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

Neuroprotective effects of carnosic acid in an experimental model of Alzheimer's disease in rats

Alzheimer's disease is the most common type of neurodegenerative disorder. It has been suggested that oxidative stress can be one of the pathological mechanisms of this disease. Carnosic acid [CA] is an effective antioxidant substance and recent studies have shown that its electrophilic compounds play a role in reversing oxidative stress. Thus we tried to find out whether CA administration protects hippocampal neurons, preventing neurodegeneration in rats, Animals were divided into four groups: Sham-operated [sham], CA-pretreated sham-operated [sham+CA], untreated lesion [lesion] and CA-pretreated lesion [lesion+CA]. Animals in all groups received vehicle or vehicle plus CA [CA: 10mg/ kg] intra-peritoneally one hour before surgery, again the same solution injected 3-4 hours after surgery [CA: 3 mg/kg] and repeated each afternoon for 12 days. A lesion was made by bilateral intra-hippocampal injection of 4 microl of beta amyloid protein [1.5 nmol/microl] or vehicle in each side. 14 days after surgery, the brains were extracted for histochemical studies. Data was expressed as mean +/- SEM and analyzed using SPSS statistical software. Results showed that pretreatment with carnosic acid can reduce cellular death in the cornu ammonis 1 [CA1] region of the hippocampus in the lesion+CA group, as compared with the lesion group. Carnosic acid may be useful in protecting against beta amyloid-induced neurodegeneration in the hippocampus

beneficial effect of [-]-epigallocatechin-3-gallate in an experimental model of Alzheimer's disease in rat: a behavioral analysis

Progressive cognitive decline is one of the hallmark symptoms of Alzheimer's disease [AD] which can be modeled by beta-amyloid injection into specific regions of brain. Since epigallocatechin-3-gallate [EGCG] is a potent antioxidant agent which its role against oxidative stress and inflammation has been shown in prior studies, we tried to determine whether EGCG administration protects against beta-amyloid-induced memory and coordination impairment in rats. Animals [male Wistar rats] were divided into four groups: sham operated, EGCG-pretreated sham operated [sham + EGCG], untreated lesion [lesion], and EGCG-pretreated lesion [lesion + EGCG]. Animals in lesion, lesion + EGCG, and sham + EGCG groups received sterile saline or saline plus EGCG [10 mg/kg] intraperitoneally one day pre-surgery and every other day for three weeks. The lesion was induced one day after EGCG pretreatment by injection of 4 microl of sterile saline or water containing 2 nmol/microl beta-amyloid [1-40] into the hippocampal fissure. For behavioral analysis, psychomotor coordination [PMC] index and spontaneous alternation behavior were assessed using Rota-rod Treadmill and Y-maze, respectively at the third week post-lesion. We found that beta-amyloid [1-40] injection into hippocampus can decrease these behavioral indexes in lesion group in comparison with sham group which is similar to behavioral changes in AD. On the other hand, pretreatment with EGCG can improve the PMC index and spatial Y-maze alternation in the lesion + EGCG group in comparison with lesion group. We concluded that EGCG can be effective in restoring beta-amyloid-induced behavioral derangements in rats regarding coordination and memory abilities