Learning Memory Research Articles

Electroacupuncture improves cognitive impairment after ischemic stroke based on regulation of mitochondrial dynamics through SIRT1/PGC-1α pathway

In recent years, the mechanism of acupuncture in the treatment of post-stroke cognitive impairment (PSCI) has not been fully elucidated. The balance between mitochondrial fission and fusion is important for PSCI. Our previous research demonstrated that electroacupuncture can improve learning and memory in middle cerebral artery ischemia reperfusion (MCAO/R) rats. However, the specific mechanism by which electroacupuncture improves learning and memory in MCAO/R rats by regulating mitochondrial fission and fusion needs to be further investigated. The MCAO/R rats was developed using the line-bolt method. The rats were randomly divided into sham-operated (Sham), model (MCAO/R), electroacupuncture (MCAO/R + EA) and sham-electroacupuncture (MCAO/R + sham EA) groups. Investigating the effects of EA on the expression of Sirtuin1 (SIRT1), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), Optic atrophy 1R + (OPA1) and Dynamin-related protein 1 (DRP1) in hippocampal neurons and on the morphology and function of hippocampal neurons and mitochondria. EA was able to reduce neurologic deficit scores and cerebral infarct volume and improve new object discrimination in MCAO/R rats, but there were no significant changes in these indices in the sham-electroacupuncture group. Moreover, EA increased the expression of SIRT1, PGC-1α, and OPA1 in hippocampal tissues, inhibited the expression of DRP1, attenuated neuronal and mitochondrial damage, and reduced mitochondrial fragmentation. The mechanism by which EA improves learning memory deficits in MCAO/R rats may be related to the inhibition of SIRT1/PGC-1α expression, the enhancement of mitochondrial fusion and the obstruction of its fission, and the reduction of hippocampal neuronal damage.

LAM Test: A New Cognitive Marker for Early Detection in Preclinical Alzheimer's Disease.

With the arrival of disease-modifying treatments, it is mandatory to find new cognitive markers that are sensitive to Alzheimer's disease (AD) pathology in preclinical stages. To determine the utility of a newly developed Learning and Associative Memory face test: LAM test. This study examined the relationship between AD cerebrospinal fluid (CSF) biomarkers and performance on LAM test, and assessed its potential clinical applicability to detect subtle changes in cognitively healthy subjects at risk for AD. We studied eighty cognitively healthy volunteers from the Valdecilla cohort. 61% were women and the mean age was 67.34 years (±6.416). All participants underwent a lumbar puncture for determination of CSF biomarkers and an extensive neuropsychological assessment, including performance on learning and associative memory indices of the LAM-test after 30 min and after 1 week, and two classic word lists to assess verbal episodic memory: the Rey Auditory Verbal Learning Test (RAVLT) and the Free and Cued Selective Reminding Test (FCSRT). We analyzed cognitive performance according to amyloid status (A+ versus A-) and to ATN model (A-T-N-; A+T-N-; A+T+N-/A+T+N+). Performance on the LAM-test was significantly correlated with CSF Aβ ratio. A+ participants performed worse on both learning (mean difference = 2.19, p = 0.002) and memory LAM measures than A- (mean difference = 2.19, p = 0.004). A decline in performance was observed along the Alzheimer's continuum, with significant differences between ATN groups. Our findings suggest that LAM test could be a useful tool for the early detection of subjects within the AD continuum, outperforming classical memory tests.

The Importance of Playing from Memory: Considering the Multi-Sensory Approach in Memorizing Music

It is important for students to play from memory in musical learning. However, some students are afraid of memory lapses. This paper will focus on the benefits of performing from memory in terms of performers and audiences and then introduce the advantages and disadvantages of three types of sensory memory: kinesthetic memory, visual memory and aural memory. Finally, this essay will emphasize the importance of a multi-sensory approach to memorizing music. After that, some methods can be considered by instrumental teachers to help students memorize music.

Differential efficacy of modified enriched environment on motor, emotion, and cognition in cortical ischemic mice.

