Memory Impairment Research Articles

The Cognitive Restoration Effects of Resveratrol: Insight Molecular through Behavioral Studies in Various Cognitive Impairment Models.

Cognition is essential for daily activities and progressively deteriorates with age due to various factors leading to cognitive decline. This decline often begins with memory impairment and advances to broader cognitive dysfunctions. Resveratrol (RES), a natural phenolic compound found in red wine, has garnered significant attention for its potential to prevent cognitive decline. This review aims to synthesize the latest preclinical data on the cognitive restorative effects of RES. We highlight RES activities from cellular mechanisms to behavioral outcomes. Evidence from various cognitive impairment models demonstrates that RES exerts neuroprotective effects through multiple mechanisms, including anti-inflammatory, antioxidative, anti-apoptotic, and neurotrophic actions, all of which contribute to cognitive enhancement in behavioral studies. Despite the established role of RES in mitigating memory decline, our review identifies a critical gap in behavioral studies regarding cognitive flexibility. Further research in this domain is recommended. Additionally, species-specific pharmacokinetic differences may account for the inconsistencies between preclinical and clinical outcomes, particularly in rats and humans. We propose that formulations designed to delay gut metabolism through enterohepatic circulation could enhance the translational potential of RES. Furthermore, long-term studies are needed to determine the optimal dose capable of maximizing health benefits without raising toxicity during chronic use.

The Contribution of the Face-Name Associative Recognition Test to Objectifying the Impairment of Associative Memory in Subjective Cognitive Decline.

Subjective cognitive decline (SCD) is defined as a self-reported perception of cognitive decline that occurs without clear objective signs of cognitive impairment. There is still uncertainty in the literature about the reliability of SCD as an accurate indicator of the early stages of major neurocognitive disorders. Furthermore, objectifying cognitive impairment in SCD is difficult, mainly due to the insensitivity of the assessment instruments. The main objective of this study was to investigate the potential contribution of the face-name associative recognition test (FNART) to the objective identification of memory impairment in SCD. A research sample of 69 adults with SCD and 69 healthy controls (HCs) recruited in the community were administered in the FNART, which included 32 photographs of neutral faces associated with 32 first names. The total score of the HC group in the FNART was significantly better than that of the SCD group. Moreover, analyses based on the serial position of the stimuli showed that the SCD group performed significantly worse than the HC group only for the middle items (stimuli placed at the beginning or end of learning lists are more likely to be recalled than those presented in the middle), while no primacy and recency effects were found in the HCs. These findings indicate that associative episodic memory is more vulnerable in individuals with subjective cognitive decline (SCD) compared to those without cognitive complaints. Additionally, they suggest that the FNART may be effective in identifying cognitive decline in the preclinical stage of Alzheimer's disease.

Adverse Effects of Aβ1-42 Oligomers: Impaired Contextual Memory and Altered Intrinsic Properties of CA1 Pyramidal Neurons.

Aβ1-42 (amyloid beta) oligomers, the major neurotoxic culprits in Alzheimer's disease, initiate early pathophysiological events, including neuronal hyperactivity, that underlie aberrant network activity and cognitive impairment. Although several synaptotoxic effects have been extensively studied, neuronal hyperexcitability, which may also contribute to cognitive deficits, is not fully understood. Here, we found several adverse effects of in vivo injection of Aβ1-42 oligomers on contextual memory and intrinsic properties of CA1 pyramidal neurons. Male rats underwent behavioral and electrophysiological studies 1 week after microinjections into the dorsal CA1 region, followed by histological analysis. After 1 week, Aβ1-42 oligomers impaired contextual learning without affecting basic physiological functions and triggered training-induced neuronal excitability. Furthermore, riluzole, a persistent sodium current (INaP) blocker, dose-dependently reduced Aβ1-42 oligomer-induced hyperexcitability. Congo red staining, which detects insoluble amyloid deposits, further identified labeling of CA1 pyramidal neurons while immunohistochemistry with lecanemab, which detects soluble Aβ oligomers, revealed immunoreactivity of both pyramidal and non-pyramidal cells in the target area. Therefore, our study suggests that a single injection of Aβ1-42 oligomers resulted in contextual memory deficits along with concomitant neuronal hyperexcitability and amyloid deposition in the CA1 region after 1 week.

