Effects of agmatine on radial-arm maze memory performance and autistic-like behaviors in a male rat model of autism.

BACKGROUND: Autism spectrum disorder (ASD) is the fastest-growing child neuropsychiatric condition. Cognitive dysfunctions such as memory impairments are experienced by patients along with social disturbances and repetitive/stereotypic movements. We have used the radial arm maze (RAM), for measurement of working and reference memory errors in an animal model of autism. In addition, the potential effects of agmatine, an endogenous NMDA antagonist, on RAM performance and autistic-like behaviors were assessed. METHODS: Autism was modeled by valproic acid (VPA) administration at gestational Day 12.5. Autism-associated behaviors in male offspring were examined in an open field test (OFT) and three-chambered test (TCT) on postnatal days 50-51. Thereafter, the animals were trained in the RAM (PND 55) until they attained the criteria of 80% correct choices during five consecutive trials. Forty-eight hours after the acquisition of criteria, agmatine was injected 30 min before subsequent behavioral testing, which included the retention phase of the RAM, OFT, and TCT. RESULTS: VPA-treated and intact rats showed the same performance in RAM, and acute injection of agmatine rescued social and anxiety-like behavior induced by VPA without the effect on RAM. CONCLUSION: In a rat model of autism, spatial learning, and memory did not change. Agmatine rescued social and anxiety-like behavior in autistic animals.

Oral administration of encapsulated catechin in chitosan-alginate nanoparticles improves cognitive function and neurodegeneration in an aluminum chloride-induced rat model of Alzheimer's disease.

The present study aimed to investigate the effect of catechin-loaded Chitosan-Alginate nanoparticles (NPs) on cognitive function in an aluminum chloride (AlCl3)-induced rat model of Alzheimer's disease (AD). The Catechin-loaded Chitosan-Alginate nanocarriers were synthesized through ionotropic gelation (IG) method. Physio-chemical characterization was conducted with the Zetasizer Nano system, the scanning electron microscope, and the Fourier transform infrared spectroscopy. The experiments were performed over 21 days on six groups of male Wistar rats. The control group, AlCl3 treated group, Catechin group, nanocarrier group, treatment group 1 (AlCl3 + Catechin), and treatment group 2 (AlCl3 + nanocarrier). A behavioral study was done by the Morris water maze (MWM) test. In addition, the level of oxidative indices and acetylcholine esterase (AChE) activity was determined by standard procedures at the end of the study. AlCl3 induced a significant increase in AChE activity, along with a significant decrease in the level of Catalase (CAT) and total antioxidant capacity (TAC) in the hippocampus. Moreover, the significant effect of AlCl3 was observed on the behavioral parameters of the MWM test. Both forms of Catechin markedly improved AChE activity, oxidative biomarkers, spatial memory, and learning. The present study indicated that the administration of Catechin-loaded Chitosan-Alginate NPs is a beneficial therapeutic option against behavioral and chemical alteration of AD in male Wistar rats.

Caloric restriction leading to attenuation of experimental Alzheimer's disease results from alterations in gut microbiome.

BACKGROUND: Caloric restriction (CR) might be effective for alleviating/preventing Alzheimer's disease (AD), but the biological mechanisms remain unclear. In the current study, we explored whether CR caused an alteration of gut microbiome and resulted in the attenuation of cognitive impairment of AD animal model. METHODS: Thirty-week-old male APP/PS1 transgenic mice were used as AD models (AD mouse). CR was achieved by 30% reduction of daily free feeding (ad libitum, AL) amount. The mice were fed with CR protocol or AL protocol for six consecutive weeks. RESULTS: We found that with CR treatment, AD mice showed improved ability of learning and spatial memory, and lower levels of Aß40, Aß42, IL-1ß, TNF-α, and ROS in the brain. By sequencing 16S rDNA, we found that CR treatment resulted in significant diversity in composition and abundance of gut flora. At the phylum level, Deferribacteres (0.04%), Patescibacteria (0.14%), Tenericutes (0.03%), and Verrucomicrobia (0.5%) were significantly decreased in CR-treated AD mice; at the genus level, Dubosiella (10.04%), Faecalibaculum (0.04%), and Coriobacteriaceae UCG-002 (0.01%) were significantly increased in CR-treated AD mice by comparing with AL diet. CONCLUSIONS: Our results demonstrate that the attenuation of AD following CR treatment in APP/PS1 mice may result from alterations in the gut microbiome. Thus, gut flora could be a new target for AD prevention and therapy.

