Impaired Memory and Evidence of Histopathology in CA1 Pyramidal Neurons through Injection of Aβ1-42 Peptides into the Frontal Cortices of Rat.
BACKGROUND
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-β peptides (Aβ) 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 Aβ injection. Furthermore, Nissl staining showed that Aβ neurotoxicity caused shrinkage of the CA1 pyramidal neurons. Neurodegeneration was clearly evident from Fluoro-jade labeled neurons in Aβ treated rats. Moreover, higher NF-κB immunoreactive CA1 pyramidal neurons were remarkably observed in Aβ treated rats. Ultrastructural analysis using electron microscopy also showed the evidence of subcellular abnormalities. Melatonin treatment in this model of AD prevented Aβ-induced increased NF-κB from immunoreaction and neurodegeneration.


CONCLUSIONS
This study suggests that injection of Aβ 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 Aβ.
Department of Neuroscience, School of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.; Shefa Neuroscience Research Center, Khatam Al-anbia Hospital, Tehran, Iran.
Mohammad Javad
MJ
Eslamizade
Department of Pathology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Zahra
Z
Madjd
Department of Anatomical Sciences, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Homa
H
Rasoolijazi
Department of Neuroscience, School of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.; Shefa Neuroscience Research Center, Khatam Al-anbia Hospital, Tehran, Iran.
Fatemeh
F
Saffarzadeh
Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.
Vahid
V
Pirhajati
Shefa Neuroscience Research Center, Khatam Al-anbia Hospital, Tehran, Iran.
Hadi
H
Aligholi
Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Mahyar
M
Janahmadi
Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.
Mehdi
M
Mehdizadeh
Amyloid-β; Animal model; Frontal cortex; Hippocampus; Melatonin; Memory