Non-spatial Memory Research Articles

Doxorubicin Effects on Cognitive Impairment and the Microscopic View of Brain Structures in Rats

The creation of a validated model of the “chemical brain” in laboratory animals is an urgent task, the solution of which will optimize the search for new drugs for the prevention and pharmacological correction of delayed effects of chemotherapy on the central nervous system. The aim of the work has been to assess the effect of doxorubicin after systemic course administration on behavioral reactions and the microscopic view of the cerebral cortex and hippocampus in rats.Doxorubicin was administered intraperitoneally to male rats at doses of 5 and 6 mg/kg, once a week, for 28 days. The behavioral reactions of the animals were assessed, and pathomorphological studies of the cerebral cortex and hippocampus were carried out.Doxorubicin at doses of 5 and 6 mg/kg causes inhibition of motor activity in the “Open Field” test, impairment of non-spatial and spatial memory in the “New Object Recognition” and “Y-Maze” tests, respectively. Doxorubicin at these doses increases the severity of vascular congestion and perivascular edema in the cerebral cortex and hippocampus.Doxorubicin at doses of 5 and 6 mg/kg causes impairment of cognitive functions in rats in tests assessing non-spatial and spatial memory, as well as microcirculation disorders in the cerebral cortex and hippocampus of rats.

AMPA and NMDA Receptors in Hippocampus of Rats with Fluoride-Induced Cognitive Decline

This experimental study was performed to evaluate the alterations in the expression of a few subunits composing glutamate AMPA (a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and NMDA (N-methyl-D-aspartate) receptors in the hippocampal cells of Wistar rats in response to long-term fluoride (F-) exposure. The animals were given water with background 0.4 (control), 5, 20, and 50 ppm F- (as NaF) for 12 months. The cognitive capacities of rats were examined by novel object recognition (NOR), Y-maze test, and Morris water maze tests. RT-qPCR and Western blotting techniques were used to evaluate the expression of different AMPA and NMDA subunits at transcriptional and translational levels, respectively. Long-term F- poisoning disturbed the formation of hippocampus-dependent working spatial and long-term non-spatial memory. The expression of Gria1, Gria2, and Gria3 genes encoding different subunits of AMPA receptors were comparable in hippocampi of control and F--exposed animals, although the levels of both Grin2a and Grin2b mRNA increased. Long-term F- intake enhanced the ratio of phospho-GluA1/total-GluA1 proteins in subcellular fraction enriched with cytosolic proteins, while decreased content of GluA2 but elevated level of GluA3 were observed in subcellular fraction enriched with membrane proteins. Such changes were accompanied by increased phosphorylation of GluN2A and GluN2B subunits, higher ratios of GluN2A/GluN1 and GluN2B/GluN1 proteins in the cytosol, and GluN2A/GluN2B ratio in membranes. These changes indicate the predominance of Ca2+-permeable AMPARs in membranes and a shift between different NMDARs subunits in hippocampal cells of F--exposed rats, which is typical for neurodegeneration and can at least partially underly the observed disturbances in cognitive capacities of animals.

Neuroprotective mechanisms and ameliorative activities of quercetin in cisplatin-induced cerebellum neurotoxicity in rat models

