Effect of Atorvastatin on Memory in Albino Mice

Rr, Biswas; S, Rao A S R; Kadali,

doi:10.7860/jcdr/2014/9730.5089

Cited by 2 publications

(4 citation statements)

References 20 publications

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“…We did not find any effect of atorvastatin on blood glucose levels in this model suggesting its action on the learning deficit is related to other mechanisms, which may include antioxidant effects. As noted for other studies [ 29 ], no precise correlation between cholesterol and behavior can be made here as body weight is taken as a surrogate of cholesterol levels. However, the lipid profile is technically difficult to measure because of the small size of the mice and difficulty in collecting adequate blood for measurements.…”

Section: Discussionmentioning

confidence: 99%

“…or liraglutide (200 μg/kg, i.p.) was administered daily for 28 d. Atorvastatin and liraglutide doses were selected based on previous reports [ 29 , 30 , 31 , 32 , 33 ]. Liraglutide was used as a positive control for its effect in reducing alloxan-induced hyperglycemia.…”

Section: Methodsmentioning

confidence: 99%

“…Liraglutide was used as a positive control for its effect in reducing alloxan-induced hyperglycemia. The 10 mg/kg atorvastatin treatment dose selected in these studies was the lowest neuroprotective dose suggested by the reports [ 29 , 30 , 31 , 32 , 33 ]. All behavioral tests were observed by two investigators blinded to the treatments.…”

Section: Methodsmentioning

confidence: 99%

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Atorvastatin reduces alloxan-induced impairment of aversive stimulus memory in mice

Kukula

Günaydın

2022

Asian Biomedicine

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Background An association between dysregulated glucose levels in patients with diabetes mellitus and detrimental effects on the central nervous system, particularly in Alzheimer disease, has been recognized. Atorvastatin treatment has improved memory and cognition in some patients with diabetes mellitus and Alzheimer disease. Objectives To determine possible neuroprotective effects of atorvastatin on memory and cognition by measuring changes in an adverse stimulus avoidance learning deficit induced by alloxan in a murine model of diabetes mellitus and impaired memory and cognition. Methods We administered 150 mg/kg and 100 mg/kg alloxan in saline (intraperitoneally, i.p.) at a 48 h interval to produce a model of diabetes mellitus in male BALB/c mice. An oral glucose tolerance test (OGTT) was used to assess blood glucose regulation. After demonstrating hyperglycemia in mice (n = 7 per group) we administered vehicle (saline, i.p.), atorvastatin (10 mg/kg, i.p.), or liraglutide (200 μg/kg, i.p.) for 28 d except for those in a negative control group, which were given saline instead of alloxan, and a group administered atorvastatin alone, which were given saline instead of alloxan followed by atorvastatin (10 mg/kg, i.p.) for 28 d. Locomotor activity was measured 24 h after the final drug treatments, and subsequently their learned behavioral response to an adverse electrical stimulus to their plantar paw surface in a dark compartment was measured using a passive avoidance apparatus (Ugo Basile) in a model of impaired memory and cognition associated with Alzheimer disease. To determine any deficit in their learned avoidance of the adverse stimulus, we measured the initial latency or time mice spent in an illuminated white compartment before entering the dark compartment in the learning trial, and on the day after learning to avoid the adverse stimulus, the retention period latency in the light compartment and time spent in the dark compartment. Results Atorvastatin alone produced no significant change in blood glucose levels (F 4,10 = 0.80, P = 0.55) within 2 h. Liraglutide decreased blood glucose levels after 0.5 h (F 4,10 = 11.7, P < 0.001). We found no significant change in locomotor activity in any group. In mice with alloxan-induced diabetes, atorvastatin significantly attenuated the decreased avoidance associated with the diabetes (F 4,30 = 38.0, P = 0.02) and liraglutide also significantly attenuated the decreased avoidance (F 4,30 = 38.0, P < 0.001). Atorvastatin alone had no significant effect on the adversive learned response compared with vehicle treatment (F 4,30 = 38.0, P > 0.05). Atorvastatin significantly decreased the time mice with alloxan-induced diabetes spent in the dark compartment compared with mice in the diabetes group without atorvastatin treatment (F 4,30 = 53.9, P = 0.046). Liraglutide also significantly reduced the time mice with alloxan-induced diabetes spent in the dark compartment compared with vehicle-treated mice with alloxan-induced diabetes (F 4,30 = 53.9, P < 0.001). Atorvastatin treatment alone had no significant effect on the time mice spent in dark compartment compared with the control group (F 4,30 = 53.9, P > 0.05). Conclusion Atorvastatin significantly attenuated the adverse stimulus avoidance learning deficit in the alloxan-induced murine model of diabetes suggesting decreased impairment of memory and cognition.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Atorvastatin reduces alloxan-induced impairment of aversive stimulus memory in mice

