Recognition Test Research Articles

Automated analysis of a novel object recognition test in mice using image processing and machine learning

The novel object recognition test (NORT) is one of the most commonly employed behavioral tests in experimental animals designed to evaluate an animal's interest in and recognition of novelty. However, manual procedures, which rely on researchers’ observations, prevent high throughput analysis. In this study, we developed an automated analysis method for NORT utilizing machine learning-assisted exploratory behavior detection. We recorded the exploratory behavior of the mice using a video camera. The coordinates of the mouse nose and tail base in recorded video files were detected using a pre-trained machine learning model, DeepLabCut. Each video was then segmented into frame images, which were categorized into "exploratory,” or "non-exploratory" frames based on manual observation. Mouse feature vectors were calculated as vectors from the nose to the vertices of the object and were utilized for SVM training. The trained SVM effectively detected exploratory behaviors, showing a strong correlation with human observer assessments. Upon application to NORT, the duration of mouse exploratory behavior towards objects predicted by the SVM exhibited a significant correlation with the assessments made by human observers. The novelty discrimination index derived from the SVM predictions also aligned well with that from human observations.

The effect of cerebellar lesıons on language in Turkısh speakıng indıvıduals

ABSTRACT Background The cerebellum is approximately 10% of the brain volume and is responsible for attention, language, emotion and cognitive functions. Linguistic processing difficulties and cognitive impairments may be observed in individuals with cerebellar lesions depending on the location and severity of the damage. There is no study evaluating language in Turkish-speaking individuals with cerebellar lesions. Objective To determine the differences in linguistic and visuospatial skills of Turkish speaking individuals with cerebellar lesions compared to control groups, including a right hemisphere lesion group and a healthy control group. Method Fifteen patients with cerebellar lesion (without hemispatial neglect and dysarthria), 15 patients with right hemisphere lesion due to right arter cerebri media (without hemispatial neglect) and 15 healthy control were included. To clarify the language impairment specific to cerebellar lesions, we also included individuals with right hemisphere lesions, which are typically assumed not to present with aphasia. The Language Assessment Test for Aphasia (ADD), Benton Judgment of Line Orientation Test, Benton Facial Recognition Test, Single Letter Deletion Test were used. The “Accident Scene” picture was used for collecting narrative speech samples. After a three group comparison a post-hoc pairwise analysis was performed. Results Among the microstructural parameters in the narrative language analysis, the effort ratio was significantly higher in the cerebellar lesion group compared to the healthy control group. Among the non-verbal cognitive tests, the Benton Facial Recognition Test score was significantly lower in the cerebellar and right hemisphere lesion group compared to the healthy control group. Total score, naming and grammar scores in the ADD test were significantly lower in the cerebellar lesion group compared with the healthy control group. There was no difference between cerebellar and right hemisphere lesions in terms of ADD score, ADD subtests and narrative parameters. Conclusion In Turkish-speaking individuals with cerebellar lesions, verbal productivity may be interrupted by effort behaviours, and standard aphasia assessment tests may reveal impaired grammar and naming performance without a diagnosis of aphasia. In addition to reduced efficiency in verbal production, facial recognition may be impaired. We found no difference between individuals with lesions in the cerebellum and right hemisphere. This suggests that ischemic damage may affect different components of language independently of the diagnosis of aphasia.

Risperidone accelerates bone loss in mice models of schizophrenia by inhibiting osteoblast autophagy

