scholarly journals The Effects of 5-Fluorouracil/Leucovorin Chemotherapy on Cognitive Function in Male Mice

2021 ◽  
Vol 8 ◽  
Author(s):  
Thomas Groves ◽  
Christa Corley ◽  
Stephanie D. Byrum ◽  
Antiño R. Allen
Keyword(s):  
Spatial Memory ◽  
Probe Trial ◽  
Water Maze ◽  
Memory Retention ◽  
Male Mice ◽  
Vessel Morphology ◽  
Tandem Mass Tag ◽  
Y Maze ◽  
Plus Maze ◽  
Significant Impairment

5-Fluorouracil (5-Fu) and leucovorin (LV) are often given in combination to treat colorectal cancer. 5-Fu/LV prevents cell proliferation by inhibiting thymidylate synthase, which catalyzes the conversion of deoxyuridine monophosphate to deoxythymidine monophosphate. While 5-Fu has been shown to cause cognitive impairment, the synergistic effect of 5-Fu with LV has not been fully explored. The present investigation was designed to assess how the combination of 5-Fu and LV affect cognition in a murine model. Six-month-old male mice were used in this study; 15 mice received saline injections and 15 mice received 5-Fu/LV injections. One month after treatment, the elevated plus maze, Y-maze, and Morris water maze behavioral tasks were performed. Brains were then extracted, cryosectioned, and stained for CD68 to assay microglial activation and with tomato lectin to assay the vasculature. All animals were able to locate the visible and hidden platform locations in the water maze. However, a significant impairment in spatial memory retention was observed in the probe trial after the first day of hidden-platform training (first probe trial) in animals that received 5-Fu/LV, but these animals showed spatial memory retention by day 5. There were no significant increases in inflammation as measured by CD68, but 5-Fu/LV treatment did modulate blood vessel morphology. Tandem mass tag proteomics analysis identified 6,049 proteins, 7 of which were differentially expressed with a p-value of <0.05 and a fold change of >1.5. The present data demonstrate that 5-Fu/LV increases anxiety and significantly impairs spatial memory retention.

Behavioral and molecular effects of intrahippocampal infusion of auraptene, resveratrol, and curcumin on H-89-induced deficits on spatial memory acquisition and retention in Morris water maze

2019 ◽  
Vol 38 (7) ◽  
pp. 775-784 ◽  
Author(s):  
K Tabrizian ◽  
SS Musavi ◽  
M Rigi ◽  
F Hosseindadi ◽  
S Kordi ◽  
...  
Keyword(s):  
Spatial Memory ◽  
Morris Water Maze ◽  
Water Maze ◽  
Training Trial ◽  
Camp Response Element Binding ◽  
Memory Retention ◽  
Camp Response Element ◽  
Significant Impairment ◽  
Memory Acquisition ◽  
Molecular Effects

Our aim was to investigate the effects of resveratrol, auraptene, and curcumin on the spatial learning and spatial memory retention in the Morris water maze (MWM). The effects of 4-day bilateral intrahippocampal (i.h.) infusions of dimethyl sulfoxide (DMSO), H-89 as a protein kinase AII inhibitor, auraptene/H-89, resveratrol/H-89, and curcumin/H-89 were investigated on spatial memory acquisition in MWM. The rats were trained for 4 days; each day included one block of four trials. Post-training probe tests were performed on day 5 in acquisition test. For retention assessments, different animals were trained for 4 days and then infused (i.h.) with either DMSO, H-89, auraptene/H-89, resveratrol/H-89, or curcumin/H-89. The retention test was performed 48 h after the last training trial. The bilateral infusion of H-89 led to a significant impairment in spatial memory in acquisition and retention tests accompanied with a significant decrease in expressions of cAMP response-element binding (CREB) and pCREB proteins in hippocampus. Resveratrol and curcumin reversed the H-89-induced spatial memory acquisition and retention impairments with significant increases in both CREB and pCREB proteins expressions compared to H-89-treated animals. Auraptene showed significant effects in reversing H-89-induced impairments in spatial memory retention but not spatial memory acquisition.

scholarly journals Subchronic Oral Bromocriptine Methanesulfonate Enhances Open Field Novelty-Induced Behavior and Spatial Memory in Male Swiss Albino Mice

