Impaired Long-term Memory Research Articles

The Effect оf Repeated Exposure to Complexly Organized Electromagnetic Radiation on the Rats Behavior in the “Open Field” Test

In experiments on Wistar rats, males and females, the effect of 3-fold (1 hour a day with an interval of three days) and multiple (8 weeks, 5 days a week, 2 hours a day) pulsed-modulated electromagnetic radiation on the tentative research reactions was studied, tested by the “open field” method. The animals were irradiated in an anechoic chamber in the zone of the formed wave of the microwave source (a block of 10 generators carrying frequencies from 1 to 4 GHz, the total pulse power density 300 microW/cm2, pulse duration 25 ms, sweep cycles 1–6 Hz, cycle turn-around time 30s). It has been showed that exposure to such parameters can cause a stress reaction and an impairment of long-term memory in some irradiated animals, and female rats were more sensitive to the action of microwaves, than males. This reaction was transient and 1.5–2 months after cessation of irradiation, the behavior of the animals was restored. However, there is a danger that with constant exposure to microwaves, which, for example, occurs in mobile users, such behavior deviations may become fixed and clinically significant.

Who is at risk of long-term subjective memory impairment after electroconvulsive therapy?

Electroconvulsive therapy (ECT) is an effective treatment for depression with potential transient cognitive side effects. However, subjective memory impairment can extend over a long period after ECT. This study aimed to assess potential risk factors for long-term subjective memory impairment 6 months after ECT and to explore if the associations are mediated by depressive symptoms. This registry-based study used the Swedish National Quality Register for ECT and other national registers. Long-term subjective memory worsening was defined as a minimum 2-step worsening on the memory item from the comprehensive psychopathological rating scale (CPRS-M) from before ECT to 6 months after ECT. Changes on the scale were also analyzed in continuous models. Statistical methods used were logistic regression and linear regression analyses in univariable and multivariable models. The study population consisted of 1498 patients. Subjective memory worsening occurred in 25.2 % of the population. Long-term subjective memory worsening was associated with more depressive symptoms and lower education levels. No association could be found related to ECT technical factors. The associations between age and psychiatric comorbidities with subjective memory worsening were mediated by depressive symptoms. Patients can be informed that depressive symptoms are one of the biggest contributing factors to long-term subjective memory impairment after ECT. A successful treatment is therefore important to minimize the long-term experience of memory deficits. The number of sessions or ECT technical factors do not seem to be associated with long-term subjective memory impairment.

Temporal differential effects of post-injury alcohol consumption in a mouse model of blast-induced traumatic brain injury

Traumatic brain injury is a prevalent condition that affects millions worldwide with no clear understanding or effective therapeutic management available. Military soldiers have a high risk of exposure to blast-induced traumatic brain injury (bTBI). Furthermore, alcohol drinking is common in this population, and studies have shown that post-TBI alcohol exposure can result in memory loss. Hence, it is possible that alcohol could contribute to the overall pathological outcome of brain trauma. However, such a possibility has not been explored in detail. Here, we combined a mild bTBI (mbTBI) model with the drinking-in-the-dark (DID) paradigm to investigate the pathological synergy between mbTBI and alcohol consumption by examining brain oxidative stress levels and behavioral alterations in mice. The results revealed the anxiolytic and short-term memory improvement effects of post-trauma alcohol drinking examined at an early timepoint post mbTBI. However, extended alcohol drinking for up to three weeks post mbTBI impaired long-term memory and was accompanied by intensified oxidative stress in brain regions associated with memory and anxiety. These findings, as well as those from previous in vitro TBI/alcohol studies, suggest a pathological synergy of physical force and post-impact alcohol exposure. This knowledge could potentially aid in establishing guidelines for TBI victims to avoid further injury to their brains as well as to help maximize their recovery following TBI.