BackgroundRisperidone (RIS) is the first-line drug in the clinical treatment of schizophrenia, and long-term use may lead to bone loss and even osteoporosis. This study investigated whether the mechanism of RIS-induced bone loss is related to autophagy. MethodsThe schizophrenia mice were established with the administration of MK-801. Then, RIS were injected, or autophagy inducer rapamycin (RAPA) co-injected for 8 weeks. Cognitive performance was determined by the novel object recognition and Open field tests. Bone loss of schizophrenia mice were assessed using microCT, H&E staining, ALP staining, ARS staining and WB, respectively. Autophagy of schizophrenia mice were detected by immunofluorescence, transmission electron microscopy (TEM) and WB, respectively. In addition, osteogenic differentiation of MC3T3-E1 and BMSCs cells were assessed using H&E staining, ALP staining, ARS staining and WB, respectively. ResultsIn the present study, we found that RIS treatment can promote bone loss in schizophrenia mice and inhibit osteogenic differentiation of MC3T3-E1 and BMSCs cells. Interesting, the number of autophagosome and autophagy-related protein expression were decreased after RIS treatment. However, the bone loss and inhibition of osteogenic differentiation induced by RIS in schizophrenia mice were reversed by autophagy inducer RAPA. ConclusionRIS significantly increased bone loss and inhibited osteogenic differentiation in schizophrenia mice; the underlying mechanism entails suppressing osteoblast autophagy.

Thymoquinone ameliorate oxidative stress, GABAergic neuronal depletion and memory impairment through Nrf2/ARE signaling pathway in the dentate gyrus following cypermethrin administration

BackgroundExposure to chemical toxins, including insecticides, harms bodily organs like the brain. This study examined the neuroprotective of thymoquinone on the cypermethrin’s harmful effects on the histoarchitecture of the dentate gyrus and motor deficit in the dentate gyrus.MethodsForty adult male rats (180–200 g) were randomly divided into 5 groups (n = 8 per group). Groups I, II, III, IV, and V received oral administration of 0.5 ml of phosphate-buffered saline, cypermethrin (20 mg/kg), thymoquinone (10 mg/kg), cypermethrin (20 mg/kg) + thymoquinone (5 mg/kg), and cypermethrin (20 mg/kg) + thymoquinone (10 mg/kg) for 14 days respectively. The novel object recognition test that assesses intermediate-term memory was done on days 14 and 21 of the experiment. At the end of these treatments, the animals were euthanized and taken for cytoarchitectural (hematoxylin and eosin; Cresyl violet) and immunohistochemical studies (Nuclear factor erythroid 2-related factor 2 (Nrf2), Parvalbumin, and B-cell lymphoma 2 (Bcl2).ResultThe study shows that thymoquinone at 5 and 10 mg/kg improved Novelty preference and discrimination index. Thymoquinone enhanced Nissl body integrity, increased GABBAergic interneuron expression, nuclear factor erythroid 2-derived factor 2, and enhanced Bcl-2 expression in the dentate gyrus. It also improved the concentration of nuclear factor erythroid 2-derived factor 2, increased the activities of superoxide dismutase and glutathione, and decreased the concentration of malondialdehyde level against cypermethrin-induced neurotoxicity.Conclusionthymoquinone could be a therapeutic agent against cypermethrin poisoning.

Peripherally-restricted recurrent infection by engineered E. coli strain modulates hippocampal proteome promoting memory impairments in a rat model

Commensal bacteria that breach endothelial barrier has been reported to induce low grade chronic inflammation producing disease symptoms in major peripheral tissues. In this study, we investigated the role of genetically modified cellular invasive form of commensal E. coli K12 (SK3842) in cognitive impairment. Low-grade systemic infection model was developed using recurring peripheral inoculation of live bacteria in Wistar rats. To examine memory parameters, Novel object recognition test and Radial arm maze test were performed. Differential protein expression profiling of rat hippocampus was carried out using LC-MS/MS and subsequently quantified using SWATH. HBA1/2, NEFH, PFN1 and ATP5d were chosen for validation using quantitative RT-PCR. Results showed drastic decline in Recognition memory of the SK3842 infected rats. Reference and Working Memory of the infected group were also significantly reduced in comparison to control group. Proteome analysis using LC-MS/MS coupled with SWATH revealed differential expression of key proteins that are crucial for the maintenance of various neurological functions. Moreover, expression of NEFH and PFN1transcripts were found to be in line with the proteomics data. Protein interaction network of these validated proteins generated by STRING database converged to RhoA protein. Thus, the present study establishes an association between peripheral infection of a hippocampal protein network dysregulation and overall memory decline.

Prior familiarity enhances recognition memory of faces, not just images of faces, when accompanied by conceptual information.