Cisplatin (CP) is a highly effective antitumor agent, but its clinical use is limited due to critical adverse reactions including neurotoxicity. Quercetin (QC) is a naturally occurring phytochemical with promising bioactive effects. This study investigated the Neuroprotective mechanisms and ameliorative activities of quercetin in cisplatin-induced cerebellum neurotoxicity in rat models.The rats were randomly divided into five groups of six (n = 6) rats. Group A, served as control. Group B, received a single dose of 10 mg/kg body weight (bwt) of CP (i.p.) on the first day. Group C received 30 mg/kg bwt of QC. Group D received a single dose of 10 mg/kg bwt CP on the first day followed by 30 mg/kg bwt of QC. Group E received 30 mg/kg bwt of QC per day followed by a single dose of 10 mg/kg bwt of CP on the last day. The treatment lasted for 35 days after which the novel-object recognition memory test (NORT) was used to assess non-spatial memory function. Brain neurochemical status was assessed and brain tissues were processed for histology.Quercetin increased weight loss and cognitive performance in CP-treated rats by enhancing the exploration of unfamiliar objects. Quercetin protects the brain from CP-mediated alterations in oxidative status, as well as brain metabolic enzyme indicators. It also decreased IL-6, IL-1, and TNF-α, and NF-ĸB expression, restored brain metabolic enzyme activities, increased neurotransmitters, and prevented neuromorphological alterations.In conclusion, quercetin protects rats’ brains against CP-induced cerebellum neurotoxicity via oxidative stress inhibition and down-regulation of inflammation.

Lateral Entorhinal Cortex Dysfunction in Alzheimer's Disease Mice.

In Alzheimer's disease (AD), the formation of amyloid beta and neurofibrillary tangles (NFTs) leads to neuronal loss in entorhinal cortex (EC), a crucial brain region involved in memory and navigation. These pathological changes are concurrent with the onset of memory-related issues in AD patients with symptoms of forgetfulness such as misplacing items, disorientation in familiar environments etc. The lateral EC (LEC) is associated with non-spatial memory processing including object recognition. Since in LEC, neurons fire in response to objects (object cells) and at locations previously occupied by objects (trace cells), pathology in this region could lead to dysfunction in object location coding. In this paper we show that a transgenic mouse model, EC-App/Tau, which expresses both APP and tau primarily in the EC region, have deficits in LEC-specific memory tasks. Using in vivo single-unit electrophysiology recordings we show that the LEC neurons are hyperactive with low information content and high sparsity compared to the controls indicating poor firing fidelity. We finally show that object cells and trace cells fire less precisely in the EC-App/Tau mice compared to controls indicating poor encoding of objects. Overall, we show that AD pathology causes erratic firing of LEC neurons and object coding defects leading to LEC-specific memory impairment.

Joint administration of sub-threshold doses of the acetylcholinesterase inhibitor donepezil with those of the NMDA receptor antagonist ketamine improved rats’ recognition memory abilities

Alzheimer’s Disease (AD) is a serious progressive neurodegenerative illness conducting to the decay of cognitive functions. A few drugs have been approved for the therapy of AD, including the acetylcholinesterase inhibitors (AChEIs) like donepezil. Their efficiency, however, is modest and their application is associated with toxicity. Recently, the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine, a rapidly acting antidepressant, has been proposed as a potential agent for the treatment of AD. The present study was designed to investigate the effects exerted by the combination of sub-threshold doses of donepezil with those of ketamine on rats’ recognition memory abilities. For these experiments, the object recognition task (ORT) and the object location task (OLT), two procedures assessing non-spatial and spatial recognition memory respectively in rodents were used. Post-training acute administration of inactive doses of donepezil (0.3 mg/kg) and ketamine (1 mg/kg) counteracted non-spatial and spatial recognition memory impairments. The present findings, although preliminary, propose that the combined administration of ketamine and donepezil could represent a new strategy for the therapy of memory disorders, a common feature of AD patients.

Differences in memory performance: The effects of sex and reproductive experience on object recognition memory in high- and low-yawning Sprague‒Dawley rats