Ganoderma lucidum polysaccharide alleviates cognitive dysfunction by inhibiting neuroinflammation via NLRP3/NF-κB signaling pathway

Ethnopharmacological relevanceGanoderma lucidum (G. lucidum), a traditional Chinese medicinal herb, is commonly recommended for its potential to promote mental relaxation and alleviate memory impairment. Recently, there have been reports suggesting that it exhibits anti-neuroinflammatory activity through the gut-brain axis. Cognitive dysfunction is among the most prevalent neurodegenerative diseases. Aim of the studyThis study aimed to investigate the efficacy of polysaccharides extracted from G. lucidum in alleviating cognitive dysfunction. Methods and materialsA polysaccharide was extracted through the process of alkali extraction followed by alcohol precipitation. Comprehensive analysis was conducted to characterize the total sugar content, amino acid composition, and sugar chain structure. The levels of inflammatory related factors were assessed using griess reagent, qPCR and western blotting assay in vitro. The efficacy of alleviating cognitive dysfunction was evaluated through a series of behavioral studies in mice model induced by the high-fat high-sugar diet combined with chronic unpredictable mild stress (HFFD/CUMS) in vivo. The mechanism was investigated by 16S rRNA sequence, immunohistochemistry, flow cytometry and short-chain fatty acid detection. ResultsGanoderma lucidum polysaccharide (GLP) is a polysaccharide identified as β-glucan. Bioactivity experiments have demonstrated that GLP possesses the potential to ameliorate cognitive dysfunction. The mechanism study revealed that GLP can modulate the composition of gut microbiota and suppress the activation of inflammasomes via NLRP3/NF-κB signaling pathway, thereby attenuating neuroinflammatory. Furthermore, GLP may enhance the peripheral immunity response of the body, leading to a comprehensive regulatory effect. ConclusionA polysaccharide alleviates cognitive dysfunction via inhibiting neuroinflammation.

Tetrahedral framework nucleic acids inhibit Aβ-mediated ferroptosis and ameliorate cognitive and synaptic impairments in Alzheimer’s disease

BackgroundFerroptosis represents a nonapoptotic type of programmed cell death induced by excessive intracellular iron accumulation. Ferroptosis is an essential driver of the pathogenesis of Alzheimer’s disease (AD). Tetrahedral framework nucleic acids (tFNAs) are a novel type of nanoparticle with superior antiapoptotic capacity and excellent biocompatibility. However, the effect of tFNAs on Aβ triggered ferroptosis, cognitive and synaptic impairments in AD remains unknown.MethodsN2a cells were treated with Aβ combined with/without tFNAs. Cell viability and levels of Fe2+, lipid peroxidation, MDA, LDH, and GSH were examined. RNA sequencing was applied to explore dysregulated ferroptosis related genes. Seven-month-old APP/PS1 mice were intranasally administrated with tFNAs for two weeks. Fluorescence imaging was used to detect the tFNAs distribution in the brain. Novel object recognition (NOR) test followed by Morris water maze (MWM) was used to test the learning and memory performance of mice. Golgi staining, Western blot, and immunofluorescence staining were used to examine synaptic plasticity.ResultstFNAs promoted cell viability and GSH levels, reduced the levels of Fe2+, lipid peroxidation, MDA, and LDH in N2a cells treated with Aβ. RNA sequencing revealed that tFNAs reversed the promotive effect of Aβ on ferroptosis driver Atf3 gene and suppressive effect on ferroptosis suppressors Rrm2 and Furin genes. Fluorescence imaging confirmed the brain infiltration of tFNAs. tFNAs rescued synaptic and memory impairments, and ferroptosis in seven-month-old APP/PS1 mice.ConclusionsCollectively, tFNAs inhibited Aβ-mediated ferroptosis and ameliorated cognitive and synaptic impairments in AD mice. tFNAs may serve as novel option to deal with AD.Graphical abstract

The effects of deception on memory: a comparative study of actors and eyewitnesses accounts

Deception is a common occurrence in daily life and has been shown to impair memory. This study investigated the memory-undermining effects of deception in a simulated daily life scenario, focusing on the potential moderating effect of the liars’ role (i.e., actor vs. eyewitness). In a 2 × 2 between-subjects design, 128 participants were randomly assigned to one of four conditions: actors who told the truth, actors who lied, eyewitnesses who told the truth, and eyewitnesses who lied. Participants engaged in a simulated shopping task, followed by an interview where they either provided truthful or deceptive responses about the items they bought (actors) or observed (eyewitnesses). Two days later, participants completed a series of memory tests assessing item memory, source memory, destination memory, and non-believed memories. Results showed that deception impaired source memory, with a greater impairment observed for actors than eyewitnesses. Deception also led to more non-believed memories and impaired item and destination memory, regardless of the liars’ role. These findings suggest that the role of liars moderates the effects of deception on memory, with self-related deception (actors) leading to greater memory impairments than other-related deception (eyewitnesses).

