scholarly journals Loss of CRMP2 O-GlcNAcylation leads to reduced novel object recognition performance in mice

Open Biology ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 190192 ◽  
Author(s):  
Villo Muha ◽  
Ritchie Williamson ◽  
Rachel Hills ◽  
Alison D. McNeilly ◽  
Thomas G. McWilliams ◽  
...  
Keyword(s):  
Nervous System ◽  
Memory Impairment ◽  
Recognition Performance ◽  
Novel Object Recognition ◽  
Small Decrease ◽  
Post Translational Modification ◽  
Site Specific ◽  
Novel Object ◽  
Collapsin Response Mediator Protein ◽  
Mediator Protein

O-GlcNAcylation is an abundant post-translational modification in the nervous system, linked to both neurodevelopmental and neurodegenerative disease. However, the mechanistic links between these phenotypes and site-specific O-GlcNAcylation remain largely unexplored. Here, we show that Ser517 O-GlcNAcylation of the microtubule-binding protein Collapsin Response Mediator Protein-2 (CRMP2) increases with age. By generating and characterizing a Crmp2 S517A knock-in mouse model, we demonstrate that loss of O-GlcNAcylation leads to a small decrease in body weight and mild memory impairment, suggesting that Ser517 O-GlcNAcylation has a small but detectable impact on mouse physiology and cognitive function.

scholarly journals Improved neurocognitive performance in FIV infected cats following treatment with the p75 neurotrophin receptor ligand LM11A-31

2020 ◽  
Author(s):  
Jonathan E. Fogle ◽  
Lola Hudson ◽  
Andrea Thomson ◽  
Barbara Sherman ◽  
Margaret Gruen ◽  
...  
Keyword(s):  
Nervous System ◽  
Adverse Effects ◽  
Open Field ◽  
Neurotrophin Receptor ◽  
Novel Object Recognition ◽  
P75 Neurotrophin Receptor ◽  
Sensory Thresholds ◽  
Neuroprotective Effects ◽  
Novel Object ◽  
Beneficial Effects

AbstractHIV rapidly infects the central nervous system (CNS) and establishes a persistent viral reservoir within microglia, perivascular macrophages and astrocytes. Inefficient control of CNS viral replication by antiretroviral therapy results in chronic inflammation and progressive cognitive decline in up to 50% of infected individuals with no effective treatment options. Neurotrophin based therapies have excellent potential to stabilize and repair the nervous system. A novel non-peptide ligand, LM11A-31, that targets the p75 neurotrophin receptor (p75NTR) has been identified as a small bioavailable molecule capable of strong neuroprotection with minimal side effects. To evaluate the neuroprotective effects of LM11A-31 in a natural infection model, we treated cats chronically infected with feline immunodeficiency virus (FIV) with 13 mg/kg LM11A-31 twice daily over a period of 10 weeks and assessed effects on cognitive functions, open field behaviors, activity, sensory thresholds, plasma FIV, cerebrospinal fluid (CSF) FIV, peripheral blood mononuclear cell provirus, CD4 and CD8 cell counts and general physiology. Between 12 and 18 months post-inoculation, cats began to show signs of neural dysfunction in T maze testing and novel object recognition, which were prevented by LM11A-31 treatment. Anxiety-like behavior was reduced in the open field and no changes were seen in sensory thresholds. Systemic FIV titers were unaffected but treated cats exhibited a log drop in CSF FIV titers. No significant adverse effects were observed under all conditions. The data indicate that LM11A-31 is likely to be a potent adjunctive treatment for the control of neurodegeneration in HIV infected individuals.Author SummaryThere are no effective treatments to halt the progression of most neurodegenerative diseases including HIV-associated neurodegeneration. Neurotrophins have the potential to provide strong neuroprotection but it has been difficult to develop usable interventions. A new drug, LM11A-31, that targets the p75 neurotrophin receptor has been developed that provides potent neuroprotection, is orally bioavailable and has the potential to prevent disease progression. The current studies were designed to evaluate the effects of the compound in an animal model of active HIV infection in preparation for a human clinical trial. Treatment of chronically infected animals with LM11A-31 normalized deficits in T maze performance, novel object recognition and open field behavior with no measurable adverse effects. Potential adverse effects associated with natural neurotrophins such as changes in sensory perception and increased systemic viral burden were not observed. A decrease in CSF FIV titers and a slight improvement in the CD4:CD8 ratio suggested that LM11A-31 may have beneficial effects beyond the anticipated neuroprotective effects. These findings are similar to beneficial effects seen in other animal models of neurodegeneration and CNS injury and support the use of LM11A-31 as an adjunctive neuroprotective agent for the treatment of HIV infected individuals.