The novel object recognition (NOR) test is an efficient way to measure nonspatial memory in rodents. The NOR performance of female and male rats is sexually dimorphic because memory performance is better in the former than in the latter. In females, maternal experience enhances spatial memory. We used the NOR test to evaluate short- and long-term recognition memory in both sexes in the high- and low-yawning sublines of rats (HY and LY, respectively), which were generated via a strict inbreeding process from the Sprague‒Dawley (SD) strain for more than ninety generations. Additionally, we evaluated the effect of maternal experience using nulliparous, primiparous, biparous, and multiparous HY, LY and SD dams. Our results revealed that LY rats presented less thigmotaxis, with lower central square crosses and more vertical exploration in the open-field arena, suggesting that they experienced anxiety. Additionally, LY males performed significantly better than LY females in short- and long-term NOR memory, and LY males performed significantly better than SD rats did. Among females, two maternal experiences negatively affected short-term memory in the LY and HY sublines with respect to primiparous dams, and HY dams had better memory performance in the NOR test than did SD dams. Our findings suggest that the yawning sublines are suitable for studying the neurobiological basis of different memory processes under different endocrine conditions in highly inbred groups of rats.

Acetate enhances spatial memory in females via sex- and brain region-specific epigenetic and transcriptional remodeling.

Metabolic control of chromatin and gene expression is emerging as a key, but largely unexplored aspect of gene regulation. In the brain, metabolic-epigenetic interactions can influence critical neuronal functions. Here, we use a combination of behavioral, proteomic and genomic approaches to demonstrate that the intermediary metabolite acetate enhances memory in a brain region- and sex-specific manner. We show that acetate facilitates the formation of dorsal hippocampus-dependent spatial memories in female but not in male mice, while having no effect on cortex-dependent non-spatial memories in either sex. Acetate-enhanced spatial memory is driven by increased acetylation of histone variant H2A.Z, and upregulation of genes implicated in spatial learning in the dorsal hippocampus of female mice. In line with the sex-specific behavioral outcomes, the effect of acetate on dorsal hippocampal histone modifications and gene expression shows marked differences between the sexes during critical windows of memory formation (consolidation and recall). Overall, our findings elucidate a novel role for acetate, a ubiquitous and abundant metabolite, in regulating dorsal hippocampal chromatin, gene expression and learning, and outline acetate exposure as a promising new approach to enhance memory formation.

Embelin Mitigates Amyloid-β-Induced Neurotoxicity and Cognitive Impairment in Rats: Potential Therapeutic Implications for Alzheimer's Disease.

Alzheimer's disease (AD) is a significant form of dementia. Embelin (EMB) is a natural compound with varied actions that could help prevent AD pathology. Herein, we have investigated the neuroprotective potential of EMB against Aβ1-42-induced neurotoxicity in rats. In this experiment, Alzheimer-like dementia was induced in rats by infusing Aβ1-42 oligomers directly into the brain's ventricles. Subsequently, the Aβ1-42-intoxicated rats received treatment with varying doses of EMB (2.5, 5, and 10mg/kg, administered intraperitoneally) over 2weeks. The spatial and non-spatial memory of animals was assessed at different time intervals, and various biochemical, neurochemical, and neuroinflammatory parameters in the hippocampal brain tissue of the rats were analyzed. Infusion of Aβ1-42 in rat brain caused cognitive impairment and was accompanied by increased acetylcholinesterase activity, oxidative stress, and elevated levels of pro-inflammatory cytokines (such as TNF-α, IL-1β, and IL-6) in the hippocampal tissue. Moreover, a significant decline in the levels of monoamines and an imbalance of GABA and glutamate levels were also observed. EMB treatment significantly mitigated Aβ1-42-induced cognitive deficit and other biochemical changes, including Aβ levels. The EMB-treated rats showed improved learning and consolidation of memory. EMB also attenuated Aβ-induced oxidative stress and neuroinflammation and restored the levels of monoamines and the balance between GABA and glutamate. The observed cognitive benefits following EMB treatment in Aβ1-42-infused rats may be attributed to its antioxidant and anti-inflammatory properties and ability to restore hippocampal neurochemistry and Aβ levels. The above findings indicate the therapeutic potential of EMB in neurodegenerative pathologies associated with cognitive decline, such as Alzheimer's disease.

Interaction between visual working memory and upright postural control in young adults: an event-related potential study based on the n-back paradigm.