[Mechanism of electroacupuncture for vascular dementia based on proteomics].

OBJECTIVE: To explore the potential mechanism of electroacupuncture (EA) for vascular dementia (VD) using tandem mass tag (TMT) quantitative proteomics technology. METHODS: Among 80 male SPF SD rats, 78 rats which met the selection criteria through the Morris water maze test were selected and randomly divided into a sham surgery group (18 rats) and a surgery group (60 rats). VD model was established by four-vessel occlusion (4-VO) method in the surgery group, and 36 rats with successful modeling were randomly assigned to a model group (18 rats) and an EA group (18 rats). Each group was further divided into three subgroups based on intervention duration, with each subgroup containing 6 rats. Seven days after model establishment, the EA group received EA intervention at left and right "Sishencong" (EX-HN 1) and bilateral "Fengchi" (GB 20), with continuous wave at a frequency of 2 Hz and current intensity of 1 mA, daily for 30 min, with subgroups receiving EA for 7, 14, or 21 d respectively. Cognitive function before and after interventions was assessed using Morris water maze. Proteomic analysis was conducted on the optimal EA subgroup and corresponding sham surgery and model subgroups, identifying differentially expressed proteins and analyzing them through bioinformatics. Differentially expressed target proteins was performed using parallel reaction monitoring (PRM) and Western blot techniques. RESULTS: Compared to the sham surgery group, the model group exhibited prolonged escape latency and reduced number of platform crossings (P<0.01); compared with model group, the EA group showed reductions in escape latency and increased platform crossings after 7, 14, and 21 days of intervention (P<0.01, P<0.05). Compared to the 7 and 14-day intervention, the rats in the EA group of 21-day intervention showed the most significant improvements in reductions of escape latency and increased platform crossings (P<0.01, P<0.05), and was selected for further proteomic, PRM analyses, and Western blot validation. Compared to the sham surgery group, the model group displayed 71 differentially expressed proteins, with 50 up-regulated and 21 down-regulated proteins; compared to the model group, the EA group had 54 differentially expressed proteins, with 30 up-regulated and 24 down-regulated proteins. Functional enrichment and clustering analyses indicated that these proteins were primarily associated with cellular processes, metabolic processes, phagocytosis recognition, immune response, and regulation of extracellular matrix, etc. Enrichment was observed in the mammalian target of rapamycin (mTOR) signaling pathway and neurotrophic factors signaling pathways, involving glycogen synthase kinase 3ß (GSK3ß) and mitogen-activated protein kinase kinase 2 (Map2k2), with PRM and Western blot findings consistent with the proteomic results. Which meant that compared with the model group, the protein expression of GSK3ß and Map2k2 of hippocampus was increased in the EA group (P<0.01, P<0.05). CONCLUSION: EA at "Sishencong" (EX-HN 1) and "Fengchi" (GB 20) could improve cognitive function in VD rats, with the mechanism involving multiple targets and pathways, potentially related to GSK3ß, Map2k2 proteins, and the mTOR and neurotrophic factor signaling pathways.

Astaxanthin reduces TBPH-induced neurobehavioral deficits in mice by the ROS-ERK1/2-FOS pathway.

The persistence of the novel brominated flame retardant, bis(2-ethylhexyl)-3,4,5,6-tetrabromophthalate (TBPH), in the environment and its potential for bioaccumulation in living organisms, including humans, further exacerbate its health risks. Therefore, ongoing research is crucial for fully understanding the extent of TBPH's neurotoxicity and for developing effective mitigation strategies. This study aims to investigate the potential neurotoxicity of TBPH on mouse neurobehavior and to evaluate the protective effects of the natural antioxidant astaxanthin (AST) against TBPH-induced neurotoxicity. The results indicate that exposure to TBPH can lead to a decline in learning and memory abilities and abnormal behaviors in mice, which may be associated with oxidative stress responses and apoptosis in the hippocampus. TBPH may disrupt the normal function of hippocampal neurons by activating the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. Mice exposed to TBPH treated with AST showed improved learning and memory abilities in the Morris water maze (MWM) and Step-down test (SDT). AST, through its antioxidant action, was able to significantly reduce the increase in reactive oxygen species (ROS) levels induced by TBPH, the increased expression of apoptosis markers, and the activation of the ERK1/2-FOS signaling pathway, alleviating TBPH-induced apoptosis in hippocampal neurons and improving neurobehavioral outcomes. These findings suggest that AST may alleviate the neurotoxicity of TBPH by modulating molecular events related to apoptosis and the ERK1/2-FOS signaling pathway. Thus, this study provides evidence for AST as a potential interventional strategy for the prevention or treatment of cognitive decline associated with environmental neurotoxicant exposure.