A recent paper reported that recognition discriminability was improved for faces that were familiarized prior to study, but only if that familiarization protocol included conceptual information, like a name (Akan & Benjamin, Journal of Memory and Language,131, 104,433, 2023). In those experiments, familiarity with each facial identity was gained through exposures to the same facial image prior to study, and memory for each facial identity was tested using the same images across study and test. That design characteristic has a serious constraint on generality, since it is possible that prior conceptual information enhances memory for images (of faces), but not for the representation of the face itself. Here we evaluated whether this finding generalizes to a paradigm in which each exposure of a face is a novel image. In two experiments, faces were familiarized with orienting tasks that induced more perceptual or more conceptual processing prior to study and test phases. Results from recognition tests replicated the results from Akan and Benjamin (2023): (1) Discriminability was enhanced when prior familiarity involved conceptual processing but not when it involved perceptual processing, and (2) familiarity gained through either perceptual or conceptual processing led to an increase in both correct and false identifications. This successful replication in a design with exclusively novel images indicates that the discriminability advantage provided by conceptual familiarity goes beyond memory for facial images and applies to memory for faces. These findings have implications in practical contexts, such as eyewitness identification situations involving suspects who are previously known or familiar to the witness.

Repetition dynamically and rapidly increases cortical, but not hippocampal, offline reactivation

No sooner is an experience over than its neural representation begins to be transformed through memory reactivation during offline periods. The lion's share of prior research has focused on understanding offline reactivation within the hippocampus. However, it is hypothesized that consolidation processes involve offline reactivation in cortical regions as well as coordinated reactivation in the hippocampus and cortex. Using fMRI, we presented novel and repeated paired associates to participants during encoding and measured offline memory reactivation for those events during an immediate post-encoding rest period. post-encoding reactivation frequency of repeated and once-presented events did not differ in the hippocampus. However, offline reactivation in widespread cortical regions and hippocampal-cortical coordinated reactivation were significantly enhanced for repeated events. These results provide evidence that repetition might facilitate the distribution of memory representations across cortical networks, a hallmark of systems-level consolidation. Interestingly, we found that offline reactivation frequency in both hippocampus and cortex explained variance in behavioral success on an immediate associative recognition test for the once-presented information, potentially indicating a role of offline reactivation in maintaining these novel, weaker, memories. Together, our findings highlight that endogenous offline reactivation can be robustly and significantly modulated by study repetition.

Personality may modulate learning and memory differences in two taxa of the African striped mouse genus Rhabdomys

AbstractDifferent environments place different cognitive demands on constituent taxa. Learning and memory involve cognitive processes with associated costs, and it is expected that different levels of learning will occur in taxa from different environments. Greater memory loads linked to increased environmental complexity require greater learning and memory capacities. We investigated the variation in learning and memory in sister taxa of striped mice (genus Rhabdomys). We studied two populations each of the mesic grassland‐occurring R. d. chakae and the mostly arid‐occurring R. pumilio. We conducted two sets of experiments. (1) In a novel object recognition (NOR) test, we assessed memory by recording the duration of exploration of similar and novel objects by test mice. (2) In an associative learning task, we assessed whether mice could associate specific scents with or without a food incentive or with different quantities of the food incentive in previous training phases. We measured the latency of mice to contact scents in a two‐sample choice in the test phase. In the NOR test, R. pumilio spent less time investigating similar objects in a training trial than R. d. chakae but increased absolute exploration of the novel object when presented with a novel and a familiar object in the retention trial, suggesting a sensitization to the novel object by R. pumilio. In the associative learning experiments, R. pumilio approached the stimuli faster than R. d. chakae, whereas mice from both taxa preferred scents associated with a seed versus no seed and scents associated with 5 seeds versus 1 seed. The data provide evidence of taxon‐level differences in learning and memory, likely related to environmentally modulated personality differences between the taxa.