As a part of the overall information-processing system of the brain, postural control is related to the cognitive processes of working memory. Previous studies have suggested that cognitive tasks and postural control processes can compete for resources in common brain areas, although there is an "inverted U" relationship between arousal level and behavioral control - the arousal level of individuals changes when performing cognitive tasks. However, the exact neural connections between the two are unclear. This may be related to the nature of cognitive tasks. Some studies believe that posture occupies not only spatial information processing resources but also visual non-spatial information processing resources. Other studies believe that posture control only occupies spatial information processing resources in the central system, but does not occupy non-spatial information processing resources. Previous studies used different cognitive task materials and reached different conclusions. In this study, we used the same visuospatial and non-spatial materials, the n-back visual working memory paradigm, the event-related potential technique to investigate the effects of visuospatial and non-spatial working memory tasks on adolescents' postural control under different cognitive loads. The results of this study showed that in both visuospatial and non-spatial conditions, the N1 effect of the parieto-occipital lobe was larger during upright posture than in the sitting position (160-180 ms), the P300 effect of the central parieto-occipital region (280-460 ms) was induced by working memory in different postures, and the P300 wave amplitude was higher in the sitting position than in the upright position. We demonstrated that upright postural control enhances early selective attention but interferes with central memory encoding, thus confirming that postural control and visuospatial and non-spatial working memory share brain regions and compete with each other.

Elderly mice with history of acetaminophen intoxication display worsened cognitive impairment and persistent elevation of astrocyte and microglia burden

Acetaminophen (APAP) is a leading cause of acute liver failure. The effect of APAP metabolite’s effects in the periphery are well characterized; however, associated consequences in the brain remain poorly understood. Animal studies on this subject are few and reveal that frequent APAP intake can trigger cerebral abnormalities that vary depending on the subject’s age. Alarmingly, experimental efforts have yet to examine associated consequences in elderly hosts, who correspond to the highest risk of medication overload, impaired drug clearance, and cognitive deficits. Here, we interrogated the cerebral and peripheral pathology of elderly mice submitted to monthly episodes of APAP intoxication since a young adult age. We found that weeks after the final episode of recurrent APAP exposure, mice exhibited worsened non-spatial memory deficit whereas spatial memory performance was unaltered. Interestingly, one month after the period of APAP intoxication, these mice showed increased glial burden without associated drivers, namely, blood–brain barrier disruption, cholesterol accumulation, and elevation of inflammatory molecules in the brain and/or periphery. Our experimental study reveals how recurrent APAP exposure affects the cognitive performance and cellular events in elderly brains. These data suggest that APAP-containing pharmacological interventions may foreshadow the elevated risk of neuropsychiatric disorders that afflict elderly populations.

In-vivo evaluation of neuroprotective effect of Chinese plant calendula officinalis Linn. Flower Extract against Aluminium chloride-induced Alzheimer's in Wistar rats

ObjectiveTo investigate the neuroprotective properties of Calendula Officinalis Linn. flower extract (COE) against mild cognitive decline and cognitive dysfunction induced by aluminium chloride (AlCl3) in experimental rats. MethodologyCOE (100, 200, and 300 mg/kg p.o.) was given once daily following the treatment of AlCl3 (100 mg/kg p.o.) to male Wistar rats for 20 days. On the 1st, 10th, and 20th days, the walking track test, locomotor activity, and object recognition test were used as behaviour characteristics to assess spatial and non-spatial memory. On the 21st day, animals were sacrificed and brains removed for biochemical and histopathological analysis. ResultsCalendula officinalis Linn. extract significantly attenuated the AlCl3-induced alterations in body weight, and motor coordination such as locomotion, stride length, and object recognition parameters. COE also reduced oxidative stress by increasing GSH, catalase, SOD, and decreasing TBARS levels. Calendula officinalis Linn. extract high dose showed most prominent therapeutic effects. P < 0.05 and mean ± SD were used to compare mean values with normal control, disease control, and high doses of Calendula officinalis Linn. extract. DiscussionBased on our study, oxidative stress has been proposed as a mechanism for AlCl3-induced neurotoxicity. We conclude that Calendula officinalis Linn. flower extract substantially decreased oxidative stress and behavioural alterations in rats treated with aluminium chloride. Calendula officinalis flowers may provide significant neuroprotective effects, potentially improving memory and learning abilities. Calendula officinalis Linn flower extract contains anti-inflammatory and antioxidant effects that might be responsible for its neuroprotective properties.