Neuropsychological performances and brain perfusion patterns in patients with first episode psychosis

Abnormalities in cognition are a pronounced feature in primary psychotic disorders and may appear long before the manifestation of the first-episode psychosis (FEP). Although brain functional changes may precede structural alterations, brain perfusion patterns in FEP and most importantly their correlations with cognition remain poorly understood. In the present study we assessed neurocognitive functions and regional cerebral blood flow (rCBF) in 53 patients with a diagnosis of FEP. A special emphasis was placed on the assessment of basic executive functions. Cerebral perfusion patterns were measured by SPECT rCBF scintigraphy in cerebral lobes bilaterally and Brodmann Areas (BAs).Patients showed impairments in long-term verbal memory, processing speed/response latency and executive cognition. Pathological perfusion was prominent in the limbic lobes bilaterally. BAs with the largest hypoperfusion, were the subgenual area (BA25) and hippocampal areas (BA 28 and 36). The left temporal lobe was also hypoperfused, and specifically the inferior temporal gyrus (BA 20), the left middle (BA 21) and superior (BA 22) temporal gyrus, and the temporal pole (BA 38). Hypoperfusion was limited in the frontal regions, although specific BAs displayed pathological perfusion (i.e., BA 24). Cerebral lobe perfusion was not correlated with compromised cognitive abilities.

Sevoflurane exposure in early life: mitochondrial dysfunction and neurotoxicity in immature rat brains without long-term memory loss

Neurotoxic effects of general anesthetics, particularly sevoflurane, on pediatric neurodevelopment are a global concern. This study investigated the molecular and metabolic impacts of repeated short exposures to sevoflurane in neonatal rats. Metabolomics analysis revealed significant changes in fatty acid and mitochondrial energy metabolism. Transcriptomic analysis identified altered gene expression related to neurodevelopment and mitochondrial function. Various analyses emphasized upregulation in oxidative phosphorylation and DNA repair pathways. Weighted gene co-expression network analysis (WGCNA) identified key gene modules associated with sevoflurane exposure. Despite these acute changes, no significant long-term memory impairments were detected. These findings highlight the impact of sevoflurane on mitochondrial energy metabolism, oxidative stress, and neuroinflammation, emphasizing its relevance to pediatric neurodevelopment. The absence of substantial long-term memory impairments provides insights into the safety and implications of sevoflurane use in pediatric anesthesia, calling for further research.

Diminished lactate utilization in LDHB-deficient neurons leads to impaired long-term memory retention

Neurons' high energy demands for processing, transmitting, and storing information in the brain necessitate efficient energy metabolism to maintain normal neuronal function. The astrocyte-neuron lactate shuttle (ANLS) hypothesis suggests neurons preferentially use lactate from astrocytes over glucose for energy. This study investigated lactate dehydrogenase B (LDHB), which preferentially converts lactate to pyruvate, in neuronal energy metabolism and cognitive function. LDHB-deficient neurons showed reduced lactate-driven energy metabolism in culture, while LDHB-deficient brains accumulated lactate, both indicating decreased lactate utilization. This reduced lactate utilization was correlated with impaired long-term memory in LDHB-deficient mice, while short-term memory remained unaffected and overall neuropathology was only mildly disturbed. Unexpectedly, LDHB-deficient neurons maintain stable energy metabolism under physiological glucose conditions, indicating the presence of lactate dehydrogenase (LDH) activity in LDHB-deficient neurons. The observation of lactate dehydrogenase A (LDHA), which preferentially converts pyruvate to lactate but can also catalyze the reverse reaction less efficiently, in LDHB-deficient neurons may explain their stable energy metabolism and reduced lactate utilization. This study challenges the established concept of strict LDH isoform compartmentalization in brain cells, questioning the exclusive presence of LDHB in neurons and suggesting a more flexible neuronal metabolic profile than previously assumed by the ANSL hypothesis.

Acute Paraoxon-Induced Neurotoxicity in a Mouse Survival Model: Oxidative Stress, Dopaminergic System Alterations and Memory Deficits.