scholarly journals Temporal trajectories of novel object recognition performance in mice exposed to intermittent hypoxia

2017 ◽  
Vol 50 (6) ◽  
pp. 1701456 ◽  
Author(s):  
David Gozal ◽  
Abdelnaby Khalyfa ◽  
Zhuanghong Qiao ◽  
Isaac Almendros ◽  
Ramon Farré
Keyword(s):  
Object Recognition ◽  
Intermittent Hypoxia ◽  
Early Recognition ◽  
Recognition Performance ◽  
Sleep Apnoea ◽  
Novel Object Recognition ◽  
Neurocognitive Deficits ◽  
Performance Deficits ◽  
Novel Object ◽  
Resting Period

Intermittent hypoxia is one of the major perturbations of sleep-disordered breathing and has been causally implicated in neurocognitive deficits. However, the reversibility of such deficits is unclear.Male C57BL/6J mice were exposed to either intermittent hypoxia or room air for 3–240 days, and then half were randomly selected and allowed to recover in normoxic conditions for the same duration of the previous exposure. A novel object recognition (NOR) test was performed.NOR performance was stable over time in room air. Intermittent hypoxia induced significant reductions in recognition index that progressed over the first 45 days and stabilised thereafter. Normoxic recovery of recognition index was essentially complete and indistinguishable from room air in mice exposed to shorter intermittent hypoxia times (<90 days). However, significant residual deficits emerged after normoxic recovery following prolonged intermittent hypoxia exposures (p<0.01). In addition, gradual attenuation of the magnitude of recovery in recognition index occurred with increasingly longer intermittent hypoxia exposures (MANOVA p<0.0001).Intermittent hypoxia during the resting period reduces NOR performance in a time-dependent fashion. Reversal of NOR performance deficits is unlikely after prolonged intermittent hypoxia duration. These findings suggest that early recognition of sleep apnoea and effective treatment are critical for restoration of the adverse cognitive effects of the disease.

scholarly journals Antiamnesic Effects of a Hydroethanolic Extract of Crinum macowanii on Scopolamine-Induced Memory Impairment in Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Andrew T. Mugwagwa ◽  
Louis L. Gadaga ◽  
William Pote ◽  
Dexter Tagwireyi
Keyword(s):  
Object Recognition ◽  
Memory Impairment ◽  
Positive Control ◽  
Novel Object Recognition ◽  
Significant Activity ◽  
Novel Object ◽  
Y Maze ◽  
Hydroethanolic Extract ◽  
Dose Dependent Increase ◽  
Dose Dependent

Crinum macowanii has been found to contain alkaloids that have activity against acetylcholinesterase enzyme in vitro. The present study was undertaken to investigate the in vivo ability of hydroethanolic crude extract of Crinum macowanii to ameliorate memory impairment induced by scopolamine. Thirty-six male Balb/c mice weighing around 25–35 g were employed in the present investigation. Y-maze and novel object recognition apparatus served as the exteroceptive behavioural models, and scopolamine-induced amnesia served as the interoceptive behavioural model. C. macowanii (10, 20, and 40 mg/kg p.o.) was administered in single doses to the mice. Donepezil (3 mg/kg p.o.) was used as a positive control agent. C. macowanii extract reversed the amnesia induced by scopolamine as indicated by a dose-dependent increase in spontaneous alternation performance in the Y-maze task. C. macowanii 40 mg/kg showed significant activity (p<0.05 versus negative control), comparable to that of the positive control. C. macowanii also showed memory-enhancing activity against scopolamine-induced memory deficits in the long-term memory novel object recognition performance as indicated by a dose-dependent increase in the discrimination index. The results indicate that the hydroethanolic extract of C. macowanii may be a useful memory restorative mediator in the treatment of cognitive disorders such as Alzheimer’s disease.