Quercetin Inhibits Neuronal Pyroptosis and Ferroptosis by Modulating Microglial M1/M2 Polarization in Atherosclerosis.

Atherosclerosis (AS) with iron and lipid overload and systemic inflammation is a risk factor for Alzheimer's disease. M1 macrophage/microglia participate in neuronal pyroptosis and recently have been reported to be the ferroptosis-resistant phenotype. Quercetin plays a prominent role in preventing and treating neuroinflammation, but the protective mechanism against neurodegeneration caused by iron deposition is poorly understood. ApoE-/- mice were fed a high-fat diet with or without quercetin treatment. The Morris water maze and novel object recognition tests were conducted to assess spatial learning and memory, and nonspatial recognition memory, respectively. Prussian blue and immunofluorescence staining were performed to assess the iron levels in the whole brain and in microglia, microglia polarization, and the degree of microglia/neuron ferroptosis. In vitro, we further explored the molecular biological alterations associated with microglial polarization, neuronal pyroptosis, and ferroptosis via Western blot, flow cytometry, CCK8, LDH, propidium iodide, and coculture system. We found that quercetin improved brain lesions and spatial learning and memory in AS mice. Iron deposition in the whole brain or microglia was reversed by the quercetin treatment. In the AS group, the colocalization of iNOS with Iba1 was increased, which was reversed by quercetin. However, the colocalization of iNOS with PTGS2/TfR was not increased in the AS group, suggesting a character resisting ferroptosis. Quercetin induced the expression of Arg-1 and decreased the colocalizations of Arg-1 with PTGS2/TfR. In vitro, ox-LDL combined with ferric ammonium citrate treatment (OF) significantly shifted the microglial M1/M2 phenotype balance and increased the levels of free iron, ROS, and lipid peroxides, which was reversed by quercetin. M1 phenotype induced by OF caused neuronal pyroptosis and was promoted to ferroptosis by L-NIL treatment, which contributed to neuronal ferroptosis as well. However, quercetin induced the M1 to M2 phenotype and inhibited M2 macrophages/microglia and neuron pyroptosis or ferroptosis. In summary, quercetin alleviated neuroinflammation by inducing the M1 to M2 phenotype to inhibit neuronal pyroptosis and protected neurons from ferroptosis, which may provide a new idea for neuroinflammation prevention and treatment.

Nucleus accumbens core dopamine D2 receptors are required for performance of the odor span task in male rats.

The nucleus accumbens (NAc) core gates motivationally relevant behavioral action sequences through afferents from cortical and subcortical brain regions. While the role of the NAc core in reward and effort-based decision making is well established, its role in working memory (WM) processes is incompletely understood. The odor span task (OST) has been proposed as a measure of non-spatial working memory capacity (WMC) as it requires rodents to select a novel odor from an increasing number of familiar odors to obtain a food reward. To assess the role of the NAc core in the OST using (1) reversible chemical inactivation and (2) selective blockade of dopamine D1 and D2 receptors in the area. Well-trained male rats were tested on the OST following intra-NAc core infusions of muscimol/baclofen, the D1 receptorantagonist SCH-23390 (1 μg/hemisphere) and the D2 receptorantagonist eticlopride (1 μg/hemisphere). Behavioral measurements included the average odor span, maximum odor span, choice latency, searching vigor, and patterns of responding during foraging that may relate to impulsivity. Chemical inactivation of the NAc core significantly decreased odor span relative to sham and vehicle conditions. Selective antagonism of D2, but not D1, receptors in the NAc core also produced deficits in odor span. We found that secondary behavioral measures of choice latency, searching vigor, and responding to the first odor stimulus encountered were largely unaffected by treatment. These findings suggest that D2 receptors in the NAc core are required for OST performance.

