scholarly journals Alpha-lipoic acid enhances short-term spatial memory of mice in open-space forced swim-induced depression mouse model

2021 ◽  
Vol 4 (3) ◽  
pp. 36-50
Author(s):  
Yusuf Yusha'u ◽  
Umar Muhammad Adam ◽  
Alhassan Abdul Wahab ◽  
Malajiya Ibrahim Alhaji Saleh ◽  
Jamilu Ya’u
Keyword(s):  
Object Recognition ◽  
Lipoic Acid ◽  
Normal Saline ◽  
Open Space ◽  
Novel Object Recognition ◽  
Alpha Lipoic Acid ◽  
Novel Object ◽  
Maze Test ◽  
Forced Swim ◽  
Y Maze

Depression affects over 264 million people of all ages globally. Major depressive disorder significantly and chronically reduced quality of life by its association with functional impairment both at home and in the workplace. Depressive patients consistently complain about cognitive disturbances, significantly exacerbating the burden of this illness. Several studies have shown that alpha-lipoic acid (ALA) possesses mitochondrial, antioxidant, anti-inflammatory and anti-diabetic properties, indicating a basis for evaluating the efficacy of ALA in depression. Hence, this research aimed to assess the possible anti-depressant effect of ALA in mice exposed to the open space forced swim test (OSFST) model of depression. Twenty-five (25) Swiss albino mice were grouped into five groups (n=5). Group 1: [Normal saline (NS)], Groups 2, 3 and 4 received graded doses of ALA 100, 200 and 400 mg/kg, respectively, Group 5 received fluoxetine 20 mg/kg orally. The animals were subjected to OSFST, novel object recognition test (NORT) and Y-maze test. Serotonin, brain-derived neurotrophic factor (BDNF), superoxide dismutase (SOD), malondialdehyde (MDA) and catalase levels of the mice were assessed. Treatment with ALA and fluoxetine significantly decreased immobility time compared to NS group in OSFST (p<0.05). Also, ALA at doses of 200 & 400 mg/kg and fluoxetine 20 mg/kg significantly increased spontaneous alternation ratio in the Y-maze test compared to the normal saline group (p<0.05), however, no significant difference was observed in novel object recognition using NORT between NS, ALA and fluoxetine treated groups. Similarly, the level of serotonin, SOD and catalase were not altered between the ALA and fluoxetine treated groups and NS group. In contrast, fluoxetine 20 mg/kg increased the brain BDNF level of the mice (p<0.05). Alpha-lipoic acid ameliorated depression in the OSFST murine model of depression and improved their cognition. Thus ALA can be a promising candidate in the development of novel anti-depressant medication.

scholarly journals Long-Term Changes in Cognition and Physiology after Low-Dose 16O Irradiation

2019 ◽  
Vol 20 (1) ◽  
pp. 188 ◽  
Author(s):  
Alexis Howe ◽  
Frederico Kiffer ◽  
Tyler C. Alexander ◽  
Vijayalakshmi Sridharan ◽  
Jing Wang ◽  
...  
Keyword(s):  
Object Recognition ◽  
Dentate Gyrus ◽  
National Laboratory ◽  
Space Radiation ◽  
High Energy ◽  
Galactic Cosmic Rays ◽  
High Mass ◽  
Novel Object Recognition ◽  
Novel Object ◽  
Y Maze

Astronauts traveling to Mars will be exposed to high levels of ionizing radiation upon leaving low-Earth orbit. During prolonged space travel, astronauts are exposed to galactic cosmic rays (GCRs) composed of protons; oxygen molecules; and high energy, high mass charged particles. Notably, oxygen molecules can travel through the shielding of spacecraft, potentially impacting 25% of the hippocampus. The aim of the current study was to assess whether 16O-particle radiation induced a behavioral deficit and histological changes in mice. Mice were sent to the National Aeronautics and Space Administration (NASA) Space Radiation Laboratory at Brookhaven National Laboratory and exposed to particulate 16O radiation at doses of 0 and 0.05 Gy. Nine months after irradiation, the mice were tested for novel object recognition and in the Y-maze, after which the animals were sacrificed. The brains were then dissected along the midsagittal plane for Golgi staining. Exposure to 0.05 Gy significantly impaired novel object recognition. However, short term memory and exploratory activity in the Y-maze were not affected. Micromorphometric analysis revealed significant decreases in mushroom spine density in the dentate gyrus and cornu Ammonis-1 and -3 of the hippocampus. Sholl analysis revealed a significant decrease in dendritic complexity in the dentate gyrus. The present data provide evidence that space radiation has deleterious effects on mature neurons associated with hippocampal learning and memory.