A modified enriched environment (mEE) with 12 h per night was recently proposed and exhibited cognitive improvement. The present study aimed to evaluate the effects of different courses of mEE on different deficits in ischemic mice. Mice were subjected to photothrombotic stroke at the left sensorimotor cortex and then randomly assigned to standard environment or mEE for 7 d (St-PE) or 28d (Ct-PE) on the third day post-stroke. Neurological deficits and sensorimotor, emotional, and cognitive performances were assessed at the 10th, 17th, and 31st days post-stroke. Our results demonstrated that Ct-PE ameliorated neurological deficits, forelimb using asymmetry, and reduced slip rates of the affected limbs at all time points, while this effect of St-PE was observed only on the 10th day. Similarly, Ct-PE for 28d promoted spatial learning and working memory, but St-PE did not. Differently, ischemic mice in both St-PE and Ct-PE groups exhibited increased exploration behavior in the open field, light-dark box and elevated plus maze, and less immobile behavior during the tail suspension at all the time points. Our findings indicated that Ct-PE improved sensorimotor and cognitive dysfunctions after cortical ischemia in a time-dependent manner, but St-PE appeared to have greater therapeutic potential on anxiety and depression.

Presynaptic Rac1 in the hippocampus selectively regulates working memory

One of the most extensively studied members of the Ras superfamily of small GTPases, Rac1 is an intracellular signal transducer that remodels actin and phosphorylation signaling networks. Previous studies have shown that Rac1-mediated signaling is associated with hippocampal-dependent working memory and longer-term forms of learning and memory and that Rac1 can modulate forms of both pre- and postsynaptic plasticity. How these different cognitive functions and forms of plasticity mediated by Rac1 are linked, however, is unclear. Here, we show that spatial working memory in mice is selectively impaired following the expression of a genetically encoded Rac1 inhibitor at presynaptic terminals, while longer-term cognitive processes are affected by Rac1 inhibition at postsynaptic sites. To investigate the regulatory mechanisms of this presynaptic process, we leveraged new advances in mass spectrometry to identify the proteomic and post-translational landscape of presynaptic Rac1 signaling. We identified serine/threonine kinases and phosphorylated cytoskeletal signaling and synaptic vesicle proteins enriched with active Rac1. The phosphorylated sites in these proteins are at positions likely to have regulatory effects on synaptic vesicles. Consistent with this, we also report changes in the distribution and morphology of synaptic vesicles and in postsynaptic ultrastructure following presynaptic Rac1 inhibition. Overall, this study reveals a previously unrecognized presynaptic role of Rac1 signaling in cognitive processes and provides insights into its potential regulatory mechanisms.

Presynaptic Rac1 in the hippocampus selectively regulates working memory.

One of the most extensively studied members of the Ras superfamily of small GTPases, Rac1 is an intracellular signal transducer that remodels actin and phosphorylation signaling networks. Previous studies have shown that Rac1-mediated signaling is associated with hippocampal-dependent working memory and longer-term forms of learning and memory and that Rac1 can modulate forms of both pre- and postsynaptic plasticity. How these different cognitive functions and forms of plasticity mediated by Rac1 are linked, however, is unclear. Here, we show that spatial working memory in mice is selectively impaired following the expression of a genetically encoded Rac1 inhibitor at presynaptic terminals, while longer-term cognitive processes are affected by Rac1 inhibition at postsynaptic sites. To investigate the regulatory mechanisms of this presynaptic process, we leveraged new advances in mass spectrometry to identify the proteomic and post-translational landscape of presynaptic Rac1 signaling. We identified serine/threonine kinases and phosphorylated cytoskeletal signaling and synaptic vesicle proteins enriched with active Rac1. The phosphorylated sites in these proteins are at positions likely to have regulatory effects on synaptic vesicles. Consistent with this, we also report changes in the distribution and morphology of synaptic vesicles and in postsynaptic ultrastructure following presynaptic Rac1 inhibition. Overall, this study reveals a previously unrecognized presynaptic role of Rac1 signaling in cognitive processes and provides insights into its potential regulatory mechanisms.

