Journal of Rafsanjan University of Medical Sciences

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Background and Objective: Cholinergic neurons of nucleus basalis magnocellularis (NBM) have a key role in learning and memory process. It has been shown that these neurons are degenerated in patients with Alzheimer disease (AD). On the other hand, using the cholinomimetic agents and acetylcholinesterase inhibitors improve cognition in these patients. Some studies have shown that the frontal cortex receives some cholinergic projections from NBM. In the present study, the effect of intrafrontal cortex administration of physostigmine ( acetylcholinesterase inhibitor) was investigated on active avoidance learning on the animal model of AD.
Materials and Methods: In this experimental study, NBM was lesioned electricaly in Wistar male rats, (250-300g body weight) for making the animal model of AD. Because the frontal cortex receives cholinergic projections from NBM, different doses of physostigmine (2.5, 5, 7.5 µg/µl) were injected bilaterally into the frontal cortex of lesioned rats 20 minutes before active avoidance learning (8 sessions, 30 steps in each session) in Y-maze.
Results: The results showned that active avoidance learning was decreased significantly in NBM-lesioned group. Also intrafrontal cortex injection of phsostigmine (2.5, 5, and 7.5 µg/µl) significantly severed NBM lesion-induced learning deficiency.
Conclusion: The findings of this study suggest that the cholinergic projection of NBM to frontal cortex in lesioned animals has a negative role on this type of learning. It seems that other neurotransmitter systems such as glutamate and other afferent projections from different brain areas to frontal cortex probably are involved in this phenomenon.
Key words: NBM, Physostigmine, Frontal Cortex, Alzheimer Disease, Rat

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Background and Objectives: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized clinically by progressive memory loss and subsequent dementia. The aim of this study was to evaluate the synergist effect of folic acid and vitamin B₁₂ on spatial memory in adult male rat Alzheimer's disease.
Material and methods: In this experimental study, 49 male Wistar rats were randomly divided into 7 groups: (7 rats in each group): control(intact), NBM lesion group, which received electrically- induced lesion (0.5 m A, 3s) in NBM, sham group ( the electrode was impaled in to the NBM with no lesion), NBM lesion + folic acid 5mg/kg, NBM lesion+ vitamin B₁₂ 5mg/kg, NBM lesion+ folic acid- vitamin B₁₂, NBM lesion + saline. Acquisition and retention testing was done by using an eight-radial arm maze, in which the patterns of arm entries were recorded in each group for calculating working memory errors, reference memory error ,and latency. Data were analyzed using one-way ANOVA and Tukey's post hoc test.
Results: The results showed that there was a significant difference between the control and lesion groups in the parameters of the reference memory error, working memory error ,and elapsed time (P˂0.05). The administration of folic acid and vitamin B₁₂alone did not have any significant effect on spatial memory parameters compared with the lesion group. Co-administration folic acid- vitamin B₁₂ resulted in a reduction in the reference and working memory errors and the time spent in the eight-arm radial laser maze.
Conclusion: According to the results, the NMB lesion resulted in a reduction in spatial memory and co-administration of folic acid and vitamin B₁₂ resulted in improved spatial memory.
Key words: Alzheimer disease, Nucleus Basalis Magnocellularis, Folic acid, Vitamin B₁₂, Radial maze
 
Funding: This research was funded by Shahid Chamran University.
Conflict of interest: None declared.
Ethical approval: The Ethical Committee of Shahid Chamran University approved the study.
 
How to cite this article: Eskandary A, Moazedi A.A, Mamani N. The Synergist Effects of Folic Acid and Vitamin B₁₂ on Spatial Memory in Adult Male Rat Model of Alzheimer's Disease. J Rafsanjan Univ Med Sci 2018; 16(10): 925-38. [Farsi]