Protective effects of Embelin in Benzo[α]pyrene induced cognitive and memory impairment in experimental model of mice

Alzheimer's disease (AD) is a neurodegenerative disease that affects the neurons in the hippocampus, resulting in cognitive and memory impairment. The most prominent clinical characteristics of AD are the production of amyloid-beta (Aβ) plaques, neurofibrillary tangles, and neuroinflammation in neurons. It has been proven that embelin (Emb) possesses antioxidant, anti-inflammatory, and neuroprotective properties. Therefore, we assessed the therapeutic potential of Emb in Benzo [α]pyrene (BaP)-induced cognitive impairment in experimental mice. BaP (5 mg/kg, i. p) was given to mice daily for 28 days, and Emb (2.5, 5, and 10 mg/kg, i. p) was given from 14 to 28 days of a protocol. In addition, locomotor activity was evaluated using open-field and spatial working, and non-spatial memory was evaluated using novel object recognition tasks (NORT), Morris water maze (MWM), and Y- maze. At the end of the study, the animal tissue homogenate was used to check biochemicals, neuroinflammation, and neurotransmitter changes. BaP-treated mice showed a significant decline in locomotor activity, learning and memory deficits and augmented oxidative stress (lipid peroxidation, nitrite, and GSH). Further, BaP promoted the release of inflammatory tissue markers, decreased acetylcholine, dopamine, GABA, serotonin, and norepinephrine, and increased glutamate concentration. However, treatment with Emb at dose-dependently prevented biochemical changes, improved antioxidant levels, reduced neuroinflammation, restored neurotransmitter concentration, and inhibited the NF-κB pathway. The current study's finding suggested that Emb improved cognitive functions through antioxidant, anti-inflammatory, and neuroprotective mechanisms and inhibition of acetylcholinesterase (AChE) enzyme activities and Aβ-42 accumulation.

Rotating magnetic field inhibits Aβ protein aggregation and alleviates cognitive impairment in Alzheimer's disease mice.

Amyloid beta (Aβ) monomers aggregate to form fibrils and amyloid plaques, which are critical mechanisms in the pathogenesis of Alzheimer's disease (AD). Given the important role of Aβ1-42 aggregation in plaque formation, leading to brain lesions and cognitive impairment, numerous studies have aimed to reduce Aβ aggregation and slow AD progression. The diphenylalanine (FF) sequence is critical for amyloid aggregation, and magnetic fields can affect peptide alignment due to the diamagnetic anisotropy of aromatic rings. In this study, we examined the effects of a moderate-intensity rotating magnetic field (RMF) on Aβ aggregation and AD pathogenesis. Results indicated that the RMF directly inhibited Aβ amyloid fibril formation and reduced Aβ-induced cytotoxicity in neural cells in vitro. Using the AD mouse model APP/PS1, RMF restored motor abilities to healthy control levels and significantly alleviated cognitive impairments, including exploration and spatial and non-spatial memory abilities. Tissue examinations demonstrated that RMF reduced amyloid plaque accumulation, attenuated microglial activation, and reduced oxidative stress in the APP/PS1 mouse brain. These findings suggest that RMF holds considerable potential as a non-invasive, high-penetration physical approach for AD treatment.

Antidepressant-Like Effects of Cinnamomum verum on Open-Space Forced Swim-Induced Depression in Mice.