2013 ◽  
Vol 2013 ◽  
pp. 1-5
Author(s):  
Olakunle James Onaolapo ◽  
Adejoke Yetunde Onaolapo
Keyword(s):  
Spatial Memory ◽  
Open Field ◽  
Cumulative Effect ◽  
Male Mice ◽  
Healthy Male ◽  
Swiss Albino Mice ◽  
Y Maze ◽  
Field Assessment ◽  
Albino Mice ◽  
Neurobehavioral Effects

This study set out to assess the neurobehavioral effects of subchronic, oral bromocriptine methanesulfonate using the open field and the Y-maze in healthy male mice. Sixty adult Swiss albino mice were assigned into three groups. Controls received normal saline, while test groups received bromocriptine methanesulfonate at 2.5 and 5 mg/kg/day, respectively, for a period of 21 days. Neurobehavioral tests were carried out on days 1 and 21 after administration. Open field assessment on day 1 after administration revealed significant increase in grooming at 2.5 and 5 mg/kg, while horizontal and vertical locomotion showed no significant changes. Day 1 also showed no significant changes in Y-maze alternation. On day 21, horizontal locomotion, rearing, and grooming were increased significantly at 2.5 and 5 mg/kg doses after administration; also, spatial memory was significantly enhanced at 2.5 mg/kg. In conclusion, the study demonstrates the ability of oral bromocriptine to affect neurobehavior in normal mice. It also suggests that there is a cumulative effect of oral bromocriptine on the behaviors studied with more changes being seen after subchronic administration rather than after a single oral dose.

scholarly journals Memory Enhancing Activity of Ethanolic Extract of Delonix regia Leaves against Scopolamine induced Amnesia in Swiss Albino Mice

2021 ◽  
Vol 68 (1) ◽  
Author(s):  
Suwathi Ravichandar ◽  
K.A.S. Mohammed Shafeeq ◽  
S. Karpagam Kumara Sundari ◽  
R. Senthamarai
Keyword(s):  
Morris Water Maze ◽  
Water Maze ◽  
Elevated Plus Maze ◽  
Ethanolic Extract ◽  
Swiss Albino Mice ◽  
Delonix Regia ◽  
Y Maze ◽  
Plus Maze ◽  
Dose Levels ◽  
Memory Enhancing

In traditional system of medicine, various parts of Delonix regia have been used for many ailments. The objective of the present study was to evaluate the memory enhancing activity of Ethanolic Extract of Delonix regia leaves (EEDRL) against scopolamine induced amnesia by using Elevated Plus Maze, Y Maze and Morris Water Maze Models. Ethanolic Extract of Delonix regia was prepared then subjected to phytochemical analysis revealed the presence of flavonoids, alkaloids, carbohydrates, tannins, steroids, terpenoids, phenols and saponins. Acute oral toxicity was performed as per OECD guidelines 423. Based on this, two dose levels of EEDRL were chosen as 200 mg/kg and 400 mg/kg for pharmacological screening. Swiss albino mice were divided into five groups of six animals each. EEDRL at a dose levels 200 mg/kg & 400 mg/kg showed increase in inflexion ratio in Elevated Plus Maze, increase in Percentage alterations in Y Maze & decrease in Escape latency in Morris Water Maze Model compared to disease control in dose dependent manner which indicates that the EEDRL reverses the scopolamine induced amnesia in mice. The memory enhancing activity in mice might be due to facilitation of cholinergic transmission. Hence it can be concluded that Delonix regia appears to be a promising candidate for improving memory, and it would be worthwhile to explore the potential of this plant in the management of Alzheimer patient.

scholarly journals The ApoE-dependent Neuroprotective Effects of Sesamol on Diet-induced Obese Mice: The Role of Gut Microbiota and SCFAs (P06-049-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Tian Yuan ◽  
Zhigang Liu ◽  
Xuebo Liu
Keyword(s):  
Fatty Acids ◽  
Cognitive Deficits ◽  
Water Maze ◽  
Elevated Plus Maze ◽  
Short Chain Fatty Acids ◽  
Microbial Metabolites ◽  
Neuroprotective Effects ◽  
Y Maze ◽  
Plus Maze ◽  
Synapse Ultrastructure