Remimazolam attenuates lipopolysaccharide-induced neuroinflammation and cognitive dysfunction

ObjectiveRemimazolam, a novel benzodiazepine, is widely used as an anesthetic in endoscopic procedures; however, its effects on cognitive function remain unclear, limiting its broader application in general anaesthesia. Neuroinflammation is a well-established key factor in the etiology and progression of cognitive dysfunction, including conditions such as Alzheimer's disease, Parkinson's disease, postoperative delirium, and postoperative cognitive dysfunction. Preclinical studies have demonstrated that remimazolam exerts anti-inflammatory and neuroprotective effects, and clinical reports indicate a reduced incidence of postoperative delirium in patients treated with remimazolam. Nevertheless, whether remimazolam improves cognitive function through its anti-inflammatory properties remains uncertain. This study aimed to investigate the neuroprotective effects of remimazolam and its underlying mechanism in a lipopolysaccharide (LPS)-induced model of neuroinflammation, neuronal injury, and cognitive dysfunction MethodsC57BL/6 J male mice were administered LPS intraperitoneally to establish a model of neuroinflammation-induced cognitive impairment. A subset of mice received remimazolam via intraperitoneal injection 30 minutes prior to LPS administration. Cognitive performance was evaluated using behavioural tests, including the Morris Water Maze (MWM), Novel Object Recognition (NOR) test, and Open Field Test (OFT). Hippocampal tissues were analyzed by haematoxylin-eosin (HE) staining to assess structural changes. Inflammatory markers, including Interleukin (IL)-6, IL-1β, and tumor necrosis factor-α, were quantified using enzyme-linked immunosorbent assay (ELISA) and real-time quantitative PCR. Immunofluorescence was used to detect translocator protein (TSPO) and markers of microglia activation (IBA-1, CD16/32, and CD206). Results(1) Remimazolam reversed LPS-induced cognitive deficits, as evidenced by shorter spatial exploration latency and increased platform crossings in the MWM, and an elevated recognition index in the NOR test. (2) Remimazolam improved hippocampal morphology, reducing LPS-induced neuronal damage. (3) Remimazolam significantly decreased levels of hippocampal inflammatory cytokines, inhibited microglial activation, promoted M2-type microglia polarization, and increased TSPO expression. ConclusionRemimazolam demonstrated neuroprotective and anti-neuroinflammatory effects in a mouse model of LPS-induced cognitive impairment. These effects are likely mediated through the regulation of TSPO, which inhibits microglial activation and promotes the polarization of microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype.

Machine Learning-Assisted Gesture Sensor Made with Graphene/Carbon Nanotubes for Sign Language Recognition.

Gesture sensors are essential to collect human movements for human-computer interfaces, but their application is normally hampered by the difficulties in achieving high sensitivity and an ultrawide response range simultaneously. In this article, inspired by the spider silk structure in nature, a novel gesture sensor with a core-shell structure is proposed. The sensor offers a high gauge factor of up to 340 and a wide response range of 60%. Moreover, the sensor combining with a deep learning technique creates a system for precise gesture recognition. The system demonstrated an impressive 99% accuracy in single gesture recognition tests. Meanwhile, by using the sliding window technology and large language model, a high performance of 97% accuracy is achieved in continuous sentence recognition. In summary, the proposed high-performance sensor significantly improves the sensitivity and response range of the gesture recognition sensor. Meanwhile, the neural network technology is combined to further improve the way of daily communication by sign language users.

GnRH protective effects against long-term potentiation impairment induced by AANAT-siRNA