Astaxanthin Rescues Memory Impairments in Rats with Vascular Dementia by Protecting Against Neuronal Death in the Hippocampus.

Vascular dementia (VaD) is a cognitive disorder characterized by a decline in cognitive function resulting from cerebrovascular disease. The hippocampus is particularly susceptible to ischemic insults, leading to memory deficits in VaD. Astaxanthin (AST) has shown potential therapeutic effects in neurodegenerative diseases. However, the mechanisms underlying its protective effects in VaD and against hippocampal neuronal death remain unclear. In this study, We used the bilateral common carotid artery occlusion (BCCAO) method to establish a chronic cerebral hypoperfusion (CCH) rat model of VaD and administered a gastric infusion of AST at 25 mg/kg per day for 4 weeks to explore its therapeutic effects. Memory impairments were assessed using Y-maze and Morris water maze tests. We also performed biochemical analyses to evaluate levels of hippocampal neuronal death and apoptosis-related proteins, as well as the impact of astaxanthin on the PI3K/Akt/mTOR pathway and oxidative stress. Our results demonstrated that AST significantly rescued memory impairments in VaD rats. Furthermore, astaxanthin treatment protected against hippocampal neuronal death and attenuated apoptosis. We also observed that AST modulated the PI3K/Akt/mTOR pathway, suggesting its involvement in promoting neuronal survival and synaptic plasticity. Additionally, AST exhibited antioxidant properties, mitigating oxidative stress in the hippocampus. These findings provide valuable insights into the potential therapeutic effects of AST in VaD. By elucidating the mechanisms underlying the actions of AST, this study highlights the importance of protecting hippocampal neurons and suggests potential targets for intervention in VaD. There are still some unanswered questions include long-term effects and optimal dosage of the use in human. Further research is warranted to fully understand the therapeutic potential of AST and its application in the clinical treatment of VaD.

The Insulin Sensitizer KBP-336 Prevents Diabetes-Induced Cognitive decline in ZDF Rats.

BACKGROUND AND OBJECTIVES: Diabetes and especially insulin resistance are associated with an increased risk of developing cognitive dysfunction, making anti-diabetic drugs an interesting therapeutic option for the treatment of neurodegenerative disorders. Dual amylin and calcitonin receptor agonists (DACRAs) elicit beneficial effects on glycemic control and insulin sensitivity. However, whether DACRAs affect cognition is unknown. DESIGN AND INTERVENTION: Zucker Diabetic Fatty rats were treated with either the DACRA KBP-336 (4.5 nmol/kg Q3D), the amylin analog AM1213 (25 nmol/kg QD), or vehicle for 18 weeks. Further, the efficacy of a late KBP-336 intervention was evaluated by including a group starting treatment on day 30. Glucose control and tolerance were evaluated throughout the study and spatial learning and memory were evaluated by Morris Water Maze after 17 weeks of treatment. RESULTS: When evaluating spatial learning, rats receiving KBP-336 throughout the study performed significantly better than AM1213, vehicle, and late intervention KBP-336. Both KBP-336 and AM1213 treatments improved spatial memory compared to the vehicle. The overall performance in the cognitive tests was reflected in the treatment efficacy on glycemic control, where KBP-336 was superior to AM1213. CONCLUSION: In summary, the DACRA KBP-336 ameliorates diabetes-induced spatial learning and memory impairment in diabetic rats. Further, KBP-336 improves long-term glycemic control superior to the amylin analog AM1213. Taken together, KBP-336 is, due to its anti-diabetic and insulin-sensitizing properties, a promising candidate for the treatment of cognitive impairments.

Evaluation of ivermectin and vitamin E based combination with antiseizure rufinamide drug for mitigation of pentylenetetrazole-induced kindling, behavioral challenges and histopathological aberrations.