The secondary neurotoxicity induced by severe organophosphorus (OP) poisoning, including paraoxon (POX), is associated with cognitive impairments in survivors, who, despite receiving appropriate emergency treatments, may still experience lasting neurological deficits. Thus, the present study provides a survival mouse model of acute and severe POX poisoning to examine secondary neurotoxicity. Swiss CD-1 male mice were injected with POX (4 mg/kg, s.c.) followed by atropine (4 mg/kg, i.p.), pralidoxime (2-PAM; Pyridine-2-aldoxime methochloride) (25 mg/kg, i.p., twice, 1 h apart) and diazepam (5 mg/kg, i.p.), resulting in a survival rate >90% and Racine score of 5-6. Our results demonstrated that the model showed increased lipid peroxidation, downregulation of antioxidant enzymes and astrogliosis in the mouse hippocampus (HP) and prefrontal cortex (PFC), brain areas involved in cognitive functions. Moreover, dopamine (DA) levels were reduced in the hp, but increased in the PFC. Furthermore, the survival mouse model of acute POX intoxication did not exhibit phenotypic manifestations of depression, anxiety or motor incoordination. However, our results demonstrated long-term recognition memory impairments, which are in accordance with the molecular and neurochemical effects observed. In conclusion, this mouse model can aid in researching POX exposure's effects on memory and developing potential countermeasures against the secondary neurotoxicity induced by severe OP poisoning.

Exposure to Sunset Yellow FCF since post-weaning causes hippocampal structural changes and memory impairment in the adult rat: The neuroprotective effects of Coenzyme Q10.

This study aimed to investigate whether exposure to Sunset Yellow FCF (SY) since post-weaning can lead to hippocampal structural changes and memory impairment in adult rat and whether the Coenzyme Q10 (CoQ10) can protect against these adverse effects. The weanling rats were randomly divided into six groups and were treated daily by oral gavage for 6 weeks, as follows: (I) control group, administered distilled water (0.3mL/100 g/day); (II) CoQ10 group, received 10mg/kg/day CoQ10; (III) low SY group, received 2.5mg/kg/day SY; (IV) high SY group, received 70 mg/kg/day SY; (V) low SY + CoQ10 group; and (VI) high SY + CoQ10 group. At the end of the sixth week, the novel object recognition (NOR) test was conducted to evaluate memory. Then, after sacrificing animals, the cerebral hemispheres were removed for stereological study and evaluation of MDA levels. The low and high doses of SY led to significant neuronal loss and a decrease in the volume of the hippocampus (CA1 and DG subregions), as well as increased the MDA level, which was associated with short- and long-term memory impairment. Although, administration of CoQ10 prevented the hippocampal neural loss and volume, and caused a reduction in MDA and improved memory in the low and high SY groups. It seems that CoQ10 could prevent the neuronal loss and hippocampal atrophy caused by post-weaning exposure to SY through preventing oxidative stress, ultimately improving memory impairment in rats.

Neuropharmacological Assessment of Sulfonamide Derivatives of Para-Aminobenzoic Acid through In Vivo and In Silico Approaches

Background/Objectives: Alzheimer’s disease (AD), a complex neurogenerative disorder, manifests as dementia and concomitant neuropsychiatric symptoms, including apathy, depression, and circadian disruption. The pathology involves a profound degeneration of the hippocampus and cerebral cortex, leading to the impairment of both short-term and long-term memory. The cholinergic hypothesis is among the various theories proposed, that assume the loss of the cholinergic tract contributes to the onset of AD and proves clinically effective in managing mild to moderate stages of the disease. This study explores the potential therapeutic efficacy of sulfonamide-based butyrylcholinesterase inhibitors in mitigating scopolamine-induced amnesia in rats. Methods: Behavioral assessments utilizing Y-maze, Barnes maze, and neurochemical assays were conducted to evaluate the effectiveness of the test compounds. Results: Results demonstrated a significant reduction in the impact of scopolamine administration on behavioral tasks at a dose of 20 mg/kg for both compounds. Correspondingly, neurochemical assays corroborated these findings. In silico docking analysis on rat butyrylcholinesterase (BChE) was performed to elucidate the binding mode of the compounds. Subsequent molecular dynamics studies unveiled the formation of stable complexes between the test compounds and rat BChE. Conclusions: These findings contribute valuable insights into the potential therapeutic role of sulfonamide-based butyrylcholinesterase inhibitors in addressing memory deficits associated with AD, emphasizing their in silico molecular interactions and stability.

N-Pep-Zn Improves Cognitive Functions and Acute Stress Response Affected by Chronic Social Isolation in Aged Spontaneously Hypertensive Rats (SHRs).

