Impaired memory and evidence of histopathology in CA1 pyramidal neurons through Injection of Abeta1-42 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, and 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 [Abeta] 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 Abeta injection. Furthermore, Nissl staining showed that Abeta neurotoxicity caused shrinkage of the CA1 pyramidal neurons. Neurodegeneration was clearly evident from Fluoro-jade labeled neurons in Abeta treated rats. Moreover, higher NF-kappaB immunoreactive CA1 pyramidal neurons were remarkably observed in Abeta treated rats. Ultrastructural analysis using electron microscopy also showed the evidence of subcellular abnormalities. Melatonin treatment in this model of AD prevented Abeta- induced increased NF-kappaB from immunoreaction and neurodegeneration

Discussion: This study suggests that injection of Abeta 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 Abeta

Suppressive effects of resveratrol treatment on the intrinsic evoked excitability of CA1 pyramidal neurons

Objective: Resveratrol, a phytoalexin, has a wide range of desirable biological actions. Despite a growing body of evidence indicating that resveratrol induces changes in neu-ronal function, little effort, if any, has been made to investigate the cellular effect of resveratrol treatment on intrinsic neuronal properties

Materials and Methods: This experimental study was performed to examine the acute effects of resveratrol [100 NM] on the intrinsic evoked responses of rat Cornu Ammonis [CA1] pyramidal neurons in brain slices, using whole cell patch clamp recording under current clamp conditions

Results: Findings showed that resveratrol treatment caused dramatic changes in evoked responses of pyramidal neurons. Its treatment induced a significant [P<0.05] increase in the after hyperpolarization amplitude of the first evoked action potential. Resveratrol-treated cells displayed a significantly broader action potential [AP] when compared with either control or vehicle-treated groups. In addition, the mean instantaneous firing frequency between the first two action potentials was significantly lower in resveratrol-treated neurons. It also caused a significant reduction in the time to maximum decay of AP. The rheobase current and the utilization time were both significantly greater following resveratrol treatment. Neurons exhibited a significantly depolarized voltage threshold when exposed to resveratrol

Conclusion: Results provide direct electrophysiological evidence for the inhibitory effects of resveratrol on pyramidal neurons, at least in part, by reducing the evoked neural activity