Abstract Objectives Sesamol, an antioxidant lignan from sesame oil, possesses lipid lowering and neuroprotective bioactivities. Considering the distribution of sesamol in gut is much higher than brain after administration, the present work was aimed to elucidate the systemic protective effects of sesamol on dietary-induced cognitive deficits, and to determine the possible link between gut and brain. Methods Both wildtype and ApoE-/- mice were fed with high-fat diet (HFD) and treated with sesamol (0.05%, w/v) in drinking water for 10 weeks. The cognitive and anxiety behavioral assessment were evaluated by Morris-water maze, Y-maze, and elevated plus maze tests. The synapse ultrastructure was also detected by transmission electron microscope. Moreover, the alteration of gut microbiome and microbial metabolites short chain fatty acids (SCFAs) were also determined by 16S rDNA sequencing and GC, respectively. Results Sesamol prevented HFD-induced bodyweight gain, insulin resistance, and hyperlipidemia. However, the behavioral tests including Morris-water maze, Y-maze, and elevated plus maze tests indicated that sesamol could only improve cognitive deficits and anxiety behaviors in wildtype but not ApoE deficient mice. Consistently, sesamol improved synapse ultrastructure and inhibited brain Aβ accumulation in brain in an ApoE-dependent manner. Moreover, sesamol prevented HFD-induced gut barrier damages and systemic inflammation. Sesamol also re-shaped gut microbiome and consequently improved the generation of microbial metabolites short chain fatty acids including acetate, propionate, and butyrate. Conclusions To summarized, this study revealed that the possible mechanism of neuroprotective effects of sesamol might be ApoE-dependent, and the beneficial effects of sesamol on gut microbiota/metabolites could be translated into metabolic and neurodegenerative diseases treatment. Funding Sources This work was financially supported by the National Key Research and Development Program of China, National Natural Science Foundation of China. Supporting Tables, Images and/or Graphs

scholarly journals Amelioration of Scopolamine-Induced Amnesic, Anxiolytic and Antidepressant Effects of Ficus benghalensis in Behavioral Experimental Models

Medicina ◽  
2020 ◽  
Vol 56 (3) ◽  
pp. 144
Author(s):  
Humna Malik ◽  
Sana Javaid ◽  
Muhammad Fawad Rasool ◽  
Noreen Samad ◽  
Syed Rizwan Ahamad ◽  
...  
Keyword(s):  
Passive Avoidance ◽  
Open Field ◽  
Morris Water Maze ◽  
Water Maze ◽  
Elevated Plus Maze ◽  
Methanolic Extract ◽  
Ficus Benghalensis ◽  
Y Maze ◽  
Plus Maze ◽  
Phytochemical Studies

Background and Objectives: Ficus benghalensis (FB) is a commonly found tree in Pakistan and its various parts have folkloric importance in managing neurological ailments. In the present study, methanolic extract of its bark has been tested on an experimental animal model to evaluate memory-enhancing, anxiolytic and antidepressant activities to validate the claimed therapeutic potential. Materials and Methods: Methanolic extract of freshly isolated bark was prepared and subjected to preliminary phytochemical studies and gas chromatography–mass spectrometry (GC–MS) analysis for the presence of phytocomponents. To evaluate its effect on spatial learning, passive-avoidance test–step through (PAT-ST), Y-maze and Morris water maze (MWM) tests were carried out. Open-field (OFT) and elevated plus maze (EPM) tests were employed to explore the anti-anxiety potential of FB while a forced swimming test (FST) was utilized to assess its anti-depressant prospective. FB doses of 100, 200 and 300 mg/kg with positive and negative controls given to Sprague Dawley (SD) rats. Results: phytochemical studies showed the presence of various phytoconstituents including alkaloids, flavonoids, terpenes, phenolics and anthraquinones. The presence of synephrine, aspargine, glucose, fructose and fatty acids was revealed by GC–MS analysis. FB administration led to significant improved memory retention when evaluated through passive avoidance (p < 0.05), Y-maze (p < 0.05) and Morris water maze (p < 0.05) tests in a scopolamine model of amnesic rats. When tested by open field and elevated plus maze tests, FB demonstrated anxiety-resolving characteristics (p < 0.05) as animals dared to stay in open areas more than a control group. Mobility time was increased and immobility time was reduced (p < 0.05–0.01) in rats treated with FB, unveiling the anti-depressant importance of F. benghalensis. Conclusion: methanolic extract of F. benghalensis bark furnished scientific proof behind folkloric claims of the memory improving, anxiety-reducing and depression-resolving characteristics of the plant. These activities might be possible due to interaction of its phytoconstituents with serotonergic, glutamatergic, cholinergic and GABAergic systems in the brain.