Chronic corticosterone exposure causes anxiety- and depression-related behaviors with altered gut microbial and brain metabolomic profiles in adult male C57BL/6J mice

Chronic exposure to glucocorticoids in response to long-term stress is thought to be a risk factor for major depression. Depression is associated with disturbances in the gut microbiota composition and peripheral and central energy metabolism. However, the relationship between chronic glucocorticoid exposure, the gut microbiota, and brain metabolism remains largely unknown. In this study, we first investigated the effects of chronic corticosterone exposure on various domains of behavior in adult male C57BL/6J mice treated with the glucocorticoid corticosterone to evaluate them as an animal model of depression. We then examined the gut microbial composition and brain and plasma metabolome in corticosterone-treated mice. Chronic corticosterone treatment resulted in reduced locomotor activity, increased anxiety-like and depression-related behaviors, decreased rotarod latency, reduced acoustic startle response, decreased social behavior, working memory deficits, impaired contextual fear memory, and enhanced cued fear memory. Chronic corticosterone treatment also altered the composition of gut microbiota, which has been reported to be associated with depression, such as increased abundance of Bifidobacterium, Turicibacter, and Corynebacterium and decreased abundance of Barnesiella. Metabolomic data revealed that long-term exposure to corticosterone led to a decrease in brain neurotransmitter metabolites, such as serotonin, 5-hydroxyindoleacetic acid, acetylcholine, and gamma-aminobutyric acid, as well as changes in betaine and methionine metabolism, as indicated by decreased levels of adenosine, dimethylglycine, choline, and methionine in the brain. These results indicate that mice treated with corticosterone have good face and construct validity as an animal model for studying anxiety and depression with altered gut microbial composition and brain metabolism, offering new insights into the neurobiological basis of depression arising from gut-brain axis dysfunction caused by prolonged exposure to excessive glucocorticoids.

Sleep oscillations and their relations with sleep-dependent memory consolidation in early course psychosis and first-degree relatives

Sleep spindles mediate sleep-dependent memory consolidation, particularly when coupled to neocortical slow oscillations (SOs). Schizophrenia is characterized by a deficit in sleep spindles that correlates with reduced overnight memory consolidation. Here, we examined sleep spindle activity, SO-spindle coupling, and both motor procedural and verbal declarative memory consolidation in early course, minimally medicated psychosis patients and non-psychotic first-degree relatives. Using a four-night experimental procedure, we observed significant deficits in spindle density and amplitude in patients relative to controls that were driven by individuals with schizophrenia. Schizophrenia patients also showed reduced sleep-dependent consolidation of motor procedural memory, which correlated with lower spindle density. Contrary to expectations, there were no group differences in the consolidation of declarative memory on a word pairs task. Nor did the relatives of patients differ in spindle activity or memory consolidation compared with controls, however increased consistency in the timing of SO-spindle coupling were seen in both patients and relatives. Our results extend prior work by demonstrating correlated deficits in sleep spindles and sleep-dependent motor procedural memory consolidation in early course, minimally medicated patients with schizophrenia, but not in first-degree relatives. This is consistent with other work in suggesting that impaired sleep-dependent memory consolidation has some specificity for schizophrenia and is a core feature rather than reflecting the effects of medication or chronicity.

Cannabis smoke and oral Δ9THC enhance working memory in aged but not young adult subjects.

With increased legalization of recreational and medical cannabis, use of this drug is growing rapidly among older adults. As cannabis use can impair cognition in young adults, it is critically important to understand how consumption interacts with the cognitive profile of aged individuals, who are already at increased risk of decline. The current study was designed to determine how cannabis influences multiple forms of cognition in young adult and aged rats of both sexes when delivered via two translationally-relevant routes of administration. Acute exposure to cannabis smoke enhanced prefrontal cortex-dependent working memory accuracy in aged males, but impaired accuracy in aged females, while having no effects in young adults of either sex. In contrast, the same cannabis smoke exposure regimen had minimal effects on a hippocampus-dependent trial-unique non-matching to location mnemonic task, irrespective of age or sex. In a second set of experiments, chronic oral consumption of Δ9-tetrahydrocannabinol (Δ9THC) enhanced working memory in aged rats of both sexes, while having no effects in young adults. In contrast, the same oral Δ9THC regimen did not affect spatial learning and memory in either age group. Minimal age differences were observed in Δ9THC pharmacokinetics with either route of administration. Together, these results show that cannabis and Δ9THC can attenuate working memory impairments that emerge in aging. While these enhancing effects do not extend to hippocampus-dependent cognition, cannabis does not appear to exacerbate age-associated impairments in this cognitive domain.