There is an interplay between the gonadotropin-releasing hormone (GnRH) and melatoninergic systems. The key enzyme of melatonin synthesis (arylalkylamine N-acetyltransferase, AANAT), and GnRH receptors are expressed in the hippocampus. While it has been shown that hippocampal AANAT enzyme activity is necessary for proper hippocampal cognitive function, their role in long-term potentiation (LTP) induction is not fully understood. In current study, the impact of GnRH on LTP induction was investigated, while hippocampal melatonin synthesis had been inhibited. The melatonin synthesis was inhibited by AANAT-siRNA administration, and LTP was induced using in vivo field potential electrophysiological recording.Animals were divided into 5 groups: Intact, vehicle, siRNA, GnRH and siRNA+GnRH. All animals, except intact group, experienced the stereotaxic surgery and intra-hippocampal cannulation to receive vehicle agent, AANAT siRNA (0.5 μg/hip), GnRH (1 ng/rat), and AANAT siRNA+GnRH. The recognition memory was assessed by Novel object recognition test. The field potential electrophysiology experiment was conducted by stimulating the Schaffer collateral pathway, and LTP induction was carried out through high-frequency stimulation (HFS). After recording, animals' brain was isolated and quickly frozen for further hippocampal melatonin levels measurement by LC-MS and AANAT mRNA levels by qRT-PCR.GnRH injection in the hippocampus increased local AANAT-mRNA expression and melatonin levels. GnRH-treated animals displayed higher LTP amplitude compared to intact, vehicle and siRNA groups. While the reduction in hippocampal melatonin levels by AANAT-siRNA inhibited LTP and impaired recognition memory, the GnRH prevented these adverse effects. The data suggests that GnRH have protective effects against AANAT-siRNA-induced LTP decline. The protective mechanism at least partially, may be related to the increased expression of local AANAT-mRNA.

A new test for evaluation of marginal cognitive function deficits in idiopathic normal pressure hydrocephalus through expressing texture recognition by sound symbolic words.

The number of dementia patients is increasing with population aging. Preclinical detection of dementia in patients is essential for access to adequate treatment. In previous studies, dementia patients showed texture recognition difficulties. Onomatopoeia or sound symbolic words (SSW) are intuitively associated with texture impressions and are less likely to be affected by aphasia and description of material perception can be easily obtained. In this study, we aimed to create a test of texture recognition ability expressed by SSW to detect the presence of mild cognitive disorders. The sound symbolic words texture recognition test (SSWTRT) is constructed from 12 close-up photos of various materials and participants were to choose the best SSW out of 8 choices to describe surface texture in the images in Japanese. All 102 participants seen in Juntendo University Hospital from January to August 2023 had a diagnosis of possible iNPH (age mean 77.9, SD 6.7). The answers were scored on a comprehensive scale of 0 to 1. Neuropsychological assessments included MMSE, FAB, and the Rey Auditory Verbal Learning Test (RAVLT), Pegboard Test, and Stroop Test from the EU-iNPH Grading Scale (GS). In study 1 the correlation between SSWTRT and the neuropsychological tests were analyzed. In study 2, participants were divided into two groups: the Normal Cognition group (Group A, n = 37) with MMSE scores of 28 points or above, and the Mild Cognitive Impairment group (Group B, n = 50) with scores ranging from 22 to 27 points, and its predictability were analyzed. In study 1, the total SSWTRT score had a moderate correlation with the neuropsychological test results. In study 2, there were significant differences in the SSWTRT scores between groups A and B. ROC analysis results showed that the SSWTR test was able to predict the difference between the normal and mildly impaired cognition groups. The developed SSWTRT reflects the assessment results of neuropsychological tests in cognitive deterioration and was able to detect early cognitive deficits. This test not only relates to visual perception but is likely to have an association with verbal fluency and memory ability, which are frontal lobe functions.

Activation of D2-like dopamine receptors improves the neuronal network and cognitive function of PPT1KI mice.