Waddington landscape for prototype learning in generalized Hopfield networks

Networks in machine learning offer examples of complex high-dimensional dynamical systems inspired by and reminiscent of biological systems. Here, we study the learning dynamics of generalized Hopfield networks, which permit visualization of internal memories. These networks have been shown to proceed through a “feature-to-prototype” transition, as the strength of network nonlinearity is increased, wherein the learned, or terminal, states of internal memories transition from mixed to pure states. Focusing on the prototype learning dynamics of the internal memories, we observe stereotypical dynamics of memories wherein similar subgroups of memories sequentially split at well-defined saddles. The splitting order is interpretable and reproducible from one simulation to the other. The dynamics prior to splits are robust to variations in many features of the system. To develop a more rigorous understanding of these global dynamics, we study smaller subsystems that exhibit similar properties to the full system. Within these smaller systems, we combine analytical calculations with numerical simulations to study the dynamics of the feature-to-prototype transition, and the emergence of saddle points in the learning landscape. We exhibit regimes where saddles appear and disappear through saddle-node bifurcations, qualitatively changing the distribution of learned memories as the strength of the nonlinearity is varied—allowing us to systematically investigate the mechanisms that underlie the emergence of the learning dynamics. Several features of the learning dynamics are reminiscent of the Waddington's caricature of cellular differentiation, and we attempt to make this analogy more precise. Memories can thus differentiate in a predictive and controlled way, revealing bridges between experimental biology, dynamical systems theory, and machine learning. Published by the American Physical Society 2024

Selective consolidation of learning and memory via recall-gated plasticity.

In a variety of species and behavioral contexts, learning and memory formation recruits two neural systems, with initial plasticity in one system being consolidated into the other over time. Moreover, consolidation is known to be selective; that is, some experiences are more likely to be consolidated into long-term memory than others. Here, we propose and analyze a model that captures common computational principles underlying such phenomena. The key component of this model is a mechanism by which a long-term learning and memory system prioritizes the storage of synaptic changes that are consistent with prior updates to the short-term system. This mechanism, which we refer to as recall-gated consolidation, has the effect of shielding long-term memory from spurious synaptic changes, enabling it to focus on reliable signals in the environment. We describe neural circuit implementations of this model for different types of learning problems, including supervised learning, reinforcement learning, and autoassociative memory storage. These implementations involve synaptic plasticity rules modulated by factors such as prediction accuracy, decision confidence, or familiarity. We then develop an analytical theory of the learning and memory performance of the model, in comparison to alternatives relying only on synapse-local consolidation mechanisms. We find that recall-gated consolidation provides significant advantages, substantially amplifying the signal-to-noise ratio with which memories can be stored in noisy environments. We show that recall-gated consolidation gives rise to a number of phenomena that are present in behavioral learning paradigms, including spaced learning effects, task-dependent rates of consolidation, and differing neural representations in short- and long-term pathways.

Sleep apnea in schizophrenia: Estimating prevalence and impact on cognition

Undertreated medical illnesses can compound the disabling cognitive deficits of schizophrenia. Obstructive sleep apnea (OSA) impairs cognitive domains also affected by schizophrenia, is common, and is treatable. The effects of sleep apnea on cognition in schizophrenia, however, are not well understood. We estimated the prevalence of OSA in a previously characterized sample of 3942 Veterans with schizophrenia by self-report and with a predictive model to identify individuals at high risk for OSA. We then compared neuropsychological and functional capacity assessment results between those who reported OSA versus those who did not, and between those predicted to have OSA versus predicted to not have OSA. We expected that many Veterans not reporting sleep apnea would be predicted to have it, and that both reported and predicted sleep apnea would be associated with lower cognitive and functional performance. The reported prevalence of OSA in the sample was 14%, whereas 72% were predicted to be at high risk of OSA. Interestingly, participants who reported having OSA had better cognitive and functional capacity performance (p's < 0.001) compared to those who did not report OSA, particularly on speed of processing assessments (p < 0.001). Predicted OSA, by contrast, was associated with lower speed of processing, verbal learning and working memory test scores (p's < 0.001). One possible interpretation of these results is that people with higher cognitive capacity may be more likely to seek medical care, while those with cognitive impairments are at greater risk for having untreated co-occurring medical conditions that further compromise cognition.