scholarly journals GLP-1R Activation Ameliorate Novel-object Recognition Function via Hippocampal AMPK/NF-κB Signaling Pathway in Neuropathic Pain Mice

2020 ◽  
Author(s):  
Long-Qing Zhang ◽  
Wen Zhang ◽  
Ting Li ◽  
Ting Yang ◽  
Xiaoman Yuan ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Object Recognition ◽  
Recognition Memory ◽  
Signaling Pathway ◽  
Memory Impairment ◽  
Novel Object Recognition ◽  
Novel Object ◽  
Compound C ◽  
Associated Proteins ◽  
With Memory

Abstract Background: Growing evidences indicate that neuropathic pain is frequently accompanied with cognitive impairments, which aggravate the decrease in the quality of life of chronic pain patients. Furthermore, it has been shown that the activation of Glucagon-like-peptide-1receptor (GLP-1R) improved memory deficit in multiple diseases such as Alzheimer’s disease (AD), stroke and so on. However, whether activating GLP-1R could improve memory impairment induced by neuropathic pain and the mechanism by which this improvement would occur remain unclear. Methods: The spared nerve injury (SNI) model was established as a kind of neuropathic pain. And novel-object recognition memory (hippocampus-dependent memory) was tested by the novel object recognition test (NORT).The expression levels of GLP-1,GLP-1R,adenosine monophosphate-activated protein kinase (AMPK),p-AMPKThr172, nuclear factor κ B p65 (NF-κB p65), interleukin-1β p17(IL-1β p17),and the synaptic associated proteins were tested in the murine hippocampus with memory deficits caused by neuropathic pain. Then, exenatide acetate (Ex-4, a GLP-1R agonist), exendin(9-39)(Ex(9-39),a GLP-1R antagonist) and Compound C dihydrochloride ( CC, an AMPK inhibitor) were used to test the effects of activating GLP-1R in mice with neuropathic pain.Results: First, we uncovered that neuropathic pain could inhibit GLP-1/GLP-R axis, disturb inflammatory signaling pathway, increase the expression of IL-1β and downregulate the synaptic associated proteins (postsynaptic density protein 95(PSD95) and Arc). Subsequently, we reported that Ex-4 treatment could improve recognition memory impairment and increase the ratio of p-AMPKThr172/AMPK, decrease the expression of NF-κB p65 and IL-1β p17, upregulate the levels of PSD95 and Arc. Moreover, we uncovered that Ex(9-39) and CC treatment could abrogate the neuroprotection of Ex-4 in mice with memory impairment induced by neuropathic pain.Conclusions: The results indicated that the activation of GLP-1R could improve recognition memory impairment caused by neuropathic pain via activating AMPK signaling pathway, then, which could inhibit NF-κB activating and its downstream IL-1β expression, upregulate the levels of PSD95 and Arc proteins.

scholarly journals Scopolamine-Induced Memory Impairment in Mice: Neuroprotective Effects of Carissa edulis (Forssk.) Valh (Apocynaceae) Aqueous Extract

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Fanta Sabine Adeline Yadang ◽  
Yvette Nguezeye ◽  
Christelle Wayoue Kom ◽  
Patrick Herve Diboue Betote ◽  
Amina Mamat ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Aqueous Extract ◽  
Cholinergic System ◽  
Memory Impairment ◽  
Ache Activity ◽  
Novel Object Recognition ◽  
Novel Object ◽  
Central Cholinergic System