Pentylenetetrazole- (PTZ)-induced kindling is a broadly used experimental model to evaluate the impact of antiseizure drugs and their novel combination on seizure progression. The current study aimed to evaluate the anti-kindling effects of ivermectin (IVM) and rufinamide (RUFI) alone and their combination with vitamin E. The mice were administered 11 injections of PTZ (40 mg/kg) followed by assessment for anxiety-like behavior and cognitive abilities in a series of behavior tests with subsequent brain isolation for biochemical and histopathological evaluation. The outcomes showed a marked protection by IVM + RUFI (P<0.001) from kindling progression, anxiety-like behavior and cognitive deficit. However, additional supplementation with vitamin E worked superior to duo therapy as these mice were noted to be most fearless to visiting open, illuminated and elevated zones of open field, light/dark and elevated-plus maze (P<0.0001). Further, they showed marked remembrance of the familiar milieu in y-maze (P<0.01) and novel objection recognition (P<0.05) tests. Additionally, their recollection of aversive stimuli in passive avoidance and spatial memory in Morris water maze were evident (P<0.0001), in comparison to kindled mice. The IVM + RUFI duo therapy and its co-administration with vitamin E prevented kindling-triggered oxidative stress in brains and neuronal damage in hippocampus. We conclude that the benefits of the co-administration of vitamin E might be the results of antioxidant and anti-inflammatory effects of vitamin E which might be potentiating the antiseizure effects of RUFI and GABA-A modulating potential by ivermectin.

Unbiased analysis of spatial learning strategies in a modified Barnes maze using convolutional neural networks.

Assessment of spatial learning abilities is central to behavioral neuroscience and a useful tool for animal model validation and drug development. However, biases introduced by the apparatus, environment, or experimentalist represent a critical challenge to the test validity. We have recently developed the Modified Barnes Maze (MBM) task, a spatial learning paradigm that overcomes inherent behavioral biases of animals in the classical Barnes maze. The specific combination of spatial strategies employed by mice is often considered representative of the level of cognitive resources used. Herein, we have developed a convolutional neural network-based classifier of exploration strategies in the MBM that can effectively provide researchers with enhanced insights into cognitive traits in mice. Following validation, we compared the learning performance of female and male C57BL/6J mice, as well as that of Ts65Dn mice, a model of Down syndrome, and 5xFAD mice, a model of Alzheimer's disease. Male mice exhibited more effective navigation abilities than female mice, reflected in higher utilization of effective spatial search strategies. Compared to wildtype controls, Ts65Dn mice exhibited delayed usage of spatial strategies despite similar success rates in completing this spatial task. 5xFAD mice showed increased usage of non-spatial strategies such as Circling that corresponded to higher latency to reach the target and lower success rate. These data exemplify the need for deeper strategy classification tools in dissecting complex cognitive traits. In sum, we provide a machine-learning-based strategy classifier that extends our understanding of mice's spatial learning capabilities while enabling a more accurate cognitive assessment.

Age-Related Effects of AT1 Receptor Antagonist Losartan on Cognitive Decline in Spontaneously Hypertensive Rats.

Both hypertension and aging are known to increase the vulnerability of the brain to neurovascular damage, resulting in cognitive impairment. The present study investigated the efficacy of the antihypertensive drug losartan on age- and hypertension-associated cognitive decline and the possible mechanism underlying its effect in spontaneously hypertensive rats (SHRs). Losartan was administered (10 mg/kg, i.p. for 19 days) to 3- and 14-month-old SHRs. Age-matched Wistar rats were used as controls. Working memory, short-term object recognition, and spatial memory were assessed using the Y-maze, object recognition test (ORT) and radial arm maze (RAM) test. The expression of markers associated with aging, oxidative stress, and memory-related signaling was assessed in the frontal cortex (FC) and hippocampus. Motor activity measured over 24 h was not different between groups. Middle-aged vehicle-treated SHRs showed poorer performance in spontaneous alternation behavior (SAB) and activity in the first Y-maze test than their younger counterparts, suggesting age-related reduced "decision making" and reactivity in a novel environment. Losartan improved the age- and hypertension-induced decline in short-term recognition and spatial memory measured in the ORT and the second Y-maze test, particularly in the middle-aged rats, but was ineffective in the young adult rats. Changes in memory and age-related markers such as cAMP response element-binding protein (CREB) and amyloid-ß1-42 (Aß1-42) and increased oxidative stress were observed in the hippocampus but not in the FC between young adult and middle-aged vehicle-treated SHRs. Losartan increased CREB expression while reducing Aß1-42 levels and concomitant oxidative stress in middle-aged SHRs compared with vehicle-treated SHRs. In conclusion, our study highlights the complex interplay between hypertension, aging, and cognitive impairment. It suggests that there is a critical time window for therapeutic intervention with angiotensin II type 1 receptor blockers.