Aging and chronic stress are regarded as the most important risk factors of cognitive decline. Aged spontaneously hypertensive rats (SHRs) represent a suitable model of age-related vascular brain diseases. The aim of this study was to explore the effects of chronic isolation stress in aging SHRs on their cognitive functions and response to acute stress, as well as the influence of the chronic oral intake of N-Pep-Zn, the Zn derivative of N-PEP-12. Nine-month-old SHRs were subjected to social isolation for 3 months (SHRiso group), and one group received N-pep-Zn orally (SHRisoP, 1.5 mg/100 g BW). SHRs housed in groups served as the control (SHRsoc). The behavioral study included the following tests: sucrose preference, open field, elevated plus maze, three-chamber sociability and social novelty and spatial learning and memory in a Barnes maze. Levels of corticosterone, glucose and proinflammatory cytokines in blood plasma as well as salivary amylase activity were measured. Restraint (60 min) was used to test acute stress response. Isolation negatively affected the SHRs learning and memory in the Barnes maze, while the treatment of isolated rats with N-Pep-Zn improved their long-term memory and working memory impairments, making the SHRisoP comparable to the SHRsoc group. Acute stress induced a decrease in the relative thymus weight in the SHRiso group (but not SHRsoc), whereas treatment with N-Pep-Zn prevented thymus involution. N-pep-Zn mitigated the increment in blood cortisol and glucose levels induced by acute stress. N-pep-Zn enhanced the adaptive capabilities towards chronic (isolation) and acute (immobilization) stress in aged SHRs and prevented cognitive disturbances induced by chronic isolation, probably affecting the hypothalamo-pituitary-adrenal, sympathetic, and immune systems.

HCN channel-dependent presynaptic potentiation at LA-BA synapses is required for fear memory formation

Previously, we demonstrated that auditory fear conditioning produces presynaptic potentiation at lateral to basal amygdala (LA-BA) synapses, which occludes high-frequency stimulation (HFS)-induced ex-vivo LTP. We also found that the HFS-induced ex-vivo LTP requires presynaptic hyperpolarization-activated cyclic nucleotide-gated (HCN) channel activity. In this study, we investigated whether HCN channels are necessary for auditory fear conditioning in vivo. Our results show that ZD7288, an HCN channel blocker, reduced synaptic transmission and decreased the paired pulse ratio (PPR) only in slices from rats that underwent auditory fear conditioning, but not from naïve rats. This indicates that fear conditioning involves HCN channel-dependent presynaptic potentiation at LA-BA synapses. Importantly, injecting ZD7288 into the basal amygdala (BA) before auditory fear conditioning significantly impaired long-term fear memory formation. Since HCN channel activity is necessary for LTP at LA-BA synapses but not at cortico-BA, cortico-LA, or thalamo-LA synapses, HCN channel-dependent presynaptic potentiation at LA-BA synapses appears to be crucial for auditory fear conditioning.

Impact of levetiracetam and ethanol on memory, selected neurotransmitter levels, oxidative stress parameters, and essential elements in rats

BackgroundEthanol disrupts brain activity and memory. There is evidence supporting the beneficial effect of levetiracetam on alcohol consumption. Therefore, the aim of the study was to examine whether levetiracetam has a protective activity against ethanol-induced memory impairment, alterations in selected neurotransmission activities, oxidative stress, and selected essential elements in rats.MethodsThe rats were given levetiracetam (300 mg/kg b.w. po) with ethanol for three weeks prior to behavioral tests. Spatial memory was tested using the Morris water maze, while recognition memory was evaluated using the Novel object recognition test. The GABA and glutamate concentration was determined in three rat brain regions (cerebellum, hippocampus, and cerebral cortex). Serum oxidative stress parameters and selected essential elements concentration (Cu, Mn, Zn, Fe, Mg) in the rat brain were analyzed.ResultsLevetiracetam administered with ethanol improved spatial memory, but did not affect abstinence-induced impairment. The drug also decreased ethanol-induced long-term recognition memory impairment. No alterations in glutamate levels were observed. GABA levels were elevated by levetiracetam in the cerebral cortex and by ethanol in the cerebellum. Ethanol increased catalase activity (CAT) and decreased superoxide dismutase activity (SOD) in the serum. Levetiracetam significantly increased the activity of SOD. Alcohol disrupted the levels of trace elements (Mn, Zn, Mg) in the rat brain. Additionally, levetiracetam alone increased Mg, Fe, and Cu concentrations while all animals receiving the drug also had significantly lower concentrations of Zn.ConclusionsLevetiracetam had differential effects against ethanol-induced impairments. These findings could have important implications for future levetiracetam treatment in patients.