Alzheimer’s disease is first characterised by memory loss related to the central cholinergic system alteration. Available drugs provide symptomatic treatment with known side effects. The present study is aimed to evaluate the properties of Carissa edulis aqueous extract on a Scopolamine mouse model as an attempt to search for new compounds against Alzheimer’s disease-related memory impairment. Memory impairment was induced by administration of 1 mg/kg (i.p.) of Scopolamine for 7 days, and mice were treated with Carissa edulis aqueous extract. Behavioural studies were performed using T-maze and novel object recognition task for assessing learning and memory and open field test for locomotion. Brain acetylcholinesterase enzyme (AChE) activity was measured to evaluate the central cholinergic system. The level of MDA, glutathione, and catalase activity were measured to evaluate the oxidative stress level. Administration of Scopolamine shows a decrease in learning and memory enhancement during behavioural studies. A significant decrease in the time spent in the preferred arm of T-maze, in the time spent in the exploration of the novel object, and in the discrimination index of the familiar object was also observed. The significant impairment of the central cholinergic system was characterised in mice by an increase of AChE activity to 2.55±0.10 mol/min/g with an increase in oxidative stress. Treatment with the different doses of Carissa edulis (62.8, 157, 314, and 628 mg/kg orally administrated) significantly increased the memory of mice in T-maze and novel object recognition tests and also ameliorated locomotion of mice in the open field. Carissa edulis aqueous extract treatment also decreases the AChE activity and brain oxidative stress. It is concluded that administration of Carissa edulis aqueous extract enhances memory of mice by reducing AChE activity and demonstrating antioxidant properties. This could be developed into a novel therapy against memory impairment related to Alzheimer’s disease.

scholarly journals Diosmetin Mitigates Cognitive and Memory Impairment Provoked by Chronic Unpredictable Mild Stress in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Elham Saghaei ◽  
Shakiba Nasiri Boroujeni ◽  
Parvin Safavi ◽  
Zeinab Borjian Boroujeni ◽  
Elham Bijad
Keyword(s):  
Object Recognition ◽  
Antioxidant Capacity ◽  
Chronic Stress ◽  
Memory Impairment ◽  
Control Group ◽  
Novel Object Recognition ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Novel Object ◽  
Serum Corticosterone

Background and Aim. Numerous reports have indicated that dealing with stressors in life is a main risk factor for the occurrence and progression of cognitive and memory impairment. Available treatments such as benzodiazepine and antidepressants address only certain aspects of this stress disorder and have numerous side effects. The present study was aimed at investigating the effect of diosmetin, as a flavonoid compound with potent antioxidant and anti-inflammatory effects, on cognitive impairment and chronic stress memory. Materials and Methods. In the present experimental study, male NMRI mice were exposed to chronic unpredictable mild stress (CUMS) paradigm for 35 days. Diosmetin (at doses of 10, 20, and 40 mg/kg. i.p.) or diosmetin solvent (normal saline + DMSO, 1 ml/kg; i.p.) was administered 30 min before stress induction. After 28 days, memory and cognitive performance were assessed by shuttle box and novel object recognition tests. Finally, antioxidant capacity (FRAP) and malondialdehyde (MDA) level of serum and brain, and serum corticosterone level were evaluated. Results. Behavioral tests showed that CUMS significantly reduced the secondary latency in passive avoidance memory test and diagnosis index in novel object recognition test compared to the control group ( P < 0.001 ), whereas treatment with diosmetin (20 and 40 mg/kg) significantly improved memory performance in the two tests ( P < 0.001 ). In addition, diosmetin (40 mg/kg) could pronouncedly suppress increase in serum corticosterone levels, reduction in antioxidant capacity, and production of excess MDA caused by CUMS compared to the control group ( P < 0.01 , P < 0.001 , and P < 0.001 , respectively). Conclusion. Chronic stress can impair memory and cognition and treatment with diosmetin can partly improve this disorder in male mice by increasing the antioxidant capacity of brain tissue and serum and improving serum corticosterone levels.

