1. Methods Objectives Results Conclusions References
Interferon βeta Ameliorates Amyloidosis And Increases Neurogenesis In The Hippocampus Of Lentivirus–Induced Rat model Of Alzheimer’s Disease
Sara Chavoshinezhad1, 2, Leila Dargahi3, Abolhassan Ahmadiani2, Homa Mohseni-Kouchesfehani1
1Department of Animal Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran
2Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3NeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Objectives
Alzheimer’s disease (AD) is a progressive neurodegenerative disease and the most common type of dementia. The impairment of learning and memory and neuronal loss are characteristics of AD, which are associated with the overproduction of beta amyloid (Aβ) peptide in the cortex and hippocampus. In addition, studies suggest that dysfunctional neurogenesis in the hippocampus might also contribute to the neurodegenerative process and memory deficits observed in AD. It is also known that neuro-inflammation can lead to Aβ aggregates formation which limit the survival of newborn neurons in the dentate gyrus(DG). Therefore, stimulating neural stem cells (NSCs) to replace lost neurons is a promising approach for AD treatment. Interferon beta (IFNβ) is the primary treatment used to combat inflammation and flare-ups in multiple sclerosis. IFNβ was reported to have anti-inflammatory and anti-apoptotic properties. The current study aimed to examine whether intranasal (IN) IFNβ treatment with high CNS bioavailability and minimal systemic side effects, could ameliorate memory impairment by decreasing amyloidosis and promoting neurogenesis in a rat model of AD.
A thflavin S staining method is also used to identify Aβ plaque deposition levels. Therapeutic effects of IN IFNβ delivery (1μg/kg, started from day 23 after injection and continued every other day for 14 total doses) were also investigated in AD animals.
Results
Our results showed that injection of LV-hAPPSw/Ind induced a significant decrease in the spontaneous alternation behavior compared with sham group, and this was accompanied by an increased number of APP positive cells and Aβ plaque deposition in the hippocampus of AD animals. IFNβ treatment attenuated cognitive deficit induced by LV-hAPPSw/Ind. In addition, IFNβ significantly decreased the number of APP positive cells and Aβ plaque deposition in the hippocampus of AD animals. Interestingly, Rats treated with IFNβ showed significantly increased numbers of Ki67 and DCX positive cells in the DG area of hippocampus.
The effect of intranasal (IN) insulin treatment on Aβ plaque level and protein expression of neurogenesis markers in the hippocampus. Thioflavin T staining (A) and Ki67 (B) and DCX (C)
Conclusions
The results of this study indicate that IFNβ treatment of AD-rats can enhance NSCs proliferation and neuronal differentiation by reduction of APP expression and Aβ plaque deposition which may finally lead to improvement of spatial cognitive function. Taken together, these results provide evidence that IFNβ can potentially be used as a therapeutic agent in treatment of AD. ##
Methods **
Lentiviruses (LV) encoding human amyloid protein precursor (hAPP) bearing Swedish and Indiana mutations (LV-hAPPSw/Ind) (3μl; 109 TU/ml/side) were injected bilaterally in the hippocampus CA1 area of adult male rats. Cognitive function was assessed using Y-maze task on day 43 after injection. Furthermore, we evaluated amyloid precursor protein (APP), Ki-67 (a proliferating cell marker) and doublecortin (DCX; an immature progenitor cell marker) immunolabelling in the hippocampus.
FIGURE 1 The effect of intranasal (IN) insulin treatment on working memory impairment induced by LV-APP injection. **P < 0.01 versus control group, ##P < 0.01 versus LV-APP group.
References