Therapeutic potential of Aloe vera-coated curcumin encapsulated nanoparticles in an Alzheimer-induced mice model: behavioural, biochemical and histopathological evidence

Objective The main purpose of the present study was to evaluate the therapeutic efficacy of Aloe vera-coated curcumin encapsulated nanoparticles in mitigating Alzheimer’s disease progression in mice, by examining behavioural changes, biochemical markers, and histopathological alterations, thus elucidating its potential as a treatment strategy. Methods The green synthesis method was used to synthesise this nanoformulation, which was then characterised using a variety of techniques, including percentage encapsulation efficacy, UV-visible spectroscopy, DLS, FT-IR, FESEM, and EDX. Several in-vivo assessments, including behavioural evaluations, dose optimisation studies, oxidative stress marker estimation, and histological studies, were conducted to determine the potential therapeutic impact of nanoformulation on the Alzheimer-induced mice model. Results The synthesised nanoparticles show a mean diameter of 76.12 nm ±1.23, a PDI of 0.313 ± 0.02, a zeta potential of 6.27 ± 0.65 mV, and the percentage encapsulation efficiency between 90% and 95% indicating good stability of synthesised nanoformulation. With the help of Morris water maze, Y-maze, and novel object recognition assay, the learning capacity and memory were assessed, and the results show that the synthesised nanoformulation significantly decreased the transfer latency to reach baited arm or to the hidden platform within 7 days. Conclusion The formulation demonstrated significant biochemical benefits and remarkable cognitive advantages, establishing it as a prospective therapeutic intervention option that is both safe and effective.

NHE1 Protein in Repetitive Mild TBI-Mediated Neuroinflammation and Neurological Function Impairment.

Mild traumatic brain injuries (mTBIs) are highly prevalent and can lead to chronic behavioral and cognitive deficits often associated with the development of neurodegenerative diseases. Oxidative stress and formation of reactive oxygen species (ROS) have been implicated in mTBI-mediated axonal injury and pathogenesis. However, the underlying mechanisms and contributing factors are not completely understood. In this study, we explore these pathogenic mechanisms utilizing a murine model of repetitive mTBI (r-mTBI) involving five closed-skull concussions in young adult C57BL/6J mice. We observed a significant elevation of Na+/H+ exchanger protein (NHE1) expression in GFAP+ reactive astrocytes, IBA1+ microglia, and OLIG2+ oligodendrocytes across various brain regions (including the cerebral cortex, corpus callosum, and hippocampus) after r-mTBI. This elevation was accompanied by astrogliosis, microgliosis, and the accumulation of amyloid precursor protein (APP). Mice subjected to r-mTBI displayed impaired motor learning and spatial memory. However, post-r-mTBI administration of a potent NHE1 inhibitor, HOE642, attenuated locomotor and cognitive functional deficits as well as pathological signatures of gliosis, oxidative stress, axonal damage, and white matter damage. These findings indicate NHE1 upregulation plays a role in r-mTBI-induced oxidative stress, axonal damage, and gliosis, suggesting NHE1 may be a promising therapeutic target to alleviate mTBI-induced injuries and restore neurological function.

Moderate aerobic training enhances the effectiveness of insulin therapy through hypothalamic IGF1 signaling in rat model of Alzheimer's disease

Alzheimer's disease (AD) is a neurological condition that is connected with a decline in a person's memory as well as their cognitive ability. One of the key topics of AD research has been the exploration of metabolic causes. We investigated the effects of treadmill exercise and intranasal insulin on learning and memory impairment and the expression of IGF1, BDNF, and GLUT4 in hypothalamus. The animals were put into 9 groups at random. In this study, we examined the impact of insulin on spatial memory in male Wistar rats and analyzed the effects of a 4-week pretreatment of moderate treadmill exercise and insulin on the mechanisms of improved hypothalamic glucose metabolism through changes in gene and protein expression of IGF1, BDNF, and GLUT4. We discovered that rat given Aβ25–35 had impaired spatial learning and memory, which was accompanied by higher levels of Aβ plaque burden in the hippocampus and lower levels of IGF1, BDNF, and GLUT4 mRNA and protein expression in the hypothalamus. Additionally, the administration of exercise training and intranasal insulin results in the enhancement of spatial learning and memory impairments, the reduction of plaque burden in the hippocampus, and the enhancement of the expression of IGF1, BDNF, and GLUT4 in the hypothalamus of rats that were treated with Aβ25–35. Our results show that the improvement of learning and spatial memory due to the improvement of metabolism and upregulation of the IGF1, BDNF, and GLUT4 pathways can be affected by pretreatment exercise and intranasal insulin.