Apple polysaccharide improves age-matched cognitive impairment and intestinal aging through microbiota-gut-brain axis.

The Apple polysaccharides (AP), extracted from the fruit of apple, has been used to treat multiple pathological diseases. In this study, we evaluated the effects of AP on cognitive impairment and intestinal aging in naturally aging mice. As a result, it was found that AP could improve spatial learning and memory impairment in aging mice through the Morris water maze experiment. Additionally, AP intervention can upregulate the expression of nerve growth factor (BDNF), postsynaptic marker (PSD95), and presynaptic marker (SYP) proteins. Moreover, AP can enhance total antioxidant capacity, reduce the level of pro-inflammatory cytokine, and inhibit the activation of the NF-κB signaling pathway, exerting anti-inflammatory and antioxidant functions. And the administration of AP restored intestinal mucosal barrier function, reduced the expression of aging and apoptosis related proteins. The administration of AP also altered the gut microbiota of mice. At the genus level, AP decreased the abundance of Helicobacter and Bilophila, while increased the abundance of Lactobacillus and Bacteroides. In summary, these data demonstrate that AP treatment can alleviate cognitive impairment, oxidative stress, and inflammatory reactions, repair the intestinal mucosal barrier, reduce intestinal aging, and alter specific microbial characteristics, ultimately improving the health of the elderly.

Propofol improves sleep deprivation-induced sleep structural and cognitive deficits via upregulating the BMAL1 expression and suppressing microglial M1 polarization.

BACKGROUND: Sleep deprivation (SD) is a growing global health problem with many deleterious effects, such as cognitive impairment. Microglia activation-induced neuroinflammation may be an essential factor in this. Propofol has been shown to clear sleep debt after SD in rats. This study aims to evaluate the effects of propofol-induced sleep on ameliorating sleep quality impairment and cognitive decline after 48 h SD. METHODS: Almost 8-12-week-old rats were placed in the SD system for 48 h of natural sleep or continuous SD. Afterwards, rats received propofol (20 mg·kg-1·h-1, 6 h) via the tail or slept naturally. The Morris water maze (MWM) and Y-maze test assessed spatial learning and memory abilities. Rat EEG/EMG monitored sleep. The expression of brain and muscle Arnt-like protein 1 (BMAL1), brain-derived neurotrophic factor (BDNF) in the hippocampus and BMAL1 in the hypothalamus were assessed by western blot. Enzyme-linked immunosorbent assay detected IL-6, IL-1ß, arginase 1 (Arg1), and IL-10 levels in the hippocampus. Immunofluorescence was used to determine microglia expression as well as morphological changes. RESULTS: Compared to the control group, the sleep-deprived rats showed poor cognitive performance on both the MWM test and the Y-maze test, accompanied by disturbances in sleep structure, including increased total sleep time, and increased time spent and delta power in non-rapid eye movement sleep. In addition, SD induces abnormal expression of the circadian rhythm protein BMAL1, activates microglia, and causes neuroinflammation and nerve damage. Propofol reversed these changes and saved sleep and cognitive impairment. Furthermore, propofol treatment significantly reduced hippocampal IL-1ß and IL-6 levels, increased BDNF, Arg1, and IL-10 levels, and switched microglia surface markers from the inflammatory M1 type to the anti-inflammatory M2 type. CONCLUSION: Propofol reduces SD-induced cognitive impairment and circadian rhythm disruption, possibly by lowering neuronal inflammation and switching the microglia phenotype from an M1 to an M2 activated state, thus exerting neuroprotective effects.

The Influence of Maternal Hypoxia and Buspirone during Pregnancy on Cognitive Abilities and a Stress Response in Adult Male Offspring.