scholarly journals The effects of the administration of two different doses of manganese on short-term spatial memory and anxiety-like behavior in rats

2011 ◽  
Vol 63 (4) ◽  
pp. 1031-1036 ◽  
Author(s):  
M. Hogas ◽  
A. Ciobica ◽  
Simona Hogas ◽  
Veronica Bild ◽  
L. Hritcu
Keyword(s):  
Spatial Memory ◽  
Wistar Rats ◽  
Elevated Plus Maze ◽  
Psychomotor Development ◽  
Short Term ◽  
Maze Task ◽  
Manganese Exposure ◽  
Y Maze ◽  
Plus Maze ◽  
Different Doses

Manganese is a very well known neurotoxic agent. It has been mainly linked to impaired motor skills and disturbed psychomotor development. However, very few aspects are known about the cognitive deficits and behavioral consequences of chronic manganese exposure. In this context, we report herein our findings regarding short-term spatial memory, motor and anxiety-like behavior assessments in male Wistar rats exposed for 45 days to two different doses (3 mg/kg b.w., i.p. and 10 mg/kg b.w., i.p.) of manganese. Behavior testing (Y-maze task and elevated plus maze) was performed after 45 days of manganese administration. Chronic manganese exposure in Wistar rats led to behavioral alterations consisting of cognitive deficiencies in the Y-maze task and anxiety/compulsive-like behaviors in the elevated plus maze, but no motor disturbances as tested by the number of arm entries in the Y-maze. Additional work is necessary to understand the longterm effects of different doses and dosing regimens of manganese on cognitive/affective and motor functioning.

scholarly journals Enhancing Spatial Memory: Anxiolytic and Antidepressant Effects ofTapinanthus dodoneifolius(DC) Danser in Mice

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Foyet Harquin Simplice ◽  
Tsala David Emery ◽  
Ngatanko Abaissou Hervé Hervé
Keyword(s):  
Spatial Memory ◽  
Open Field ◽  
Elevated Plus Maze ◽  
Behavioral Pattern ◽  
Forced Swimming ◽  
Y Maze ◽  
Plus Maze ◽  
Antidepressant Effects ◽  
Immobility Time ◽  
Sedative Activity

We evaluated the anxiolytic and antidepressant effects of the aqueous extract of the bark ofTapinanthus dodoneifolius(TAE) (Danser) (25, 50, and 100 mg/kg), using open field, elevated plus maze, and forced swimming tests. Effect of TAE was compared to standard drugs diazepam (2 mg/kg) and imipramine (10 mg/kg). Additionally, the same doses of TAE were evaluated on rat's memory using Y-maze task. Results showed a significant (P<0.05; 100 mg/kg) increase in the percentage of open arm entry and the time spent in the open arms in the elevated plus maze, suggesting an anxiolytic activity of the extract. In a dose-dependant manner, TAE at 25 mg/kg significantly (P<0.05) decreased the number of lines crossed and the rearing behavior in the open field test, suggesting its possible sedative activity. In the forced swimming test, the immobility time of the animal was significantly reduced (P<0.05) by TAE (100 mg/kg), compared to control, and this effect was quite comparable to that of imipramine. In the Y-maze paradigm, TAE at 50 mg/kg caused a significant increase in the spontaneous alternations but with a significant decrease in exploratory behavioral pattern. Taking these results together, TAE improved the spatial memory and showed anxiolytic, antidepressant, and sedative activities. The present results support the anxiolytic and antidepressant activities of TAE and, to our knowledge, for the first time, demonstrate its enhancing effect on memory.