Palmitoyl-protein thioesterase 1 (PPT1) is a lysosomal depalmitoylation enzyme that mediates protein posttranslational modifications. Loss-of-function mutation of PPT1 causes a failure of the lysosomal degradation of palmitoylated proteins and results in a congenital disease characterized by progressive neuronal degeneration referred to as infantile neuronal ceroid lipofuscinosis (INCL). A mouse knock-in model of PPT1 (PPT1-KI) was established by introducing the R151X mutation into exon 5 of the PPT1 gene, which exhibited INCL-like pathological lesions. We previously reported that hippocampal γ oscillations were impaired in PPT1 mice. Hippocampal γ oscillations can be enhanced by selective activation of the dopamine D4 receptor (DR4), a dopamine D2-like receptor. In this study, we investigated the changes in DR expression and the effects of dopamine and various DR agonists on neural network activity, cognition and motor function in PPT1KI mice. Cognition and motor defects were evaluated via Y-maze, novel object recognition and rotarod tests. Extracellular field potentials were elicited in hippocampal slices, and neuronal network oscillations in the gamma frequency band (γ oscillations) were induced by perfusion with kainic acid (200 nM). PPT1KI mice displayed progressive impairments in γ oscillations and hippocampus-related memory, as well as abnormal expression profiles of dopamine receptors with preserved expression of DR1 and 3, increased membrane expression of DR4 and decreased DR2 levels. The immunocytochemistry analysis revealed the colocalization of PPT1 with DR4 or DR2 in the soma and large dendrites of both WT and PPT1KI mice. Immunoprecipitation confirmed the interaction between PPT1 and DR4 or DR2. The impaired γ oscillations and cognitive functions were largely restored by the application of exogenous dopamine, the selective DR2 agonist quinpirole or the DR4 agonist A412997. Furthermore, the administration of A412997 (0.5 mg/kg, i.p.) significantly upregulated the activity of CaMKII in the hippocampus of 5-month-old PPT1KI mice. Collectively, these results suggest that the activation of D2-like dopamine receptors improves cognition and network activity in PPT1KI mice and that specific DR subunits may be potential targets for the intervention of neurodegenerative disorders, such as INCL.

Therapeutic effects of alpha lipoic acid and/or caffeine-loaded chitosan nanoparticles on memory impairment and neurochemical changes in high-fat diet-induced obese rats

The therapeutic effects of alpha lipoic acid (LA) and/or caffeine-loaded chitosan nanoparticles (CCNPs) on obesity-induced memory impairment were evaluated in the present study. Rats were divided into control rats, obese rats induced by high fat diet (HFD) and obese rats treated with LA and/or CCNPs. Obesity was confirmed by measuring the body mass index (BMI). Memory and cognitive functions were evaluated by novel object recognition test (NORT). The levels of serotonin (5-HT), dopamine (DA), norepinephrine (NE), lipid peroxidation (MDA), nitric oxide (NO), reduced glutathione (GSH), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), leptin (LEP) and ghrelin (GHR) and the activities of monoamine oxidase (MAO), acetylcholinesterase (AchE) and Na+,K+,ATPase were determined in the cortex and hippocampus. The cerebral histopathological alterations were examined in obese rats.Obese rats showed impaired memory and exhibited significant neurochemical changes, including decreased levels of 5-HT, DA, GSH, GHR, and Na+,K+-ATPase activity, as well as an increase in AchE, MAO, MDA, NO, IL-1β, TNF-α, and LEP. LA and/or CCNPs treatment reduced BMI and improved memory. LA or CCNPs alleviated the cortical and hippocampal neurochemical changes and histopathological changes induced by obesity. Furthermore, LA and CCNPs exhibited antioxidant and anti-inflammatory properties, which likely contributed to their effects. However, no synergistic effect was observed between LA and CCNPs. These findings suggest that LA or CCNPs may be a potential therapy against obesity and its adverse effects on memory, mediated by their ability to restore monoamine levels and exhibit antioxidant and anti-inflammatory properties.

Remote assessment of music perception in pediatric cochlear implant recipients

Objective The primary objective of this study was to explore the feasibility of remotely assessing music perception in paediatric cochlear implant (CI) recipients. Pitch direction discrimination (PDD) and timbre recognition (TR) tests were administered remotely. We aimed to provide insights into the potential benefits and challenges of remote assessments. Design The study was exploratory in nature. All participants underwent remote assessments for the PDD and TR tests. Eight participants completed both online and face-to-face tests. Supervising parents in remote tests completed the System Usability Scale (SUS). Study Sample A cohort of 27 children with CI, averaging 11.19 years of age, participated in this study. Results In the online condition, the average PDD score was 3.29 semitones (st), the TR score was 37.86%, and the average duration for PDD and TR testing was 9.98 and 6.18 minutes, respectively. Face-to-face sessions had an average PDD score of 3.00 st, a TR score of 32.81% and durations of 10.20 and 5.42 minutes for PDD and TR tests, respectively. The SUS score averaged 64.04. Conclusion These findings contribute to the growing body of knowledge supporting the integration of remote assessments in audiological practices.