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 Alpha lipoic acid attenuated neuropathic pain induced by chronic constriction Injury of sciatic nerve in rats

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Prasad Neerati ◽  
Harika Prathapagiri
Keyword(s):  
Neuropathic Pain ◽  
Peripheral Neuropathy ◽  
Sciatic Nerve ◽  
Lipoic Acid ◽  
Normal Saline ◽  
Chronic Constriction Injury ◽  
Thermal Hyperalgesia ◽  
Alpha Lipoic Acid ◽  
Chronic Neuropathic Pain ◽  
Neuropathic Pain Syndrome

Abstract Background Chronic neuropathic pain syndrome is associated with impaired quality of life and is poorly manageable. Alpha lipoic acid (ALA) is a powerful antioxidant and showed its effectiveness on diabetic neuropathy and other acute peripheral nerve injuries but it was not evaluated in the chronic neuropathic pain, chronic constriction injury (CCI) in rat model by using duloxetine (DLX) as standard. Methodology The main objective of the study was to expedite ALA effect on chronic peripheral neuropathy induced by CCI of sciatic nerve in rats. In this study, male Wister rats were randomly divided into six groups (n = 8) including, normal saline, sham operated, surgery control, DLX 30mg/kg treated, ALA treated 25mg/kg, and ALA+DLX. The CCI of sciatic nerve was conducted on all animals except normal saline group and studied for 21 days (i.e. 14 days treatment period & 7 days treatment free period) by using different behavioral, biochemical and, histopathology studies. Results ALA showed minor but significant decrease of thermal hyperalgesia, cold allodynia, malondialdehyde (MDA), total protein, lipid peroxidation, and nitric oxide levels and significant increase of motor coordination, glutathione level and decreased axonal degeneration significantly. These effects sustained even during treatment free period. ALA enhanced the effect of DLX when given in combination by showing sustained effect. In conclusion, ALA acted as potent antioxidant may be this activity is responsible for the potent neuroprotective effect. Conclusion Hence, ALA attenuated the nueroinflammation mediated by chronic peripheral neuropathy. Further studies are warranted with ALA to develop as a clinically relevant therapeutic agent for the treatment of neuropathic pain.

scholarly journals Mice deficient in the NAAG synthetase II gene Rimkla are impaired in a novel object recognition task

2021 ◽  
Author(s):  
Ivonne Becker ◽  
Lihua Wang‐Eckhardt ◽  
Julia Lodder‐Gadaczek ◽  
Yong Wang ◽  
Agathe Grünewald ◽  
...  
Keyword(s):  
Object Recognition ◽  
Recognition Task ◽  
Novel Object Recognition ◽  
Novel Object ◽  
Object Recognition Task ◽  
Novel Object Recognition Task

scholarly journals Social Factors Influence Behavior in the Novel Object Recognition Task in a Mouse Model of Down Syndrome

2021 ◽  
Vol 15 ◽  
Author(s):  
Cesar Sierra ◽  
Ilario De Toma ◽  
Lorenzo Lo Cascio ◽  
Esteban Vegas ◽  
Mara Dierssen
Keyword(s):  
Down Syndrome ◽  
Object Recognition ◽  
Environmental Factors ◽  
Mouse Models ◽  
Recognition Task ◽  
Novel Object Recognition ◽  
The Novel ◽  
Wild Type ◽  
Male And Female ◽  
Novel Object