Depression is a mental disorder characterized by depressive episodes, such as low mood, low self-esteem, feeling of guilt, and poor concentration. Depression has a high comorbidity with cognitive impairments. Studies have shown that cinnamon has anti-inflammatory antiviral, antihypertensive, antioxidant and anti-diabetic potentials. Therefore, the aim of the research was to assess the antidepressant effect of cinnamon on open-space forced swim-induced depression in mice. Twenty-five (25) Swiss albino mice were grouped into five groups (n=5). Group I: control (negative control) exposed to open-space forced swim test (OSFST) without any treatment, Groups II, III and IV received graded doses of Cinnamon 12.5, 25, and 50 mg/kg, group 5 (positive control) received fluoxetine 20 mg/kg orally. The animals were subjected to OSFST, Open Field Test (Line Crossing) and Novel Object Recognition Test (NORT). Administration of cinnamon showed decreased immobility time (behavioural despair) in OSFST compared to control and fluoxetine groups (p < 0.05). However, no statistically significant effect was observed in line crossing (locomotor activity) and the discrimination ratio of NORT (non-spatial short-term memory) between cinnamon administered groups and the control group. In conclusion, cinnamon has shown antidepressant-like effect in open-space forced swim-induced depression in mice. Keywords: Cinnamon, Depression, Cognitive impairment, Immobility time, Behavioural despair.

Diosmin alleviates doxorubicin-induced chemobrain in rats via inhibition of oxido-inflammation, apoptosis and modulation of autophagy

Background/aimDoxorubicin (DOX) is a highly effective chemotherapy medicine commonly used to treat breast cancer; yet, despite its clinical efficacy, it usually causes chemobrain. As a result, we investigated the neuroprotective effects of Diosmin (DIOS) on DOX-induced chemobrain in male rat brains. Animals and methodsIn the experimental protocol, Rats were divided into 4 groups: group I received solvent and saline for 56 days, group II received Dios and a concomitant dose of saline for 56 days, group III received DOX intraperitoneally on 7th, 14th, 21st, 28th, 35th, 42nd, 49th and 56th days, and Group IV received DIOS (40 mg/kg P.O.) for 56 days and DOX was administered one hour after DIOS oral administration. The novel-object recognition memory test (NORT) was used to assess non-spatial memory function. Following that, brain neurochemical status were assessed. ResultsDIOS increased cognitive performance in DOX-treated rats by enhancing exploration of unfamiliar objects. DIOS protects the brain from DOX-mediated alterations in oxidative status, as well as brain metabolic enzyme indicators. It also decreased MMP-6, IL-6, IL-β1, TNF-α and COX-2 expression, reduced apoptotic markers levels, boosted mTOR protein levels, lowered beclin-1, restored brain metabolic enzyme activities, increased neurotransmitter as well as cathepsin levels, and avoided the rise in α-synuclein and PON1 enzyme activity. ConclusionIn conclusion, DIOS protects rats' brains against DOX-induced chemobrain via oxidative stress inhibition, autophagy modulation, and down-regulation of inflammatory and apoptotic markers.

