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.

Improving effect of chronic resveratrol treatment on central monoamine synthesis and cognition in aged rats

“…These effects were also accompanied by a lower content of 5-HT, DA, and NA, and by reduced levels of metabolites (5-HIAA and HVA). The agerelated decline in monoaminergic function in hippocampus and striatum is believed to be partially responsible for memory disorders and for the prevalence of neurodegenerative diseases during senescence (Collier et al 2004;Cools et al 2011;Esteban et al 2010a, b;Haider et al 2014;Hussain and Mitra 2000;Luine et al 1990;Míguez et al 1999), which is in agreement with the agerelated impairment in working memory that is found in this work (assessed by an hippocampal-dependent test, the eight-arm radial maze test). The brain is the body tissue with the largest oxygen consumption, being extremely sensitive to oxidative damage.…”

“…Furthermore, the activity of antioxidant enzymes undergo a significant age-related decrease in brain (Keller et al 2005). Indeed, in both aged humans and rodents, age-related cognitive impairment and neurodegenerative changes have been correlated to oxidative damage accumulation in lipids, proteins, and nucleic acids, which could lead to the increased neurotransmitter systems' vulnerability to oxidative stress (Dias et al 2007;Haider et al 2014; see Butterfield et al 2006 for review). In this regard, it has been reported a reduced TPH and TH activities during normal aging brain that has been related to an inefficient phosphorylation and/or an oxidative damage of these enzymes (Cash et al 1998;De la Cruz et al 1996;Hussain and Mitra 2000).…”

Circulating IGF-1 deficiency exacerbates hypertension-induced microvascular rarefaction in the mouse hippocampus and retrosplenial cortex: implications for cerebromicrovascular and brain aging

“…Circulating IGF-1 levels and blood pressure measurements Although the factors responsible for the deleterious effects of aging on behavior and neuronal function (Baciu et al 2016;Berghuis et al 2015;Campbell et al 2014;Doi et al 2015;Haider et al 2014;Hofmann et al 2014;Kumar and Thakur 2015;Lopez et al 2014;Manich et al 2014;Salminen et al 2014;Samaras et al 2014;Sarubbo et al 2015;Loprinzi 2016;Wallis et al 2016) are not completely understood, there is strong evidence that in elderly humans a decline in circulating IGF-1 levels (Franco et al 2014) plays a critical pathophysiological role. To understand the effects of IGF-1 deficiency on the cerebral microcirculation in the present study, we used a novel mouse model of adult-onset isolated endocrine IGF-1 deficiency, which phenotypically better mimics age-related IGF-1 deficiency observed in humans that most other available rodent models of GH/IGF-1 deficiency (Arum et al 2014a;Hill et al 2015;Rojanathammanee et al 2014;Wiesenborn et al 2014;Arum et al 2014b;Schneider et al 2014).…”

A high dose of short term exogenous d-galactose administration in young male rats produces symptoms simulating the natural aging process

“…EPM is a behavioral task to assess memory function in rats [26]. The maze used consisted of four arms of equal dimensions; two open arms (50 × 10 cm) that crossed with two closed arms having walls of 40 cm high.…”