Betaine attenuates oxidative stress and cognitive dysfunction in an amyloid β-induced rat model of Alzheimer's disease

Abstract

Background and purpose: Increasing evidence indicates that oxidative stress is an important factor in the pathogenesis and progression of Alzheimer's disease (AD). Betaine is trimethylglycine with antioxidant and neuroprotective properties. The present study aimed to evaluate the possible beneficial effects of betaine on oxidative stress and memory deficits induced by intrahippocampal injection of amyloid beta (Aß) in an AD model.

Experimental approach: Forty adult male Wistar rats were divided into 5 equal groups: the control and Aß groups which received oral gavage of saline (1 mL daily) for 14 days. The other 3 groups (betaine + Aß) received betaine (5, 10, and 15 mg/kg, orally) for 14 consecutive days. On the 15^th day, all of the groups were injected bilaterallyintrahippocampal of Aß (5 µg/µL), except controls that were injected with normal saline as a vehicle. Seven days after the Aß injection, memory was assessed in a passive avoidance test. Changes in catalase activities and glutathione peroxidase, glutathione, and malondialdehyde concentrations were investigated to determine the antioxidant activity in the rat hippocampus.

Findings/results: Data showed that betaine pretreatment of Aß-injected rats improved memory in avoidance tasks. In addition, betaine pretreatment attenuated oxidative stress.

Conclusion and implications: The current findings showed that oral administration of betaine could prevent Aß-induced impairment of memory possibly through suppression of oxidative stress in the hippocampus area of rats.

Keywords: Alzheimer's disease; Amyloid beta; Betaine; Learning and memory; Oxidative stress.

Fig. 1

The experimental protocols for the betaine effect on oxidative stress and cognitive dysfunction in an amyloid β-induced rat model of Alzheimer’s disease.

Fig. 2

The coronal sections of the rat brain show the approximate location of the CA1 injection sites in the experiments.

Fig. 3

Passive avoidance apparatus.

Fig. 4

Effect of betaine on memory deficit induced by Aß injection in inhibitory avoidance task. Betaine at 5, 10, and 15 mg/kg significantly increased step-through latency in Aß-injected rats. Data are presenting the mean ± SEM, n = 8. ***P< 0.001 indicates significant differences in comparison with the control group; ^##P < 0.01 versus Aß group. Aß, Amyloid beta.

Fig. 5

Effect of betaine at 5, 10, and 15 mg/kg on GSH concentration in the hippocampus of Aß-injected rats. Data are expressed as mean ± SEM, n = 8. **P< 0.01 indicates significant differences in comparison with the control group; ^##P < 0.01 versus Aß group. Aß, Amyloid beta; GSH, glutathione.

Fig. 6

Effect of betaine at 5, 10, and 15 mg/kg on GPx activity in the hippocampus of Aß-injected rats. Data represent mean ± SEM, n = 8. ***P< 0.001 indicates significant differences in comparison with the control group; ^##P < 0.01 and ^##P < 0.001 versus Aß group. Aß, Amyloid beta; GPx, glutathione peroxidase.

Fig. 7

Effect of betaine at 5, 10, and 15 mg/kg on MDA concentrations in the hippocampus of Aß-injected rats. Data are expressed as mean ± SEM, n = 8. ***P< 0.001 indicates significant differences in comparison with the control group; ^##P < 0.01 versus Aß group. Aß, Amyloid beta; MDA, malondialdehyde.

Fig. 8

Effect of betaine at 5, 10, and 15 mg/kg on CAT activity in the hippocampus of Aß-injected rats. Data are presented as mean ± SEM, n = 8. *P< 0.05 indicates significant differences in comparison with the control group; ^#P < 0.05 and ^##P < 0.01 versus Aß group. Aß, Amyloid beta; CAT, catalase.