Spatial learning, memory, and reactivity of the hypothalamic-pituitary-adrenocortical system (HPA axis) were studied in adult male rats, whose mothers during pregnancy were subjected to acute moderate normobaric hypoxia, or repeated injections of buspirone, an agonist of type 1A serotonergic receptors (5HT1A), or their combination. Prenatal treatment with buspirone in rats with prenatal hypoxia impaired learning ability during the first day of 5-day training. A decrease in the effectiveness of long-term memory in comparison with short-term memory was revealed in two groups of rats: prenatal treatment with buspirone in combination with hypoxia and injection of physiological saline without hypoxia. The effectiveness of long-term memory and the level of corticosterone in response to stress did not differ between the groups, which can indicate adaptation of the 5HT1A receptor and the HPA axis to the prenatal buspirone and normobaric hypoxia during ontogeny.

CRY2 mediates the cognitive decline induced by sleep deprivation in 5xFAD mice.

BACKGROUND: Cryptochrome-2 (CRY2) is a core rhythm gene that plays a crucial role in DNA damage repair. The present study investigated the potential role of CRY2 in mediating sleep deprivation-induced cognitive decline in 5xFAD mice. METHODS: To assess the effects of SD on different brain regions of the mouse brain, we used 18F FDG PET-CT. Cognitive function was evaluated using the Morris water maze test and Y-maze. Lentivirus was used for the overexpression of CRY2, and small interfering RNA (siRNA) was used for the downregulation of CRY2 to verify the effect of CRY2. We used qRT‒PCR and Western blotting to identify the downstream factors of CRY2 and evaluated the cognitive function of mice to confirm the effects of these factors. RESULTS: The AD mice exhibited cognitive decline after 21 days of SD and had higher expression of CRY2 compared to AD mice with normal sleep. Overexpression of CRY2 led to decreased cognitive function in AD mice, and the downregulation of CRY2 attenuated the SD-induced cognitive decline in AD mice. CRY2 reduced the expression and function of CISH, which reduced the inhibition of STAT1 phosphorylation and led to synaptic dysfunction. CISH overexpression attenuated the impairing effect of sleep deprivation on cognitive function in AD mice. Furthermore, 18F FDG PET-CT revealed that SD significantly reduced glucose metabolism in different brain regions of AD mice. CONCLUSION: Our study demonstrated that sleep deprivation upregulated CRY2 in the hippocampus of AD mice, which resulted in synaptic dysfunction by decreasing CISH-mediated STAT1 phosphorylation.

Metabolomics study to reveal cognitive improvement with treatment of Scrophularia buergeriana.

Population aging around the world is rapidly progressing; as a result, cognitive decline developing into dementia is becoming a social problem. There is no drug that can cure dementia, and though drugs that alleviate the symptoms of dementia have been developed, they also have side effects. Therefore, we conducted a study on improving cognitive function using natural products that have secured safety. We confirmed the effect of an extract of Scrophularia buergeriana on scopolamine-induced cognitive impairment through mouse behavioral experiments, and we observed metabolic changes in the cortex and hippocampus via brain tissue dissection after the behavioral experiment. Mitigating effects of S. buergeriana on cognitive impairment caused by scopolamine were observed in passive avoidance and Morris water maze tests. A metabolic analysis revealed biomarkers related to the alleviating effect of cognitive impairment. Niacinamide, tyrosine, uridine, and valine in the cortex and GABA, choline, creatine, formate, fumarate, hypoxanthine, leucine, myo-inositol, pyroglutamate, and taurine in the hippocampus were identified as biomarker candidates for recovering cognitive impairment. In addition to behavioral experiments, this metabolomics study using specific regions of the brain may be helpful in understanding the effects of cognitive improvement.

Protective effects of selegiline against amyloid beta-induced anxiety-like behavior and memory impairment.

BACKGROUND: Alzheimer's disease (AD) is a complex and common neurodegenerative disorder. The present study aimed to investigate the potential effects of selegiline (SEL) on various aspects of memory performance, anxiety, and oxidative stress in an AD rat model induced by intracerebroventricular injection of amyloid beta1-42 (Aß1-42). METHODS: Oral administration of SEL at a dose of 0.5 mg/kg/day was performed for 30 consecutive days. Following the 30 days, several tests, including the open-field, elevated plus-maze, novel object recognition, Morris water maze, and passive avoidance learning were conducted to assess locomotor activity, anxiety-like behavior, recognition memory, spatial memory, and passive avoidance memory, respectively. RESULTS: The results indicate that the induction of AD in rats led to recognition memory, spatial memory, and passive avoidance memory impairments, as well as increased anxiety. Additionally, the AD rats exhibited a decrease in total antioxidant capacity and an increase in total oxidant status levels, suggesting an imbalance in oxidative-antioxidant status. However, the administration of SEL improved memory performance, reduced anxiety, and modulated oxidative-antioxidant status in AD rats. CONCLUSIONS: These findings provide evidence that SEL may alleviate anxiety-like behavior and cognitive deficits induced by Aß through modulation of oxidative-antioxidant status.

