Apoptosis induced by β amyloid protein in rat brain and protection by melatonin in the rat brains

Objective To investigate both the role of apoptosis in the pathogenesis of Aβ and the therapeutic effect of melatonin on the neurotoxicity of Aβ in the rat brains. Methods Aβ 1-40 was microinjected into CA1 subfield in the right hippocampus of rats.Seven days later, apoptosis of the neurons was determined with the use of Nissl staining, hematoxylin eosin staining,TUNEL staining and transmission electron microscopy(TEM).The expression of Bax/Bcl 2 was determined with immunohistochemistry SABC method. Results In the Aβ group, hematoxylin eosin staining showed many neurons in the CA1 subfied cell bodies became shrunken,whereas the chromatin were condensed and deeply stained. TUNEL staining indicated that lots of cells with nuclei brown yellow stained and ringed. The TEM examination revealed compact patches or rings or cells like crescent moons with condensed nuclear chromatin but with no apparent nuclear membrane disruption. In comparision with the control groups,the expression of the Bax in the hippocampal CA1 subfields in the Aβ group was stronger,but the expression of Bcl 2 showed no obvious difference among the above three groups. The numbers of the neurons in the hippocampal CA1 subfields in the melatoin group were 47.4±5.9,more than in the Aβ group (29.4± 4.5), but less than in the normal saline control group (79.8±7.6)or in the sham operation control group (83.1±8.5). Apoptotic cells in the melatonin group (8.4±3.7)were less than in the Aβ group (18.9±6.1). Conclusions The result of this study indicated that Aβ could induce the neuronal apoptosis in the rat brains, and the stronger expression of Bax might play an important role in those neuronal apoptosis, whereas, melatonin could markedly inhibit the neurotoxicity of Aβ in the rat brains, which suggested that complementing of melatonin might be beneficial for the prevention and therapy of Alzheimer′s Disease.