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 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.

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.

scholarly journals Protective Effects of Aminoguanidine against Sodium Metavanadate-Induced Spatial Memory Retention Impairment in Morris Water Maze

2019 ◽  
Vol 25 (2) ◽  
pp. 93-99
Author(s):  
Kaveh Tabrizian ◽  
Morteza Esmaeilei ◽  
Mahmoud Hashemzaei ◽  
Arezoo Esmaeilzaei ◽  
Sahar Fanoudi ◽  
...  
Keyword(s):  
Spatial Memory ◽  
Morris Water Maze ◽  
Water Maze ◽  
Protective Role ◽  
Memory Retention ◽  
Protective Effects ◽  
Nitric Oxide Synthase Inhibitor ◽  
Sodium Metavanadate ◽  
Pre Treatment ◽  
Synthase Inhibitor

Background: Vanadium is a potential neurotoxic agent widely distributed in the environment. Understanding the neurotoxic mechanisms of vanadium on learning and memory seems necessary. Methods: We investigated the time-dependent (1-week, 2- week and 4-week) effects of sodium metavanadate (SMV) (25 mg/kg/day; pre-training oral administration) and 4-day intraperitoneal injections of aminoguanidine (AG) as a selective inducible nitric oxide synthase inhibitor (10, 50, and 100 mg/kg) on spatial memory retention in Morris water maze. Animals were trained for 4 days and tested 48 h after the last training trial. Results: The data showed that 4-week oral pre-treatment with SMV (25 mg/kg/day) induced spatial memory retention deficits and decreased the time spent in the target quadrant. We found that 4-day administration of different doses of AG during training trials significantly decreased the time and distance of finding the hidden platforms. Additionally, SMV-induced spatial memory retention impairments were prevented in animals received combined SMV (25 mg/kg/day, 4 weeks) and AG (10 mg/kg/day, 4 days). Conclusion: Our findings showed the protective role of AG on SMV-induced spatial memory retention deficits.

Intrahippocampal co-administration of nicotine and O-acetyl-L-carnitine prevents the H-89-induced spatial learning deficits in Morris water maze

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Mahmoud Hashemzaei ◽  
Najmeh Baratzadeh ◽  
Iraj Sharamian ◽  
Sahar Fanoudi ◽  
Mehdi Sanati ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Spatial Memory ◽  
Morris Water Maze ◽  
Spatial Learning ◽  
Water Maze ◽  
Synergistic Effects ◽  
Deionized Water ◽  
Learning Deficits ◽  
Learning Impairments ◽  
Morris Water Maze Task

Abstract Objectives H-89 (a protein kinase AII [PKA II] inhibitor) impairs the spatial memory in the Morris water maze task in rats. In the present study, we aimed to study the protective effects of nicotine and O-acetyl-L-carnitine against H-89-induced spatial memory deficits. Methods Spatial memory impairment was induced by the bilateral intrahippocampal administration of 10 µM H-89 (dissolved in dimethyl sulfoxide, DMSO) to rats. The rats then received bilateral administrations of either nicotine (1 μg/μL, dissolved in saline) or O-acetyl-L-carnitine (100 μM/side, dissolved in deionized water) alone and in combination. Control groups received either saline, deionized water, or DMSO. Results The H-89-treated animals showed significant increases in the time and distance travelled to find hidden platforms, and there was also a significant decrease in the time spent in the target quadrant compared to DMSO-treated animals. Nicotine and O-acetyl-L-carnitine had no significant effects on H-89-induced spatial learning impairments alone, but the bilateral intrahippocampal co-administration of nicotine and O-acetyl-L-carnitine prevented H-89-induced spatial learning deficits and increased the time spent in the target quadrant in comparison with H-89-treated animals. Conclusions Our results indicated the potential synergistic effects of nicotine and O-acetyl-L-carnitine in preventing protein kinase AII inhibitor (H-89)-induced spatial learning impairments.

scholarly journals Long-term potentiation is independent of the C-tail of the GluA1 AMPA receptor subunit

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Javier Díaz-Alonso ◽  
Wade Morishita ◽  
Salvatore Incontro ◽  
Jeffrey Simms ◽  
Julia Holtzman ◽  
...  
Keyword(s):  
Spatial Memory ◽  
Morris Water Maze ◽  
Ampa Receptor ◽  
Water Maze ◽  
Long Term Potentiation ◽  
Receptor Subunit ◽  
Terminal Domain ◽  
Term Potentiation ◽  
Ampa Receptor Subunit

We tested the proposal that the C-terminal domain (CTD) of the AMPAR subunit GluA1 is required for LTP. We found that a knock-in mouse lacking the CTD of GluA1 expresses normal LTP and spatial memory, assayed by the Morris water maze. Our results support a model in which LTP generates synaptic slots, which capture passively diffusing AMPARs.

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