Effect of neuregulin on expressions of apoptosis and nuclear factor kappa B in hippocampus of Alzheimer's disease model rats

Abstract

Objective To investigate the effect of neuregulin1β(NRG1β)on the learning memory abilities and the neuronal apoptosis and the expressions of nuclear factor kappa B (NFκB) in experimental Alzheimer's disease model in rats induced with beta-amyloid protein1-40 (Aβ1-40) injection. To explore the mechanisms of NRG in improving the capabilities of learning and memory. Methods Thirty adult healthy male wistar rats were randomly divided into control group (n=10), model group (n=10) and treated group (n=10). Alzheimer's disease models were established by stereotactically injecting Aβ1-40 into the left lateral ventricle, and treated by injecting NRG1β(0.3μg·kg-1) into the right lateral ventricle. The learning and memory abilities of rats were evaluated with Y-electric maze before the experiment and 7 days after making Alzheimer's disease models and 14 days after treatment. HE staining was used to observe the structure of hippocampal neurons. The neuronal apoptosis of hippocampus was investigated by TUNEL assay. The expressions of NFκB in hippocampal neurons were determined with immunohistochemistry technique. Results Compared with control group(57.50±1.58, 7.20±1.03), the model group rats(59.50±2.79, 7.50±1.08)showed low cognitive ability(t=20.36, 5.28, P<0.05), the hippocampal pyramidal cells of rats in the model group were sparse and disturbed pyramidal cells , noticeable neuron loss. The number of neuronal apoptosis and the expressions of NFκB increased significantly than those in control group (P<0.05). Compared with model group (79.10±4.12, 4.40±0.69), NRG1β strikingly improved cognitive ability(67.70±4.90, 5.80±0.63)and normal cell structure(t=5.63, 4.69, P<0.05). The expressions of NFκB(25.90±6.67)reduced while the number of neuronal apoptosis(23.50±3.89) decreased markablely than those(41.10±7.95, 29.30±7.24)in model group(t=4.63, 2.23, P<0.05). Conclusion NRG1β might decrease the neuronal apoptosis by inhibiting NFκB expressions, so that to improve the learning and memory abilities of experimental dementia rats. Key words: Neuregulins; Alzheimer's disease; Beta-amyloid protein; Apoptosis; Nuclear factor kappa B