Chitosan/PLA-loaded Magnesium oxide nanocomposite to attenuate oxidative stress, neuroinflammation and neurotoxicity in rat models of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by amyloid-beta (Aβ) aggregation, neuroinflammation, oxidative stress, and dysfunction in the mitochondria and cholinergic system. In this study, the synthesis of chitosan-polylactic acid-loaded magnesium oxide nanocomposite (CH/PLA/MgONCs) was examined using the green precipitation method. The synthesized CH/PLA/MgONCs were confirmed by using the UV-Vis spectrum, FT-IR, SEM-EDAX, and physical properties. The experiments were carried out using male Wistar rats by injecting streptozotocin (STZ) bilaterally into the brain's ventricles through the intracerebroventricular (ICV) route at a dose of 3mg/kg. We also evaluated the effects of CH/PLA/MgONCs at doses of 10mg/kg. To assess the cognitive dysfunction induced by ICV-STZ, we performed behavioral, biochemical, and histopathological analyses. In our study results, UV-Vis spectrum analysis of CH/PLA/MgONCs showed 285nm, FT-IR analyses confirmed that the various functional groups were present, and SEM-EDAX analysis confirmed that a cauliflower-like spherical shape, Mg and O were present. Treatment with CH/PLA/MgONCs (10mg/kg) showed a significant improvement in spatial and non-spatial memory functions. This was further supported by biochemical analysis showing improved antioxidant enzyme (GSH, SOD, CAT, and GPx activity) activities that significantly attenuated cholinergic activity and oxidative stress. In the CH/PLA/MgONCs-treated group, significant improvement was observed in the mitochondrial complex activity. ICV-STZ-induced neuroinflammation, as indicated by increased levels of TNF-α, IL-6, and CRP, was significantly reduced by CH/PLA/MgONCs treatment. Additionally, CH/PLA/MgONCs treated histological results showed improved healthy neuronal cells in the brain. Furthermore, in silico studies confirm that these molecules have good binding affinity and inhibit Aβ aggregation. In conclusion, CH/PLA/MgONCs treatment reversed AD pathology by improving memory and reducing oxidative stress, neuroinflammation, and mitochondrial dysfunction. These findings recommend that CH/PLA/MgONCs are possible therapeutic agents to treat AD.

Mega-scale movie-fields in the mouse visuo-hippocampal network.

Natural visual experience involves a continuous series of related images while the subject is immobile. How does the cortico-hippocampal circuit process a visual episode? The hippocampus is crucial for episodic memory, but most rodent single unit studies require spatial exploration or active engagement. Hence, we investigated neural responses to a silent movie (Allen Brain Observatory) in head-fixed mice without any task or locomotion demands, or rewards. Surprisingly, a third (33%, 3379/10263) of hippocampal -dentate gyrus, CA3, CA1 and subiculum- neurons showed movie-selectivity, with elevated firing in specific movie sub-segments, termed movie-fields, similar to the vast majority of thalamo-cortical (LGN, V1, AM-PM) neurons (97%, 6554/6785). Movie-tuning remained intact in immobile or spontaneously running mice. Visual neurons had >5 movie-fields per cell, but only ~2 in hippocampus. The movie-field durations in all brain regions spanned an unprecedented 1000-fold range: from 0.02s to 20s, termed mega-scale coding. Yet, the total duration of all the movie-fields of a cell was comparable across neurons and brain regions. The hippocampal responses thus showed greater continuous-sequence encoding than visual areas, as evidenced by fewer and broader movie-fields than in visual areas. Consistently, repeated presentation of the movie images in a fixed, but scrambled sequence virtually abolished hippocampal but not visual-cortical selectivity. The preference for continuous, compared to scrambled sequence was eight-fold greater in hippocampal than visual areas, further supporting episodic-sequence encoding. Movies could thus provide a unified way to probe neural mechanisms of episodic information processing and memory, even in immobile subjects, across brain regions, and species.

A Review on the Disruption of Novel Object Recognition Induced by Methamphetamine.

Methamphetamine (MA), is a widely abused synthetic psychostimulant that leads to irreversible brain damage manifested as cognitive impairments in humans and animals. The novel object recognition (NOR) task is a commonly used behavioral assay for the investigation of non-spatial memory in rodents. This test is based on the natural tendency of rodents to spend more time exploring a novel object than a familiar one. NOR test has been used in many studies investigating cognitive deficits caused by MA in rodents. The objective of the present study was to review neurobiological mechanisms that might be responsible for MA-induced NOR alterations. A PubMed search showed 83 publications using novel object recognition and methamphetamine as keywords in the past 10 years. The present study revealed different MA regimens cause recognition memory impairment in rodents. In addition, it was found that the main neurobiological mechanism involved in MA-induced recognition deficits is the dysfunction of monoaminergic systems. NOR is a useful test to assess the cognitive functions following MA administration and evaluate the efficacy of new therapeutic agents in MA-addicted individuals.