Emotional false memories: the impact of response bias under speeded retrieval conditions

ABSTRACT Emotional false memory findings using the DRM paradigm have been marked by higher false alarms to negatively arousing compared to neutral critical lure items. Explanations for these findings have mainly focused on false memory-based accounts. However, here we address the question of whether a response bias for emotional stimuli can, at least in part, explain this phenomenon. Participants viewed both neutral and negative arousing DRM lists and completed a recognition test in speeded or self-paced conditions. Speeded test reduces the opportunity to adjust response bias. Analysis showed no significant difference in false recognition across critical lure types for the speeded condition, but false recognition was higher for negative compared to neutral critical lures in the self-paced condition. We argue that when retrieval does not allow for shifts in response criteria, false alarms to negative emotional critical lures appear more similar to neutral equivalents. The discussion explores memory-based and criterion-shift explanations for the enhanced emotional false memory finding.

Fingolimod alleviates type 2 diabetes associated cognitive decline by regulating autophagy and neuronal apoptosis via AMPK/mTOR pathway

This study aimed to reveal the role of fingolimod (FTY720) in mice with type 2 diabetes-associated cognitive decline and explore its potential neuroprotective mechanism. Mice were divided into five groups: normal control, normal control + FTY720 (1.0 mg/kg/day), type 2 diabetes mellitus, type 2 diabetes mellitus + low-dose FTY720 (0.5 mg/kg/day), and type 2 diabetes mellitus + high-dose FTY720 (1.0 mg/kg/day). Different doses of FTY720 were administered daily for 8 weeks after the induction of type 2 diabetes using a four-week high-fat diet feeding combined with continuous low-dose intraperitoneal injections of streptozotocin. After 8 weeks of treatment, the body weights and fasting blood glucose levels of mice from the five groups were compared. Morris water maze and new object recognition tests were used to evaluate cognitive function. Pathological changes in the hippocampal CA1 region were observed using haematoxylin-eosin and Nissl staining, and the ultrastructure of the hippocampal neurones was assessed using transmission electron microscopy. The expression levels of autophagy- and apoptosis-related proteins, such as LC3, Beclin-1, P62, Bax, and Bcl-2, in the mice hippocampus were detected by western blotting. Simultaneously, AMPK/mTOR signaling pathway proteins were detected to understand the potential mechanism. FTY720 had no significant effect on the body weight or fasting blood glucose levels in mice with type 2 diabetes. However, both FTY720 doses improved the cognitive function and hippocampal damage. In addition, the results suggested that FTY720 dramatically decreased P62 and Bax levels and increased LC3 II/LC3 I ratio, Beclin-1, and Bcl-2 expression in the hippocampus of type 2 diabetic mice. FTY720 also affected the expression of the AMPK/mTOR signaling pathway. Thus, FTY720 improved cognitive function and hippocampal pathological changes in type 2 diabetic mice without affecting fasting blood glucose levels. Our results show that FTY720 may exert neuroprotective effects in vivo by enhancing hippocampal autophagy and inhibiting apoptosis via the AMPK/mTOR signaling pathway.

Effects of Sildenafil on Cognitive Function Recovery and Neuronal Cell Death Protection after Transient Global Cerebral Ischemia in Gerbils.

Cerebral ischemic stroke is a major cause of death worldwide due to brain cell death resulting from ischemia-reperfusion injury. However, effective treatment approaches for patients with ischemic stroke are still lacking in clinical practice. This study investigated the potential neuroprotective effects of sildenafil, a phosphodiesterase-5 inhibitor, in a gerbil model of global brain ischemia. We investigated the effects of sildenafil on the expression of glial fibrillary acidic protein and aquaporin-4, which are markers related to astrocyte activation and water homeostasis, respectively. Immunofluorescence analysis showed that the number of cells co-expressing these markers, which was elevated in the ischemia-induced group, was significantly reduced in the sildenafil-treated groups. This suggests that sildenafil may have a potential mitigating effect on astrocyte activation induced by ischemia. Additionally, we performed various behavioral tests, including the open-field test, novel object recognition, Barnes maze, Y-maze, and passive avoidance tests, to evaluate sildenafil's effect on cognitive function impaired by ischemia. Overall, the results suggest that sildenafil may serve as a neuroprotective agent, potentially alleviating delayed neuronal cell death and improving cognitive function impaired by ischemia.