Kukula

Günaydın

2022

Asian Biomedicine

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“…In addition to the cholesterol-lowering action, the success of statins became increasingly connected with broader pleiotropic effects [29][30][31][32]. Statins are increasingly being associated with potential protective effects on pathologies beyond cardiovascular diseases (e.g., respiratory [33][34][35][36][37], carcinogenic [38][39][40][41][42][43], viral [44][45][46][47][48], neurodegenerative [49][50][51][52][53]). The exact off-target mechanisms of statins, along with the reason why many patients show resistance to this class of drugs, are still unknown.…”

Section: Introductionmentioning

confidence: 99%

[18F]Atorvastatin: synthesis of a potential molecular imaging tool for the assessment of statin-related mechanisms of action

et al. 2020

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Background: Statins are lipid-lowering agents that inhibit cholesterol synthesis and are clinically used in the primary and secondary prevention of cardiovascular diseases. However, a considerable group of patients does not respond to statin treatment, and the reason for this is still not completely understood. [ 18 F]Atorvastatin, the 18 Flabeled version of one of the most widely prescribed statins, may be a useful tool for statin-related research. Results: [ 18 F]Atorvastatin was synthesized via an optimized ruthenium-mediated late-stage 18 F-deoxyfluorination. The defluoro-hydroxy precursor was produced via Paal-Knorr pyrrole synthesis and was followed by coordination of the phenol to a ruthenium complex, affording the labeling precursor in approximately 10% overall yield. Optimization and automation of the labeling procedure reliably yielded an injectable solution of [ 18 F]atorvastatin in 19% ± 6% (d.c.) with a molar activity of 65 ± 32 GBq·μmol −1 . Incubation of [ 18 F]atorvastatin in human serum did not lead to decomposition. Furthermore, we have shown the ability of [ 18 F]atorvastatin to cross the hepatic cell membrane to the cytosolic and microsomal fractions where HMG-CoA reductase is known to be highly expressed. Blocking assays using rat liver sections confirmed the specific binding to HMG-CoA reductase. Autoradiography on rat aorta stimulated to develop atherosclerotic plaques revealed that [ 18 F]atorvastatin significantly accumulates in this tissue when compared to the healthy model. Conclusions: The improved ruthenium-mediated 18 F-deoxyfluorination procedure overcomes previous hurdles such as the addition of salt additives, the drying steps, or the use of different solvent mixtures at different phases of the process, which increases its practical use, and may allow faster translation to clinical settings. Based on tissue uptake evaluations, [ 18 F]atorvastatin showed the potential to be used as a tool for the understanding of the mechanism of action of statins. Further knowledge of the in vivo biodistribution of [ 18 F]atorvastatin may help to better understand the origin of off-target effects and potentially allow to distinguish between statin-resistant and non-resistant patients.

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Effect of Atorvastatin on Memory in Albino Mice

Cited by 2 publications

References 20 publications

Atorvastatin reduces alloxan-induced impairment of aversive stimulus memory in mice

Atorvastatin reduces alloxan-induced impairment of aversive stimulus memory in mice

[18F]Atorvastatin: synthesis of a potential molecular imaging tool for the assessment of statin-related mechanisms of action

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