scholarly journals Prenatal Methamphetamine Exposure Induces Long-Lasting Alterations in Memory and Development of NMDA Receptors in the Hippocampus

2014 ◽  
pp. S547-S558 ◽  
Author(s):  
R. ŠLAMBEROVÁ ◽  
M. VRAJOVÁ ◽  
B. SCHUTOVÁ ◽  
M. MERTLOVÁ ◽  
E. MACÚCHOVÁ ◽  
...  
Keyword(s):  
Spatial Memory ◽  
Nmda Receptors ◽  
Water Maze ◽  
The Other ◽  
Male Rats ◽  
Memory Retention ◽  
Prenatally Exposed ◽  
Object Recognition Test ◽  
Close Relationship

Since close relationship was shown between drug addiction and memory formation, the aim of the present study was to investigate the effects of interaction between prenatal methamphetamine (MA) exposure and MA treatment in adulthood on spatial and non-spatial memory and on the structure of the N-methyl-D-aspartate (NMDA) receptors in the hippocampus. Adult male rats prenatally exposed to MA (5 mg/kg) or saline were tested in adulthood. Non-spatial memory was examined in the Object Recognition Test (ORT) and spatial memory in the Object Location Test (OLT) and in the Memory Retention Test (MRT) conducted in the Morris Water Maze (MWM), respectively. Based on the type of the memory test animals were injected either acutely (ORT, OLT) or long-term (MWM) with MA (1 mg/kg). After each testing, animals were sacrificed and brains were removed. The hippocampus was then examined in Western Blot analysis for occurrence of different NMDA receptors’ subtypes. Our results demonstrated that prenatal MA exposure affects the development of the NMDA receptors in the hippocampus that might correspond with improvement of spatial memory tested in adulthood in the MWM. On the other hand, the effect of prenatal MA exposure on non-spatial memory examined in the ORT was the opposite. In addition, we showed that the effect of MA administration in adulthood on NMDA receptors is influenced by prenatal MA exposure, which seems to correlate with the spatial memory examined in the OLT.

scholarly journals Assessing the Effects of Redox Modifier MnTnBuOE-2-PyP 5+ on Cognition and Hippocampal Physiology Following Doxorubicin, Cyclophosphamide, and Paclitaxel Treatment

2020 ◽  
Vol 21 (5) ◽  
pp. 1867 ◽  
Author(s):  
Taylor McElroy ◽  
Taurean Brown ◽  
Fred Kiffer ◽  
Jing Wang ◽  
Stephanie D. Byrum ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Spatial Memory ◽  
Morris Water Maze ◽  
Water Maze ◽  
High Energy ◽  
Antioxidant Defenses ◽  
Memory Retention ◽  
Chemotherapy Treatment ◽  
Dendrite Morphology ◽  
Dendritic Length

Background: Chemotherapy treatment for breast cancer can induce cognitive impairments often involving oxidative stress. The brain, as a whole, is susceptible to oxidative stress due to its high-energy requirements, limited anaerobic respiration capacities, and limited antioxidant defenses. The goal of the current study was to determine if the manganese porphyrin superoxide dismutase mimetic MnTnBuOE-2-PyP (MnBuOE) could ameliorate the effects of doxorubicin, cyclophosphamide, and paclitaxel (AC-T) on mature dendrite morphology and cognitive function. Methods: Four-month-old female C57BL/6 mice received intraperitoneal injections of chemotherapy followed by subcutaneous injections of MnBuOE. Four weeks following chemotherapy treatment, mice were tested for hippocampus-dependent cognitive performance in the Morris water maze. After testing, brains were collected for Golgi staining and molecular analyses. Results: MnBuOE treatment preserved spatial memory during the Morris water-maze. MnBuOE/AC-T showed spatial memory retention during all probe trials. AC-T treatment significantly impaired spatial memory retention in the first and third probe trial (no platform). AC-T treatment decreased dendritic length in the Cornu Ammonis 1 (CA1) and dentate gyrus (DG) areas of the hippocampus while AC-T/MnBuOE maintained dendritic length. Comparative proteomic analysis revealed affected protein networks associated with cell morphology and behavior functions in both the AC-T and AC-T/MnBuOE treatment groups.

Sign in / Sign up

Export Citation Format

Share Document