Artificial intelligence for library and information science education: using mnemonics to improve learning and retention

Purpose This paper aims to familiarize students and instructors in the field of library and information science (LIS) with some features and benefits of mnemonics in the context of learning artificial intelligence (AI). Design/methodology/approach A narrative review among literature exists on mnemonics, AI and library services. Findings In the field of LIS, the use of mnemonics can be highly beneficial for both students and instructors. Mnemonics can aid in the retention and recall of complex concepts, classification systems, information retrieval strategies, jargon learning and library memory that are fundamental to the field. In the field of AI, mnemonics can be a valuable tool for students learning complex algorithms, concepts and techniques. Mnemonics can help students remember key components of AI models, understand the underlying principles and apply them effectively in problem-solving. Originality/value To the best of the authors’ knowledge, this paper is among the first ones exploring the use of mnemonics for learning subject areas related to artificial intelligence in LIS.

Exploring the multifaceted therapeutic mechanism of Schisanlactone E (XTS) in APP/PS1 mouse model of Alzheimer's disease through multi-omics analysis.

Schisanlactone E, also known as XueTongSu (XTS), is an active compound extracted from the traditional Tujia medicine Kadsura heteroclita ("XueTong"). Recent studies highlight its anti-inflammatory and antioxidant properties, yet the mechanisms of XTS's therapeutic effects on Alzheimer's disease (AD) are unclear. This study aims to elucidate the therapeutic efficacy and mechanisms of XTS in AD. Ten C57BL/6 mice were assigned to the control group (NC), and twenty APP/PS1 transgenic mice were randomly divided into the model group (M) (10 mice) and the XTS treatment group (Tre) (10 mice). After an acclimatization period of 7 days, intraperitoneal injections were administered over a 60-day treatment period. The NC and M groups received saline, while the Tre group received XTS at 2 mg/kg. Learning and memory abilities were assessed using the Morris Water Maze (MWM) test. Histopathological changes were evaluated using hematoxylin and eosin (HE) and Nissl staining, and immunofluorescence was used to assess pathological products and glial cell activation. Cytokine levels (IL-1β, IL-6, TNF-α) in the hippocampus were quantified by qPCR. 16S rDNA sequencing analyzed gut microbiota metabolic alterations, and metabolomic analysis was performed on cortical samples. The KEGG database was used to analyze the regulatory mechanisms of XTS in AD treatment. XTS significantly improved learning and spatial memory in APP/PS1 mice and ameliorated histopathological changes, reducing Aβ plaque aggregation and glial cell activation. XTS decreased the expression of inflammatory cytokines IL-1β, IL-6, and TNF-α. It also enhanced gut microbiota diversity, notably increasing Akkermansia species, and modulated levels of metabolites such as isosakuranetin, 5-KETE, 4-methylcatechol, and sphinganine. Pathway analysis indicated that XTS regulated carbohydrate metabolism, neuroactive ligand-receptor interactions, and alanine, aspartate, and glutamate metabolism, mitigating gut microbiota dysbiosis and metabolic disturbances. XTS ameliorates cognitive deficits, pathological changes, and inflammatory responses in APP/PS1 mice. It significantly modulates the gut microbiota, particularly increasing Akkermansia abundance, and influences levels of key metabolites in both the gut and brain. These findings suggest that XTS exerts anti-AD effects through the microbial-gut-brain axis (MGBA).

Cerebellar output neurons impair non-motor behaviors by altering development of extracerebellar connectivity.

The capacity of the brain to compensate for insults during development depends on the type of cell loss, whereas the consequences of genetic mutations in the same neurons are difficult to predict. We reveal powerful compensation from outside the cerebellum when the excitatory cerebellar output neurons are ablated embryonically and demonstrate that the minimum requirement for these neurons is for motor coordination and not learning and social behaviors. In contrast, loss of the homeobox transcription factors Engrailed1/2 (EN1/2) in the cerebellar excitatory lineage leads to additional deficits in adult learning and spatial working memory, despite half of the excitatory output neurons being intact. Diffusion MRI indicates increased thalamo-cortico-striatal connectivity in En1/2 mutants, showing that the remaining excitatory neurons lacking En1/2 exert adverse effects on extracerebellar circuits regulating motor learning and select non-motor behaviors. Thus, an absence of cerebellar output neurons is less disruptive than having cerebellar genetic mutations.

