated by low mNSS scores (<6 on a scale of 0–18). Compared to control MMI group, 1 μg/Kg AV-001 treatment group did not exhibit significantly different mNSS scores, while 3 and 6 μg/Kg AV-001 treatment induced significantly worse mNSS scores on days 21–42 and 14–42 after MMI, respectively. MMI in middle-aged rats induces significant cognitive impairment including short-term memory loss, long-term memory loss, reduced preference for social novelty and impaired spatial learning and memory compared to sham control rats. Rats treated with 1 μg/Kg AV-001 exhibit significantly improved short-term and long-term memory, increased preference for social novelty, and improved spatial learning and memory compared to MMI rats. Treatment with 3 μg/Kg AV-001 improves short-term memory and preference for social novelty but does not improve long-term memory or spatial learning and memory compared to MMI rats. Treatment with 6 μg/Kg AV-001 improves only long-term memory compared to MMI rats. Thus, 1 μg/Kg AV-001 treatment was selected as an optimal dose. Treatment of middle-aged rats subjected to MMI with 1 μg/Kg AV-001 significantly increases axon density, myelin density and myelin thickness in the corpus callosum, as well as increases synaptic protein expression, neuronal branching and dendritic spine density in the cortex, oligodendrocytes and oligodendrocyte progenitor cell number in the cortex and striatum and promotes neurogenesis in the subventricular zone compared to control MMI rats.ConclusionsIn this study, we present AV-001 as a novel therapeutic agent to improve cognitive function and reduce white matter injury in middle aged-rats subjected to a MMI model of VaD. Treatment of MMI with 1 μg/Kg AV-001 significantly improves cognitive function, and increases axon density, remyelination and neuroplasticity in the brain of middle-aged rats.

1,3‐Butanediol Mitigates High‐Salt Diet Induced Cognitive Impairment in Aging Mice

Vascular dementia (VaD) is the second most common form of dementia after Alzheimer’s disease (AD). Hypertension is the second leading risk factor for developing neurodegenerative disease. A recent study reported that Dietary salt promotes cognitive impairment through tau phosphorylation. However, the effect of ketone bodies or the precursor molecule (1,3‐butanediol) supplementation on cognitive impairment in aged mice or the absence of high salt has not been investigated. The study tests the hypothesis that 1,3‐butanediol attenuates the progression of vascular dementia mediated through histone acetylation mechanism in hypertensive aged mice. To test this hypothesis, we employed old male and female wild‐type (WT) mice. For three months, the mice were fed with a high salt diet (HSD) (8%). HSD mice have supplemented with ketone bodies precursor, 1,3‐Butanediol (2%), and ketone bodies compound β‐hydroxybutyrate (BHB, 0.2%) in drinking water for 12 weeks. Blood pressure was measured after 12 weeks of treatment by tail‐cuff plethysmography. After 12 weeks, urine and tissues were collected. The results show that 1,3‐Butanediol or BHB treatment reduced blood pressure and miRNA‐128‐3p in aged hypertensive mice. Further, the data analysis revealed the loss of short‐term and long‐term memory in HSD‐hypertensive mice compared to HSD+BHB or HSD+ 1,3‐Butanediol mice. This mechanistic study shows that HSD+ 1,3‐Butanediol mice display an increased mitochondrial TFAM dependent upregulation of brain‐derived neurotrophic factor (BDNF) and nuclear receptor subfamily 4A (Nr4a) in the mouse hippocampus via activation of the H3K27ac acetylation at the promoter. In addition, the anti‐miR‐128 treatment restored neuroprotective function and reduced the dementia pathology in old‐hypertensive mice. The present data demonstrate that 1,3‐Butanediol or BHB increases ketone bodies production and improves cognitive functions in aged hypertensive mice and could be a novel nutritional intervention for vascular dementia treatment.

Neuroligin-1 plays an important role in methamphetamine-induced hippocampal synaptic plasticity

The neurotoxic effects of methamphetamine (METH) include not only neuronal apoptosis and autophagy, but also lead to substance use disorder and have become increasingly prominent. Studies suggest that synaptic plasticity may be the structural basis of METH-induced neurological impairment. Neuroligins are postsynaptic adhesion molecules involved in the regulation of synaptic organization and function. Animal studies have shown that neuroligin (NLG)− 1 is involved in memory formation; however, its role in METH-induced neurotoxicity is not clear. In the present study, we used 1 mM METH in vitro; mice in the acute and subacute exposure groups received intraperitoneal injections of 30 mg/kg METH (1 injection) or 15 mg/kg METH (8 separate injections at 12-h intervals). We found that the expression of NLG-1, Synapsin-1, and postsynaptic density-95 were increased after METH exposure. We further observed that METH-induced inhibition of long-term potentiation and spatial memory loss could be alleviated when mice were pretreated with NLG-1 small interfering RNA. Therefore, our study provides evidence that NLG-1 is involved in METH-induced hippocampal synaptic plasticity and may be a potential target for the treatment of METH-induced neurotoxicity.

Deformed wing virus infection affects the neurological function of Apis mellifera by altering extracellular adenosine signaling

Deformed wing virus (DWV) infection is believed to be closely associated with colony losses of honeybee (Apis mellifera) due to reduced learning and memory of infected bees. The adenosine (Ado) pathway is important for maintaining immunity and memory function in animals, and it enhances antivirus responses by regulating carbohydrate metabolism in insects. Nevertheless, its effect on the memory of invertebrates is not yet clear. This study investigated how the Ado pathway regulates energy metabolism and memory in honeybees following DWV infection. Decreased Ado receptor (Ado-R) expression in the brain of infected bees resulted in a carbohydrate imbalance as well as impairments of glutamate-glutamine (Glu-Gln) cycle and long-term memory. Dietary supplementation with Ado not only increased the brain energy metabolism but also rescued long-term memory loss by upregulating the expression of memory-related genes. The present study demonstrated the regulation of the Ado pathway upon DWV infection and provides insights into the mechanisms underlying energy regulation and the neurological function of honeybees.