B - 118 Exploration of Supplemental Recognition Measures for the RBANS

Abstract Objective RBANS is a widely used cognitive screener that lacks memory recognition measures for 2 recall tasks. Performance on verbal and visual recognition measures, relative to recall, may help inform clinical decision-making and treatment planning. Our pilot project aims to understand how individuals with valid cognitive data and normal memory functioning perform on newly developed RBANS story and figure memory recognition tests. Method Of those referred for outpatient neuropsychological assessment at a veterans hospital between 2017–2024, 89 received the newly established recognition measures as part of their clinical evaluation. Our analysis included veterans that displayed valid profiles (TOMM trial 1 ≥ 45, n = 53). Assessment occurred 30% face-to-face and 70% telehealth. In addition to key demographic factors listed in table 1, race/ethnicity breakdown included: 92% White, 4% Black, 2% Asian, 2% Hispanic. These veterans were subdivided into 3 intact memory groups: list recall (≥ 25%ile, n = 31), story recall (≥ 25%ile, n = 37), figure recall (≥ 25%ile, n = 42) to determine average recognition performances across domains. Results The individuals with valid cognitive data and normal memory recall performed as listed in table 1. Although our novel story and figure recognition measures differ from those published in Duff et al. (2021), our pilot project data largely overlapped with their reported findings despite demographic differences. Conclusion(s) These novel recognition scores can help establish normal story and figure recognition performance to assist with clinical diagnosis and treatment planning. With greater and more diverse samples, we may be able to establish relative cut points for expected recognition memory performances across intact, amnestic/cortical, and vascular/subcortical.

Maternal separation during lactation affects recognition memory, emotional behaviors, hippocampus and gut microbiota composition in C57BL6J adolescent female mice

BackgroundMaternal separation (MS) in rodents is a paradigm of early life events that affects neurological development in depression. Adolescence is a time of dramatic increases in psychological vulnerability, and being female is a depression risk factor. However, data on whether different MS scenarios affect behavioral deficits and the potential mechanisms in adolescent female mice are limited. MethodsC57BL/6 J female pups were exposed to different MS (no MS, NMS; MS for 15 min/day, MS15; or 180 min/day, MS180) from postnatal day (PND)1 to PND21 and subjected for behavioral tests during adolescence. Behavioural tests, specifically the open field test (OFT), novel object recognition test (NOR) test and tail suspension test (TST), were performed. The expression of proinflammatory cytokines, hippocampal neurogenesis, neuroinflammation, and gut microbiota were also assessed. ResultsThe results showed that MS180 induced emotional behavioral deficits and object recognition memory impairment; however, MS15 promoted object recognition memory in adolescent females. MS180 decreased hippocampal neurogenesis of adolescent females, induced an increase in microgliosis, and increased certain inflammatory factors in the hippocampus, including TNF-α, IL-1β, and IL-6. Furthermore, different MS altered gut microbiota diversity, and alpha diversity in the Shannon index was negatively correlated with the peripheral inflammatory factors TNF-α, IL-1β, and IL-6. Species difference analysis showed that the gut microbiota composition of the phyla Desulfobacterota and Proteobacteria was affected by the MS. LimitationsThe sex differences in adolescent animal and causality of hippocampal neurogenesis and gut microbiota under different MS need to be further analyzed in depression. ConclusionThis study indicates different MS affect recognition memory and emotional behaviors in adolescent females, and gut microbiota-neuroinflammation and hippocampal neurogenesis may be a potential site of early neurodevelopmental impairment in depression.