Cognitive impairment in major depressive disorder with non-suicidal self-injury: Association with the functional connectivity of frontotemporal cortex

BackgroundNon-suicidal self-injury (NSSI) may be related to serious cognitive impairment in patients with major depressive disorder (MDD), but the specific mechanism is still unclear. This study attempts to identify the neurobiological process alterations of cognitive impairment in MDD patients with NSSI by examining the functional connectivity of the frontotemporal cortex in MDD patients with or without NSSI. MethodThirty MDD patients with NSSI, 36 MDD patients without NSSI, and 35 healthy controls (HC) were included in the study. The MATRICS Consensus Cognitive Battery (MCCB) was used to comprehensively assess the cognitive function of the subjects and functional near-infrared spectroscopy (fNIRS) was used to detect the functional connectivity of the frontotemporal cortex and its brain regions of interest. ResultsMDD patients with or without NSSI had multi-domain cognitive impairments. MDD patients with NSSI showed the lowest score in performance of attention/alertness and the weakest functional connectivity of frontotemporal when compared with the MDD patients without NSSI and the HC. In addition, the functional connectivity of the bilateral frontotemporal cortex was positively correlated with verbal learning and working memory in MDD patients with NSSI. ConclusionIn MDD patients, the appearance of NSSI is often accompanied by further impairment of attention/alertness and a decline in functional connectivity of the frontotemporal cortex. The impairment of verbal learning and working memory was associated with decreased functional connectivity of the frontotemporal cortex in MDD patients with NSSI.

The role of sleep in the link between cannabis use and memory function: evidence from a cross-sectional study

ABSTRACT Background: It is known that cannabis use affects memory and sleep problems independently. However, to date, how memory and sleep problems may interact as a result of cannabis use remains unknown. Objectives: We performed a secondary analysis of existing data to determine whether sleep quality mediates the association between cannabis use and memory and whether sex moderated these effects. Methods: A total of 141 adults with cannabis use disorder (CUD) (83 men) and 87 without CUD (39 men) participated in this study. Outcome measures included self-reported sleep problems from the past 7 days (Marijuana Withdrawal Checklist), learning and memory performance via the short visual object learning task (sVOLT), short visual object learning task delayed (sVOLTd), and verbal memory via the N-back. Bootstrapped mediation and moderated mediation analyses were run to test if sleep quality mediated the association between cannabis use and memory outcomes and whether sex moderated these effects, respectively. Results: Sleep quality mediated the effect of group (i.e. adults with and without CUD) on sVOLT efficiency scores (indirect effect ß = −.08, 95% CI [−0.14, −0.04]) and sVOLTd efficiency scores (indirect effect ß = −.09, 95% CI [−0.14, −0.04]), where greater sleep difficulties was associated with poorer memory performance (decreased efficiency scores). Sex did not moderate these relationships. Conclusion: These initial findings of a mediating role of sleep in the association between CUD and visual learning memory highlight potential critical downstream effects of disrupted sleep in those with CUD and suggest the importance of investigating sleep in CUD.

Huanglian Wendan Decoction Improves Insomnia in Rats by Regulating BDNF/TrkB Signaling Pathway Through Gut Microbiota-Mediated SCFAs and Affecting Microglia Polarization.

Insomnia is a typical type of sleep disorder. Huanglian Wendan Decoction (HWD) is a traditional Chinese medicine (TCM) with the effects of regulating Qi, drying dampness and resolving phlegm, calming the mind, and relieving irritation. This study aims to investigate the effect of HWD on insomnia in rats and its mechanism. Para-chlorophenylalanine (PCPA)-induced insomnia in rats was used for in vivo experiments and then treated with HWD. Behavioral tests, Western blot, real-time PCR, immunofluorescent staining, 16S rRNA sequencing were conducted. The content of SCFAs was determined by GC-MS. Acetic acid-pretreated rat hippocampal nerve cells were used for in vitro experiments. The results showed that HWD significantly improved the learning memory ability, decreased sleep latency, and prolonged sleep duration in insomniac rats. HWD reduced TNF-α and IL-6 levels and increased IL-10 and Foxp3 levels. HWD also promoted the polarization of macrophages from M1 pro-inflammatory phenotype to M2 anti-inflammatory phenotype. In addition, HWD increased the expression levels of BDNF and TrkB in the hippocampus. Administration of the TrkB receptor agonist 7,8-dihydroxyflavone (7,8-DHF) confirmed the mechanism by which HWD activates BDNF/TrkB signaling to ameliorate insomnia. Furthermore, HWD restored gut microbiota richness and diversity and promoted short-chain fatty acid (SCFA) production in insomniac rats. In vitro experiments confirmed that the acetic acid-treated SCFA group could activate the BDNF/TrkB signaling pathway in neuronal cells, further promoting neuronal cell growth. In conclusion, HWD alleviated insomnia by maintaining gut microbiota homeostasis, promoting SCFA production, reducing neuroinflammatory response and microglia activation, and activating BDNF/TrkB signaling pathway.