Hippocampal hub failure is linked to long-term memory impairment in anti-NMDA-receptor encephalitis: insights from structural connectome graph theoretical network analysis

BackgroundAnti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is characterized by distinct structural and functional brain alterations, predominantly affecting the medial temporal lobes and the hippocampus. Structural connectome analysis with graph-based investigations of network properties allows for an in-depth characterization of global and local network changes and their relationship with clinical deficits in NMDAR encephalitis.MethodsStructural networks from 61 NMDAR encephalitis patients in the post-acute stage (median time from acute hospital discharge: 18 months) and 61 age- and sex-matched healthy controls (HC) were analyzed using diffusion-weighted imaging (DWI)-based probabilistic anatomically constrained tractography and volumetry of a selection of subcortical and white matter brain volumes was performed. We calculated global, modular, and nodal graph measures with special focus on default-mode network, medial temporal lobe, and hippocampus. Pathologically altered metrics were investigated regarding their potential association with clinical course, disease severity, and cognitive outcome.ResultsPatients with NMDAR encephalitis showed regular global graph metrics, but bilateral reductions of hippocampal node strength (left: p = 0.049; right: p = 0.013) and increased node strength of right precuneus (p = 0.013) compared to HC. Betweenness centrality was decreased for left-sided entorhinal cortex (p = 0.042) and left caudal middle frontal gyrus (p = 0.037). Correlation analyses showed a significant association between reduced left hippocampal node strength and verbal long-term memory impairment (p = 0.021). We found decreased left (p = 0.013) and right (p = 0.001) hippocampal volumes that were associated with hippocampal node strength (left p = 0.009; right p < 0.001).ConclusionsFocal network property changes of the medial temporal lobes indicate hippocampal hub failure that is associated with memory impairment in NMDAR encephalitis at the post-acute stage, while global structural network properties remain unaltered. Graph theory analysis provides new pathophysiological insight into structural network changes and their association with persistent cognitive deficits in NMDAR encephalitis.

Sleep deprivation in adolescent mice impairs long-term memory till early adulthood via suppression of hippocampal astrocytes.

Sleep deficiency is a rampant issue in modern society, serving as a pathogenic element contributing to learning and memory impairment, with heightened sensitivity observed in children. Clinical observations suggest that learning disabilities associated with insufficient sleep during adolescence can persist through adulthood, but experimental evidence for this is lacking. In this study, we examined the impact of early-life sleep deprivation (SD) on both short-term and long-term memory, tracking the effects sequentially into adulthood. We employed a modified multiple-platform method mouse model to investigate these outcomes. SD induced over a 14-day period, beginning on postnatal day 28 (PND28) in mice, led to significant impairment in long-term memory (while short-term memory remained unaffected) at PND42. Notably, this dysfunction persisted into adulthood at PND85. The specific impairment observed in long-term memory was elucidated through histopathological alterations in hippocampal neurogenesis, as evidenced by bromodeoxyuridine (BrdU) signals, observed both at PND42 and PND85. Furthermore, the hippocampal region exhibited significantly diminished protein expressions of astrocytes, characterized by lowered levels of aquaporin 4 (AQP4), a representative molecule involved in brain clearance processes, and reduced protein expressions of brain-derived neurotrophic factors. In conclusion, we have presented experimental evidence indicating that sleep deficiency-related impairment of long-term memory in adolescence can endure into adulthood. The corresponding mechanisms may indicate that the modification of astrocyte-related molecules has led to changes in hippocampal neurogenesis.

