RESUMEN
l-methionine (L-met) is a substantial non-polar amino acid for normal development. L-met is converted to homocysteine that leads to hyperhomocysteinemia and subsequent excessive homocysteine in serum resulting in stimulating oxidative stress and vascular dementia. Several studies have found that hyperhomocysteine causes neuronal cell damage, which leads to memory impairment. Caffeic acid is a substrate in phenolic compound discovered in plant biosynthesis. Caffeic acid contains biological antioxidant and neuroprotective properties. The neuroprotective reaction of caffeic acid can protect against the brain disruption from hydrogen peroxide produced by oxidative stress. It also enhances GSH and superoxide dismutase activities, which protect against neuron cell loss caused by oxidative stress in the hippocampus. Hence, we investigated the protective role of caffeic acid in hippocampal neurogenesis and cognitive impairment induced by L-met in rats. Six groups of Sprague Dawley rats were assigned including control, L-met (1.7 g/kg/day), caffeic acid (20, 40 mg/kg), and L-met + caffeic acid (20, 40 mg/kg) groups. Spatial and recognition memories were subsequently examined using novel object location (NOL) and novel object recognition (NOR) tests. Moreover, the immunofluorescence technique was performed to detect Ki-67/RECA-1, bromodeoxyuridine (BrdU)/NeuN and p21 markers to represent hippocampal neurogenesis changes. The results revealed decreases in vasculature related cell proliferation and neuronal cell survival. By contrast, cell cycle arrest was increased in the L-met group. These results showed the association of the spatial and recognition memory impairments. However, the deterioration can be restored by co-administration with caffeic acid.
RESUMEN
Hippocampal neurogenesis occurs throughout life, but it declines with age. D-galactose (D-gal) enhances cellular senescence through oxidative stress leading to neurodegeneration and memory impairment. Caffeic acid (CA) acts as an antioxidant via decreasing brain oxidative stress. This study aims to investigate the advantages of CA in alleviating the loss of memory and neurogenesis production in the hippocampus in aged rats activated by D-gal. Fifty-four male Sprague-Dawley rats were unpredictably arranged into six groups. In the D-gal group, rats were administered D-gal (50 mg/kg) by intraperitoneal (i.p.) injection. For the CA groups, rats received 20 or 40 mg/kg CA by oral gavage. In the co-treated groups, rats received D-gal (50 mg/kg) and CA (20 or 40 mg/kg) for eight weeks. The results of novel object location (NOL) and novel object recognition (NOR) tests showed memory deficits. Moreover, a decline of neurogenesis in the hippocampus was detected in rats that received D-gal by detecting rat endothelial cell antigen-1 (RECA-1)/Ki-67, 5-bromo-2'-deoxyuridine (BrdU)/neuronal nuclear protein (NeuN), doublecortin (DCX) by means of staining to evaluate blood vessel associated proliferating cells, neuronal cell survival and premature neurons, respectively. By contrast, CA attenuated these effects. Our results postulate that CA attenuated the impairment of memory in D-gal-stimulated aging by up-regulating levels of hippocampal neurogenesis.