Time-restricted feeding prevents memory impairments induced by obesogenic diet consumption, via hippocampal thyroid hormone signaling

ObjectiveThe early consumption of calorie-rich diet disrupts circadian rhythms and has adverse effects on memory, yet the effects of time-restricted feeding (TRF) and the underlying molecular mechanisms are unknown. Here, we set out to identify the behavioral and molecular circadian rhythms disruptions generated by juvenile obesogenic diet consumption and their restoration by TRF in male mice. MethodsMetabolic rhythms were measured by indirect calorimetry and memory performances by behavioral tasks. Hippocampal translatome (pS6_TRAP), enrichment and co-regulated gene network analyses were conducted to identify the molecular pathways involved in memory impairments and their restoration by TRF. Differential exon usage analyses, mass spectrometry and pharmacological intervention were used to confirm thyroid hormone signaling involvement. ResultsWe show that four weeks of TRF restore the rhythmicity of metabolic parameters and prevents memory impairments in mice fed a high fat-high sucrose (HFS) diet since weaning, independently of body fat levels. Hippocampal translatome and differential exon usage analyses indicate that impaired memory of mice under ad libitum HFS diet is accompanied by reduced thyroid hormone signaling and altered expression of astrocytic genes regulating glutamate neurotransmission. TRF restored the diurnal expression variation of part of these genes and intra-hippocampal infusion of T3, the active form of thyroid hormone, rescues memory performances and astrocytic gene expression of ad libitum HFS diet-fed mice. ConclusionsThus, thyroid hormones contribute to the TRF positive effects on both metabolism and memory in mice fed an obesogenic diet, highlighting this nutritional approach as a powerful tool in addressing obesity brain comorbidities and paving the way for further mechanistic studies on hippocampal thyroid signaling.

Anti-Ma-2 associated encephalitis presenting as slowly progressive dementia and cerebellar atrophy

Abstract Cognitive impairment can be a manifestation of a neurodegenerative disease or may have a reversible etiology. Among reversible causes, metabolic, nutritional and autoimmune conditions are commonly evaluated. We report 43-year-old lady who presented with history of personality changes first noted three years back. Subsequently, she developed slowness in speech and activities of her daily living, hypersomnolence, dream enactment, unexplained weight gain and memory impairment. Cognitive assessment revealed poor delayed recall, impaired copying, calculation deficits and bradyphrenia. Mild bradykinesia and rigidity of upper limbs were also noted. MRI brain showed minimal cerebral atrophy and gross cerebellar atrophy. Blood investigation revealed strongly positive anti Ma-2 antibodies. Whole body PET-CT was negative. Ma-2 encephalitis is characterised by diencephalic, brainstem and /or limbic involvement. Presence of Ma-2 antibodies has strong link with malignancies, commonest being the testicular cancer. Anti- neuronal antibodies in association with progressive cognitive impairment in the absence of encephalitis like picture is increasingly being recognized. Although autoimmune work up is generally advocated for rapidly progressive dementia, this case highlights the need to consider antineuronal antibody evaluation in a young individual with longer duration of symptoms.

Differential association between childhood trauma subtypes and neurocognitive performance in adults with major depression

BackgroundNeurocognitive impairment is one of the prominent manifestations of major depressive disorder (MDD). Childhood trauma enhances vulnerability to developing MDD and contributes to neurocognitive dysfunctions. However, the distinct impacts of different types of childhood trauma on neurocognitive processes in MDD remain unclear.MethodsThis study comprised 186 individuals diagnosed with MDD and 268 healthy controls. Childhood trauma was evaluated using the 28-item Childhood Trauma Questionnaire-Short Form. Neurocognitive abilities, encompassing sustained attention, vigilance, visual memory, and executive functioning, were measured by the Cambridge Neuropsychological Testing Automated Battery.ResultsMultivariable linear regressions revealed that childhood trauma and MDD diagnosis were independently associated with neurocognitive impairment. Physical neglect was associated with impaired visual memory and working memory. MDD diagnosis is associated with working memory and planning. Interactive analysis revealed that physical/sexual abuse was associated with a high level of vigilance and that emotional neglect was linked with better performance on cognitive flexibility in MDD patients. Furthermore, childhood emotional abuse, physical abuse, and emotional neglect were revealed to be risk factors for developing early-onset, chronic depressive episodes.ConclusionThus, specific associations between various childhood traumas and cognitive development in depression are complex phenomena that need further study.