scholarly journals Cognitive-Enhancing Effect of a Hydroethanolic Extract of Crinum macowanii against Memory Impairment Induced by Aluminum Chloride in BALB/c Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-10
Author(s):  
Mohammed S. Jilani ◽  
Dexter Tagwireyi ◽  
Louis L. Gadaga ◽  
Charles C. Maponga ◽  
Cosmas Mutsimhu
Keyword(s):  
Aluminum Chloride ◽  
Water Maze ◽  
Memory Impairment ◽  
Recognition Task ◽  
Novel Object Recognition ◽  
The Novel ◽  
Novel Object ◽  
Object Recognition Task ◽  
Novel Object Recognition Task ◽  
Hydroethanolic Extract

Crinum macowanii is a bulbous plant indigenous to many parts of Southern Africa. Extracts of C. macowanii have gained interest since the discovery of various alkaloids, few of which possess acetylcholinesterase inhibitory activity. The present study was performed to evaluate the effect of a crude hydroethanolic extract of C. macowanii against aluminum chloride-induced memory impairment in mice using the Morris water maze and the novel object recognition task. C. macowanii (10, 20, and 40 mg/kg p.o) was administered daily for five weeks, while donepezil (3 mg/kg p.o) was used as the positive control. C. macowanii at a dosage of 40 mg/kg showed a significantly lower escape latency than the negative control (P<0.0001) and was found to be comparable to donepezil 3 mg/kg in the Morris water maze test. C. macowanii at 40 mg/kg exhibited a significantly higher discrimination index than aluminum chloride-treated mice in the novel object recognition task. The results may support the usefulness of C. macowanii in the management of dementia and related illnesses.

scholarly journals Modification of NO-cGMP Pathway Differentially Affects Diazepam- and Flunitrazepam-Induced Spatial and Recognition Memory Impairments in Rodents

2019 ◽  
Vol 37 (4) ◽  
pp. 1036-1046 ◽  
Author(s):  
Jolanta Orzelska-Górka ◽  
Piotr Bernat ◽  
Piotr Tutka ◽  
Joanna Listos ◽  
Ewa Kędzierska ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Recognition Memory ◽  
Animal Behavior ◽  
Memory Impairment ◽  
Elevated Plus Maze ◽  
Novel Object Recognition ◽  
Novel Object ◽  
Memory Impairments ◽  
Plus Maze ◽  
Cgmp Pathway

AbstractThis study investigated the influence of sildenafil and methylene blue (MB), two modulators of the nitric oxide (NO)-cyclic guanosine-3′,5′-monophosphate (cGMP) pathway on amnesic effects of two benzodiazepines (BZs) (diazepam (DZ) and flunitrazepam (FNZ)), in rodents—mice and rats. In the modified elevated plus maze (mEPM) and novel object recognition (NOR) tests, MB given ip at a dose of 5 mg/kg 5 min prior to DZ administration (0.25 or 1 mg/kg, sc) enhanced/induced memory impairment caused by DZ. When MB (2.5, 5, and 10 mg/kg) was applied 5 min prior to FNZ administration (0.05 and 0.1 mg/kg), an effect was opposite and memory impairment induced by FNZ was reduced. When sildenafil (2.5 and 5 mg/kg, ip) was applied 5 min prior to DZ, we observed a reduction of DZ-induced memory deficiency in the mEPM test. A similar effect of sildenafil was shown in the NOR test when the drug was applied at doses of 1.25, 2.5, and 5 mg/kg prior to DZ. In the mEPM test, sildenafil at abovementioned doses had no effects on FNZ-induced memory impairment. In turns, sildenafil administered at doses of 2.5 and 5 mg/kg increased the effect of FNZ on memory impairment in the NOR test. In conclusion, the NO-cGMP pathway is involved differentially into BZs-induced spatial and recognition memory impairments assessed using the NOR and mEPM tests. Modulators of the NO-cGMP pathway affect animal behavior in these tests in a different way depending on what benzodiazepine is applied.

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