Age-related learning and memory deficits in rats: role of altered brain neurotransmitters, acetylcholinesterase activity and changes in antioxidant defense system

Abstract

Oxidative stress from generation of increased reactive oxygen species or free radicals of oxygen has been reported to play an important role in the aging. To investigate the relationship between the oxidative stress and memory decline during aging, we have determined the level of lipid peroxidation, activities of antioxidant enzymes, and activity of acetylcholine esterase (AChE) in brain and plasma as well as biogenic amine levels in brain from Albino-Wistar rats at age of 4 and 24 months. The results showed that the level of lipid peroxidation in the brain and plasma was significantly higher in older than that in the young rats. The activities of antioxidant enzymes displayed an age-dependent decline in both brain and plasma. Glutathione peroxidase and catalase activities were found to be significantly decreased in brain and plasma of aged rats. Superoxide dismutase (SOD) was also significantly decreased in plasma of aged rats; however, a decreased tendency (non-significant) of SOD in brain was also observed. AChE activity in brain and plasma was significantly decreased in aged rats. Learning and memory of rats in the present study was assessed by Morris Water Maze (MWM) and Elevated plus Maze (EPM) test. Short-term memory and long-term memory was impaired significantly in older rats, which was evident by a significant increase in the latency time in MWM and increase in transfer latency in EPM. Moreover, a marked decrease in biogenic amines (NA, DA, and 5-HT) was also found in the brain of aged rats. In conclusion, our data suggest that increased oxidative stress, decline of antioxidant enzyme activities, altered AChE activity, and decreased biogenic amines level in the brain of aged rats may potentially be involved in diminished memory function.

Fig. 1

Effect of age on brain and plasma lipid peroxidation in young and aged rats. Data are means ± SD (n = 6) and expressed as micromoles of MDA per gram of brain (a) or MDA per milliliter of plasma (b). Data are analyzed for significant difference by Student’s t test; *p < 0.01 compared with young rats

Fig. 2

Effect of age on brain (a) and plasma (b) AChE activity in rats. Data are means ± SD (n = 6), and activity is expressed as micromoles per minute per gram in brain or micromoles per minute per milliliter in plasma. Data are analyzed for significant difference by Student’s t test; *p < 0.01 compared with young rats

Fig. 3

Effect of age on activities of brain antioxidant enzymes SOD (a), CAT (b), and GPx (c) in rats. Data are means ± SD (n = 6). SOD activity is expressed as units per gram of brain whereas CAT and GPx activities are expressed as micromoles per minute per gram. Data are analyzed for significant difference by Student’s t test; *p < 0.01 compared with young rats

Fig. 4

Effect of age on activities of plasma antioxidant enzymes SOD (a), CAT (b), and GPx (c) in rats. Data are means ± SD (n = 6). SOD activity is expressed as units per milliliter of plasma whereas CAT and GPx activities are expressed as micromoles per minute per milliliter. Data are analyzed for significant difference by Student’s t test; *p < 0.01 compared with young rats

Fig. 5

Effect of age on the memory of rats tested in MWM as STM (a) and LTM (b). Values are means ± SD (n = 6). Data are analyzed for significant difference by Student’s t test; *p < 0.01 compared with young rats

Fig. 6

Effect of age on the memory of rats tested in EPM as STM (a) and LTM (b). Values are means ± SD (n = 6). Data are analyzed for significant difference by Student’s t test *p < 0.01 versus young rats

Fig. 7

HPLC chromatogram of standard solution (a), biogenic amines in the whole brain of young and aged rats (b) and effect of age on concentration of brain monoamine levels in rats (c). Values are means ± SD (n = 6). Data are analyzed for significant difference by Student’s t test *p < 0.01 versus young rats