Replay of incidentally encoded novel odors in the rat.

Although events are not always known to be important when they occur, people can remember details about such incidentally encoded information using episodic memory. Sheridan et al. (2024) argued that rats replayed episodic memories of incidentally encoded information in an unexpected assessment of memory. In one task, rats reported the third-last item in an explicitly encoded list of trial-unique odors. In a second task, rats foraged in a radial maze in the absence of odors. On a critical test, rats foraged in the maze, but scented lids covered the food. Next, memory of the third-last odor was assessed. The rats correctly answered the unexpected question. Because the odors used in the critical test were the same as those used during training, automatically encoding odors for the purpose of taking an upcoming test of memory (stimulus generalization) may have been encouraged. Here, we provided an opportunity for incidental encoding of novel odors. Previously trained rats foraged in the radial maze with entirely novel odors covering the food. Next, memory of the third-last odor was assessed. The rats correctly answered the unexpected question. High accuracy when confronted with novel odors provides evidence that the rats did not automatically encode odors for the purpose of taking an upcoming test, ruling out stimulus generalization. We conclude that rats encode multiple pieces of putatively unimportant information, and later replayed a stream of novel episodic memories when that information was needed to solve an unexpected problem.

The selective butyrylcholinesterase inhibitor UW-MD-95 shows symptomatic and neuroprotective effects in a pharmacological mouse model of Alzheimer's disease.

AIMS: Alzheimer's disease (AD) is a devastating dementia characterized by extracellular amyloid-ß (Aß) protein aggregates and intracellular tau protein deposition. Clinically available drugs mainly target acetylcholinesterase (AChE) and indirectly sustain cholinergic neuronal tonus. Butyrylcholinesterase (BChE) also controls acetylcholine (ACh) turnover and is involved in the formation of Aß aggregates and senile plaques. UW-MD-95 is a novel carbamate-based compound acting as a potent pseudo-irreversible BChE inhibitor, with high selectivity versus AChE, and showing promising protective potentials in AD. METHODS: We characterized the neuroprotective activity of UW-MD-95 in mice treated intracerebroventricularly with oligomerized Aß25-35 peptide using behavioral, biochemical, and immunohistochemical approaches. RESULTS: When injected acutely 30 min before the behavioral tests (spontaneous alternation in the Y-maze, object recognition, or passive avoidance), UW-MD-95 (0.3-3 mg/kg) showed anti-amnesic effects in Aß25-35-treated mice. When injected once a day over 7 days, it prevented Aß25-35-induced memory deficits. This effect was lost in BChE knockout mice. Moreover, the compound prevented Aß25-35-induced oxidative stress (assessed by lipid peroxidation or cytochrome c release), neuroinflammation (IL-6 and TNFα levels or GFAP and IBA1 immunoreactivity) in the hippocampus and cortex, and apoptosis (Bax level). Moreover, UW-MD-95 significantly reduced the increase in soluble Aß1-42 level in the hippocampus induced by Aß25-35. CONCLUSION: UW-MD-95 appeared as a potent neuroprotective compound in the Aß25-35 model of AD, with potentially an impact on Aß1-42 accumulation that could suggest a novel mechanism of neuroprotection.

The Dose-Dependent Effect of Fractionated γ-Radiation on Anxiety-Like Behavior in Neonatal Mice.

High doses of ionizing radiation are the risk factor of cognitive dysfunction and anxiety disorders developing in humans and experimental animals. However, the data on the effect of low doses, especially in case of chronic or fractionated exposure, is limited and contradictory. Here we studied the effect of fractionated γ-radiation at cumulative doses of 0.1, 1, and 5 Gy on the parameters of the anxiety-like behavior in neonatal C57BL/6 mice. The anxiety was evaluated using the marble burying test and elevated plus maze. Fractionated irradiation resulted in dose-dependent changes in mouse behavior: the low dose caused an increase in anxiety, wherein the dose raise led to the decrease in anxiety-like behavior indicators compared to non-irradiated animals.