Intermittent hypoxia exacerbates anxiety in high-fat diet-induced diabetic mice by inhibiting TREM2-regulated IFNAR1 signaling

BackgroundType 2 diabetes mellitus (T2DM) and obstructive sleep apnea (OSA) are mutual risk factors, with both conditions inducing cognitive impairment and anxiety. However, whether OSA exacerbates cognitive impairment and anxiety in patients with T2DM remains unclear. Moreover, TREM2 upregulation has been suggested to play a protective role in attenuating microglia activation and improving synaptic function in T2DM mice. The aim of this study was to explore the regulatory mechanisms of TREM2 and the cognitive and anxiety-like behavioral changes in mice with OSA combined with T2DM.MethodsA T2DM with OSA model was developed by treating mice with a 60% kcal high-fat diet (HFD) combined with intermittent hypoxia (IH). Spatial learning memory capacity and anxiety in mice were investigated. Neuronal damage in the brain was determined by the quantity of synapses density, the number and morphology of brain microglia, and pro-inflammatory factors. For mechanism exploration, an in vitro model of T2DM combined with OSA was generated by co-treating microglia with high glucose (HG) and IH. Regulation of TREM2 on IFNAR1-STAT1 pathway was determined by RNA sequencing and qRT-PCR.ResultsOur results showed that HFD mice exhibited significant cognitive dysfunction and anxiety-like behavior, accompanied by significant synaptic loss. Furthermore, significant activation of brain microglia and enhanced microglial phagocytosis of synapses were observed. Moreover, IH was found to significantly aggravate anxiety in the HFD mice. The mechanism of HG treatment may potentially involve the promotion of TREM2 upregulation, which in turn attenuates the proinflammatory microglia by inhibiting the IFNAR1-STAT1 pathway. Conversely, a significant reduction in TREM2 in IH-co-treated HFD mice and HG-treated microglia resulted in the further activation of the IFNAR1-STAT1 pathway and consequently increased proinflammatory microglial activation.ConclusionsHFD upregulated the IFNAR1-STAT1 pathway and induced proinflammatory microglia, leading to synaptic damage and causing anxiety and cognitive deficits. The upregulated TREM2 inT2DM mice brain exerted a negative regulation of the IFNAR1-STAT1 pathway. Mice with T2DM combined with OSA exacerbated anxiety via the downregulation of TREM2, causing heightened IFNAR1-STAT1 pathway activation and consequently increasing proinflammatory microglia.Graphical

Hippocampus Oxytocin Signaling Promotes Prosocial Eating in Rats

BackgroundOxytocin (OT) is a hypothalamic neuropeptide involved in diverse physiological and behavioral functions, including social-based behavior and food intake control. The extent to which OT’s role in regulating these 2 fundamental behaviors is interconnected is unknown, which is a critical gap in knowledge given that social factors have a strong influence on eating behavior in mammals. Here, we focus on OT signaling in the dorsal hippocampus (HPCd), a brain region recently linked to eating and social memory, as a candidate system where these functions overlap. MethodsHPCd OT signaling gain- and loss-of-function strategies were used in male Sprague Dawley rats that were trained in a novel social eating procedure to consume their first nocturnal meal under conditions that varied with regard to conspecific presence and familiarity. The endogenous role of HPCd OT signaling was also evaluated for olfactory-based social transmission of food preference learning, sociality, and social recognition memory. ResultsHPCd OT administration had no effect on food intake under isolated conditions but significantly increased consumption in the presence of a familiar but not an unfamiliar conspecific. Supporting these results, chronic knockdown of HPCd OT receptor expression eliminated the food intake–promoting effects of a familiar conspecific. HPCd OT receptor knockdown also blocked social transmission of food preference learning and impaired social recognition memory without affecting sociality. ConclusionsCollectively, the results of the current study identify endogenous HPCd OT signaling as a novel substrate in which OT synergistically influences eating and social behaviors, including the social facilitation of eating and the social transmission of food preference.