Chronic Treatment with Oxcarbazepine Attenuates Its Anticonvulsant Effect in the Maximal Electroshock Model in Mice.

The objective of this study was to assess the impact of acute and chronic treatment with oxcarbazepine on its anticonvulsant activity, neurological adverse effects, and protective index in mice. Oxcarbazepine was administered in four protocols: once or twice daily for one week (7 × 1 or 7 × 2) and once or twice daily for two weeks (14 × 1 or 14 × 2). A single dose of the drug was employed as a control. The anticonvulsant effect was evaluated in the maximal electroshock test in mice. Motor and long-term memory impairment were assessed using the chimney test and the passive avoidance task, respectively. The concentrations of oxcarbazepine in the brain and plasma were determined via high-performance liquid chromatography. Two weeks of oxcarbazepine treatment resulted in a significant reduction in the anticonvulsant (in the 14 × 1; 14 × 2 protocols) and neurotoxic (in the 14 × 2 schedule) effects of this drug. In contrast, the protective index for oxcarbazepine in the 14 × 2 protocol was found to be lower than that calculated for the control. No significant deficits in memory or motor coordination were observed following repeated administration of oxcarbazepine. The plasma and brain concentrations of this anticonvulsant were found to be significantly higher in the one-week protocols. Chronic treatment with oxcarbazepine may result in the development of tolerance to its anticonvulsant and neurotoxic effects, which appears to be dependent on pharmacodynamic mechanisms.

Exploring the Potential Role of Lactobacillus plantarum in the Reversal of Induced Cognitive Long-term Memory Impairment

Long-term Memory (LTM) is formed by sequential changes in the different brain regions due to synaptic plasticity changes. This synaptic plasticity changes formed in the brain due to the acquittance of unexposed information and its retrieval due to learning and memory formation (LMF). In a normal condition, LMF uses RNA and protein synthesis machinery to form LTM, which lasts till the end of an organism's lifetime. Formed LTM shows sequential changes happening in the presynaptic and postsynaptic neurons. Stated sequential changes are initiated when the released neurotransmitter binds with the postsynaptic neuronal receptors and activates the brain's ERK - CREB neuronal signaling pathway. Based on the previous findings, the present study was designed to study the interrelationship between cognitive impairment and oral/gut dysbiosis with the help of a probiotic strain (Lactobacillus plantarum). Two phases of behavioural analysis (first and second phase) were used to identify the effect of oral microbial infusions on impaired LTM formation and its reversal using restoration of dysbiosed gut/oral microbiota. The first phase of behavioural analysis (FPBA) reported that oral microbial infusion plays a major role in developing oral/gut dysbiosis, which results in impaired cognitive functions. Further, formed oral/gut microbiota dysbiosis was reversed with the help of probiotic strain in the second phase of behavioural analysis (SPBA). Thus, a comparative two-phase behavioural analysis revealed that probiotics may play a significant role in reversing induced cognitive decline. The outcome of the present study also proved that probiotic treatment might play a major role in the reversal of dysbiosed microbiota in the oral cavity and the gut.

Sepsis compromises post-ischemic stroke neurological recovery and is associated with sex differences

AimsInfection is a complication after stroke and outcomes vary by sex. Thus, we investigated if sepsis affects brain from ischemic stroke and sex involvement. Main methodsMale and female Wistar rats, were submitted to middle cerebral artery occlusion (MCAO) and after 7 days sepsis to cecal ligation and perforation (CLP). Infarct size, neuroinflammation, oxidative stress, and mitochondrial activity were quantified 24 h after CLP in the prefrontal cortex and hippocampus. Survival and neurological score were assessed up to 15 days after MCAO or 8 days after CLP (starting at 2 h after MCAO) and memory at the end. Key findingsCLP decreased survival, increased neurological impairments in MCAO females. Early, in male sepsis following MCAO led to increased glial activation in the brain structures, and increased TNF-α and IL-1β in the hippocampus. All groups had higher IL-6 in both tissues, but the hippocampus had lower IL-10. CLP potentiated myeloperoxidase (MPO) in the prefrontal cortex of MCAO male and female. In MCAO+CLP, only male increased MPO and nitrite/nitrate in hippocampus. Males in all groups had protein oxidation in the prefrontal cortex, but only MCAO+CLP in the hippocampus. Catalase decreased in the prefrontal cortex and hippocampus of all males and females, and MCAO+CLP only increased this activity in males. Female MCAO+CLP had higher prefrontal cortex complex activity than males. In MCAO+CLP-induced long-term memory impairment only in females. SignificanceThe parameters evaluated for early sepsis after ischemic stroke show a worse outcome for males, while females are affected during long-term follow-up.