<i>Kalayanaka Ghrita</i> Ameliorates Okadaic Acid Induced Memory Deficits in Wistar Rats

Background: Alzheimer’s disease depicts the characteristic features of intracellular neurofibrillary tangles and extracellular amyloid plaques. Kalyanaka ghrita (KG) is an Ayurvedic formulation used to treat impaired learning and memory such as Manasmandata or Buddhimandyata. KG is traditionally used to enhance memory. The constituents present in KG are also reported to be memory-enhancing, anti-inflammatory, and antioxidant and KG is reported to be effective in neurodegeneration in rats induced by β-amyloid. Aim: This study is aimed to validate the effect of KG on memory deficit, tauopathy and neurodegeneration induced by intracerebroventricular administration of okadaic acid. Methods: Okadaic acid was administered intracerebroventricularly on day 7 to the Wistar rats. KG was administered orally or intranasal from day 14 to 35 to the respective groups. The behavioural parameters on spatial memory, social recognition, and novel object recognition tests were determined. The molecular parameters such as brain acetylcholinesterase activity, protein phosphatase 2A, antioxidant parameters, monoamine levels and the brain histopathology were studied. Results: KG treatment significantly improved cognition, as evidenced by a decrease in escape latency, path length, and social and novel object recognition tests. KG treatment also increased the brain Protein phosphatase 2A, reversed the oxidative stress, and decreased brain acetylcholinesterase. The brain monoamines were reversed upon treatment with KG. Further, the molecular and histological studies confirmed the prevention of neuronal damage. Conclusion: These findings imply the traditional nootropic property of KG. The neuroprotective properties and decreased neurofibrillary tangles upon treatment with KG suggest KG to be a potential therapy for AD-like neurodegeneration.

KAMPO SI-SHEN EXTRACT PREVENTS LPS-INDUCED WORKING MEMORY IMPAIRMENT AND DEPRESSIVE BEHAVIOR IN MICE

Si-Shen decoction is a mild medicinal dietary material composed of lotus seeds, gorgon, poria and yam. In vitro studies have proved the biological activity of four individual medicinal materials, but the effects of the combination prescription have yet to be evaluated in vivo in the past. This study prepared the Si-Shen extracts (SSE) by heating reflux with 50% alcohol. The prepared extracts contained functional components, including [Formula: see text][Formula: see text]mg of QE/g of flavonoids and [Formula: see text][Formula: see text]mg of GAE/g of polyphenols. The antioxidant activity of SSE was verified by the DPPH and FRAP assays. Moreover, the prepared SSE is not cytotoxic below the concentration of 2[Formula: see text]mg/mL according to the ISO10993-5 test method. Feeding the SSE for 28 days is sufficient to prevent lipopolysaccharide (LPS)-induced spatial memory impairment and anxiety symptoms, and SSE improves physical fitness. Further experiments demonstrated that SSE elevated the level of acetylcholine in the brain and serum superoxide dismutase activity. This research demonstrated the apparent efficacy and safety of the SSE, which will be further developed into innovative health products related to disease prevention.

Perinatal exposure to PBDE-47 decreases brain glucose metabolism in male adult rats: Associations with shifts in triiodothyronine and neurobehavior

