impaired memory and evidence of histopathology in ca1 pyramidal neurons through injection of aβ1-42 peptides into the frontal cortices of rat

Introduction: Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders, which has much benefited from animal models to find the basics of its pathophysiology. In our previous work (Haghani, Shabani, Javan, Motamedi, & Janahmadi, 2012), a non-transgenic rat model of AD was used in electrophysiological studies. However, we did not investigate the histological aspects in the mentioned study. Methods: An AD model was developed through bilateral injection of amyloid-&beta peptides (A&beta) into the frontal cortices. Behavioral and histological methods were used to assess alterations in the memory and (ultra)structures. Furthermore, melatonin has been administered to assess its efficacy on this AD model. Results: Passive avoidance showed a progressive decline in the memory following A&beta injection. Furthermore, Nissl staining showed that A&beta neurotoxicity caused shrinkage of the CA1 pyramidal neurons. Neurodegeneration was clearly evident from Fluoro-jade labeled neurons in A&beta treated rats. Moreover, higher NF-&kappaB immunoreactive CA1 pyramidal neurons were remarkably observed in A&beta treated rats. Ultrastructural analysis using electron microscopy also showed the evidence of subcellular abnormalities. Melatonin treatment in this model of AD prevented A&beta- induced increased NF-&kappaB from immunoreaction and neurodegeneration. Discussion: This study suggests that injection of A&beta into the frontal cortices results in the memory decline and histochemical disturbances in CA1 pyramidal neurons. Furthermore, melatonin can prevent several histological changes induced by A&beta.