The use of mouse models has revolutionized the field of Down syndrome (DS), increasing our knowledge about neuropathology and helping to propose new therapies for cognitive impairment. However, concerns about the reproducibility of results in mice and their translatability to humans have become a major issue, and controlling for moderators of behavior is essential. Social and environmental factors, the experience of the researcher, and the sex and strain of the animals can all have effects on behavior, and their impact on DS mouse models has not been explored. Here we analyzed the influence of a number of social and environmental factors, usually not taken into consideration, on the behavior of male and female wild-type and trisomic mice (the Ts65Dn model) in one of the most used tests for proving drug effects on memory, the novel object recognition (NOR) test. Using principal component analysis and correlation matrices, we show that the ratio of trisomic mice in the cage, the experience of the experimenter, and the timing of the test have a differential impact on male and female and on wild-type and trisomic behavior. We conclude that although the NOR test is quite robust and less susceptible to environmental influences than expected, to obtain useful results, the phenotype expression must be contrasted against the influences of social and environmental factors.

scholarly journals Cbsoverdosage is necessary and sufficient to induce cognitive phenotypes in mouse models of Down syndrome and interacts genetically withDyrk1a

2018 ◽  
Author(s):  
Damien Marechal ◽  
Véronique Brault ◽  
Alice Leon ◽  
Dehren Martin ◽  
Patricia Lopes Pereira ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Object Recognition ◽  
Synaptic Transmission ◽  
Actin Cytoskeleton ◽  
Epistatic Interaction ◽  
Novel Object Recognition ◽  
The Novel ◽  
Novel Object ◽  
Cystathionine Beta Synthase ◽  
Necessary And Sufficient

ABSTRACTIdentifying dosage sensitive genes is a key to understand the mechanisms underlying intellectual disability in Down syndrome (DS). The Dp(17Abcg1-Cbs)1Yah DS mouse model (Dp1Yah) show cognitive phenotype and needs to be investigated to identify the main genetic driver. Here, we report that, in the Dp1Yah mice, 3 copies of the Cystathionine-beta-synthase gene (Cbs)are necessary to observe a deficit in the novel object recognition (NOR) paradigm. Moreover, the overexpression ofCbsalone is sufficient to induce NOR deficit. Accordingly targeting the overexpression of human CBS, specifically in Camk2a-expressing neurons, leads to impaired objects discrimination. Altogether this shows thatCbsoverdosage is involved in DS learning and memory phenotypes. In order to go further, we identified compounds that interfere with the phenotypical consequence of CBS overdosage in yeast. Pharmacological intervention in the Tg(CBS) with one selected compound restored memory in the novel object recognition. In addition, using a genetic approach, we demonstrated an epistatic interaction betweenCbsandDyrk1a, another human chromosome 21 gene encoding the dual-specificity tyrosine phosphorylation-regulated kinase 1a and an already known target for DS therapeutic intervention. Further analysis using proteomic approaches highlighted several pathways, including synaptic transmission, cell projection morphogenesis, and actin cytoskeleton, that are affected by DYRK1A and CBS overexpression. Overall we demonstrated that CBS overdosage underpins the DS-related recognition memory deficit and that bothCBSandDYRK1Ainteract to control accurate memory processes in DS. In addition, our study establishes CBS as an intervention point for treating intellectual deficiencies linked to DS.SIGNIFICANT STATEMENTHere, we investigated a region homologous to Hsa21 and located on mouse chromosome 17. We demonstrated using three independent genetic approaches that the overdosage of the Cystathionine-beta-synthase gene (Cbs) gene, encoded in the segment, is necessary and sufficient to induce deficit in novel object recognition (NR).In addition, we identified compounds that interfere with the phenotypical consequence of CBS overdosage in yeast and in mouse transgenic lines. Then we analyzed the relation between Cbs overdosage and the consequence of DYRK1a overexpression, a main driver of another region homologous to Hsa21 and we demonstrated that an epistatic interaction exist betweenCbsandDyrk1aaffecting different pathways, including synaptic transmission, cell projection morphogenesis, and actin cytoskeleton.

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