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

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. 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. 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. 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.

Hyperbaric Oxygen Improves Long-Term Learning and Memory Impairment by Attenuating Neuronal Apoptosis in aMCI Rats.

With the aging of the population and the increasing incidence of neurological diseases, amnestic mild cognitive impairment (aMCI) has attracted attention. Hyperbaric oxygen (HBO) has gradually shown the potential in the treatment of aMCI as an emerging treatment method in recent times. This study is to observe the effect of HBO on the long-term learning memory of aMCI rats, and investigate the associated mechanisms. Seventy-two male rats (4-month-old) were randomly divided into control (CON) group, aMCI group, HBO group, 24 rats in each group. Each group was randomly divided into CON1, CON7, CON28; aMCI1, aMCI7, aMCI28; HBO1, HBO7, HBO28, 8 rats in each group. The aMCI model rats were established in aMCI and HBO groups. HBO group was treated with HBO for 7 days. The ethological and cytopathology which include Morris water maze (MWM) test, HE staining, TUNEL staining and the expression of Fas/FasL on neuron membrane were conducted to evaluate the effects of HBO on day 1, day 7 and day 28 after HBO treatment. MWM test showed that the spatial learning and memory ability of the rats decreased in aMCI group, and recovered in HBO group; Compared with aMCI group, the pathological damage of hippocampal nerve cells was alleviated, the number of apoptotic cells was significantly reduced (P < 0.05), and the expression of Fas/FasL on the surface of nerve cell membrane was significantly weakened in HBO group (P < 0.05). There were no significant changes in the spatial learning and memory ability, pathological damage of hippocampal neurons, the number of apoptotic cells, and the changes of Fas/FasL on the surface of hippocampal neurons in HBO1, HBO7, and HBO28 groups (P > 0.05). However, in aMCI1, aMCI7, and aMCI28 groups gradually aggravated (P < 0.05). 1. HBO can improve the long-term learning and memory impairment by attenuating neuronal apoptosis in aMCI rats. 2. Fas/FasL mediated cell receptor death pathway is involved in the apoptosis of hippocampal neurons.

Pregestational fructose-induced metabolic syndrome in Wistar rats causes sexually dimorphic behavioral changes in their offspring.

Metabolic syndrome (MetS), marked by enduring metabolic inflammation, has detrimental effects on cognitive performance and brain structure, influencing behavior. This study aimed to investigate whether maternal MetS could negatively impact the neurodevelopment and metabolism of offspring. To test this hypothesis, 2 months old female Wistar rats were subjected to a 10-week regimen of tap water alone or supplemented with 20% fructose to induce MetS. Dams were mated with healthy males to generate litters: OC (offspring from control dams) and OMetS (offspring from dams with MetS). To isolate prenatal effects, all pups were breastfed by control nurse dams, maintaining a standard diet and water ad libitum until weaning. Behavioral assessments were conducted between postnatal days (PN) 22 and 95, and metabolic parameters were analyzed post-sacrifice on PN100. Results from the elevated plus maze, the open field, and the marble burying tests revealed a heightened anxiety-like phenotype in OMetS females. The novel object recognition test showed that exclusively OMetS males had long-term memory impairment. In the reciprocal social interaction test, OMetS displayed a lower number of social interactions, with a notable increase in "socially inactive" behavior observed exclusively in females. Additionally, in the three-chamber test, social preference and social novelty indexes were found to be lower solely among OMetS females. An increase in visceral fat concomitantly with hypertriglyceridemia was the relevant postmortem metabolic finding in OMetS females. In summary, maternal MetS leads to enduring damage and adverse effects on offspring neurobehavior and metabolism, with notable sexual dimorphism.