BackgroundThe brominated flame retardant 2, 2′, 4, 4′-tetrabromodiphenyl ether (PBDE-47) is well known as a developmental neurotoxicant, yet the underlying mechanisms remain elusive. Increasing evidence has demonstrated that brain glucose metabolism perturbation plays a role in neural impairments. Nevertheless, whether this disturbance is involved in PBDE-47-induced neurotoxicity remains unknown. ObjectivesTo explore the impacts of perinatal PBDE-47 exposure on brain glucose metabolism, and its link to thyroid hormones (THs) levels as well as neurobehavioral changes. MethodsFemale Sprague-Dawley rats were orally exposed to PBDE-47 at environmentally relevant levels (0.1, 1.0, and 10.0 mg/kg bw) from pre-pregnancy through weaning of offspring. The male offspring were continued to raise to 88 days after birth for follow-up experiments. Morris water maze and Open field tests were performed to assess the neurobehavioral alterations. The brain glucose metabolism was evaluated using 18F-labeled fluorodeoxyglucose (18F-FDG) positron emission tomography. Serum THs levels were measured via enzyme-linked immunosorbent assay. ResultsPerinatal exposure to PBDE-47 induced neurobehavioral impairments in adult male rats as evidenced by learning and memory impairments, hyperactivity and anxiety-like behavior. Moreover, positron emission tomography showed that the glucose metabolism in the whole and the specific brain regions were markedly declined. Interestingly, variations in brain glucose metabolism were associated with the increased serum triiodothyronine (T3) levels, and both were linked to neurobehavioral disorders. ConclusionExposure to environmentally related levels of PBDE-47 at critical developmental stages lowers glucose metabolism in the whole brain and in various brain regions, which is associated with behavioral and cognitive deficits in adult male rats. Moreover, the association may be influenced by the disturbance of T3 homeostasis.

Trans-cinnamaldehyde attenuates neuronal cytotoxicity and memory impairment in comorbid exposure to sleep-deprivation and formalin inhalation in rat model

BackgroundSynapse impairment is associated with decline in learning ability and memory loss, which can be activated by enhanced oxidative stress, inflammation and hypermyelination of neurons in the prefrontal cortex (PFC), hippocampus (Hipp), and other brain regions. Thus, we examined trans-cinnamaldehyde (TCA) neuroprotective mechanisms in cortico-hippocampal axis of rat deprived of sleep with concomitant long-time exposure to formalin inhalation.MethodsThirty-six (36) healthy male Wistar rats (average of 170 ± 10 g) were randomly assigned into six experimental groups (n = 6). Positive control group (CON), TCA (40 mg/kg bw) control group (TCA), sleep deprivation exposure group (SD), 20% formalin inhalation group (FEx), SD + FEx group (SD + FEx) and SD + FEx + TCA group (SD + FEx + TCA). 20% formalin exposure was done via inhalation, with sleep deprivation for 8 h a day, 5 days/week, from day 1 to 56 while TCA was given intraperitoneally, from day 28 to 56 and thereafter, behavioral, biochemical, immunohistochemistry and histomorphology was assessed.ResultsSD, FEx and SD + FEx exposure provokes loss of body weight across days, impair short- and long-term memory functions and heightened pro-oxidants molecules with marked decreased endogenous antioxidants status in cortico-hippocampal brain region of the animal. The degree of cortico-hippocampal proinflammatory mediators were further upregulated supported with loss of pyramidal neurons, severe white matter degeneration, axonal loss and hypermyelination. In addition, SD + FEx exposure exacerbates cortico-hippocampal Nrf2 immunopositive cells. Herein, all these assaults were mitigated by TCA treatment, due to its ability to modulate Nrf2 protein, oxido-inflammatory signaling molecule and restore cortico-hippocampal neurons.ConclusionTaken together, our findings showed the positive neuroprotective effects of TCA against neurodegeneration associated with SD + FEx exposure, by reducing oxido-inflammatory molecules, increasing the endogenous antioxidant defense system modulating Nrf2 protein and abating the loss of cortico-hippocampal neurons and histoarchitecture.Graphical

Acute depletion of complement C3 with cobra venom factor attenuates memory deficits induced by status epilepticus.

Status epilepticus (SE) significantly increases the risk for the development of unprovoked seizures, memory loss, and temporal lobe epilepsy. Our prior studies showed that SE increases complement C3 signaling in the hippocampus, which parallels memory deficits. Additionally, C3 knockout (KO) mice were protected against SE-induced memory impairments, suggesting a mechanistic role for C3 in this pathophysiology. In this study, we utilized cobra venom factor (CVF), a structural analog of C3 that results in its depletion, to investigate the protective effects of post-SE C3 ablation on memory deficits that develop during epileptogenesis. SE was induced in male rats using the chemoconvulsant pilocarpine. Two weeks later, control (C) and SE rats were treated with either vehicle (V) or CVF. Recognition memory was assessed using the novel object recognition (NOR) test in four groups (C + V, C + CVF, SE + V, and SE + CVF). Immunoblotting was used to measure hippocampal protein levels of C3 along with synaptic, astrocyte, and blood-brain barrier (BBB) stability markers, Psd95, GFAP, and albumin, respectively. In the NOR test, rats in the C + V and C + CVF groups spent more time exploring the novel object. SE + V rats explored both objects equally, while SE + CVF rats spent significantly more on the novel object, suggesting a rescue of cognitive performance by CVF. While CVF-mediated C3 depletion did not restore normal protein levels of Psd95 or GFAP in hippocampi of SE + CVF rats, CVF treatment attenuated SE-induced extravasation of albumin, suggesting potential rescue of BBB stability. Our findings indicate that acute C3 depletion with CVF can attenuate memory deficits that develop during SE-induced epileptogenesis. This finding further suggests that targeting C3 could hold promise in addressing cognitive comorbidities associated with SE and acquired epilepsy. A long-lasting seizure, known as status epilepticus (SE), can raise the chance of having more seizures in the future and can lead to memory problems. While the exact reasons for these issues are not completely known, it is believed that brain inflammation might be involved. In this study, we show that the activation of the body's immune response, especially a part called the C3 component, plays a role in the memory problems that occur after an episode of SE.

Corticonigral projections recruit substantia nigra pars lateralis dopaminergic neurons for auditory threat memories.

Dopaminergic neurons (DANs) in the lateral substantia nigra project to the tail of striatum (TS), which is involved in threat conditioning. Auditory cortex also contributes to threatening behaviors, but whether it directly interacts with midbrain DANs and how these interactions might influence threat conditioning remain unclear. Here, functional mapping revealed robust excitatory input from auditory and temporal association cortexes to substantia nigra pars lateralis (SNL) DANs, but not to pars compacta (SNc) DANs. SNL DANs exhibited unique firing patterns, with irregular pacemaking and higher maximal firing, reflecting different channel complements than SNc DANs. Behaviorally, inhibiting cortex to SNL projections impaired memory retrieval during auditory threat conditioning. Thus, we demonstrate robust corticonigral projections to SNL DANs, contrasting with previous observations of sparse cortical input to substantia nigra DANs. These findings distinguish SNL DANs from other nigral populations, highlighting their role in threatening behaviors and expanding knowledge of cortex to midbrain interactions.

The role of vitamin D: a promising pathway to combat neuropsychiatric lupus disorders.

To evaluate neuropsychiatric manifestations in the pristane-induced lupus (PIL) model, as well as to evaluate immunoregulatory effects of vitamin D (vit-D) in the brain of mice with PIL. Eighty female BALB/c mice were divided into six groups with 90 (3 months) and 180 (6 months) days of experimentation: CO3, CO6 (controls), PIL3, PIL6 (pristane-induced lupus), VD3 and VD6 (PIL supplemented with 1,25-dihydroxyvitamin D). Forced-swim, elevated plus maze and Barnes maze were the behavioral tests performed. Expression of pVDR was assessed by immunofluorescence. Brain IgM and IgG deposits were evaluated by double staining fluorescence. Serum IL-6 and IFN-α1 were quantified by ELISA. AUC-ROC curve was also performed for immunoglobulins. PIL and VD showed depressive-like behavior in the forced-swim test and anxious-like behavior in the elevated plus maze test. PIL also presented cognitive and memory impairment in the Barnes maze test. Additionally, PIL and VD presented higher levels of serum IFN-α1, but not IL-6. Mice supplemented with vit-D had reduced IgM and IgG deposits and increased pVDR expression in the brain after 180 days. The AUC-ROC curve demonstrated high sensitivity and specificity for IgM and IgG in the brain. We observed neuropsychiatric manifestations in this model of systemic lupus erythematosus (SLE), strongly corroborating to PIL model being suitable as a neuropsychiatric lupus (NPSLE) model. Vit-D was able to reduce immunoglobulin deposits in the brain and influenced the levels of serum IL-6 in the animals assessed. Also, it improved memory, but it had no effect on depressive and anxious-like behavior.

Ameliorating Effects of Honey on Ethanol, Caffeine, Morphine and Scopolamine- Novelty Induced Behaviors and Memory Impairment in Male Albino Mice

Ameliorating Effects of Honey on Ethanol, Caffeine, Morphine and Scopolamine- Novelty Induced Behaviors and Memory Impairment in Male Albino Mice