SUMMARY & CONCLUSION
The present study was carried out in order to investigate the prophylactic effect of vitamin D3, folic acid and memantine against scopolamine induced alzeheimer disease and therapeutic effect of vitamin D3 , folic acid and fluoxetine against corticosterone induced depression-like behavior in rats. It was carried into 2 parts, each part carried on 6 groups of adult male Sprague-Dawley rats.
In the first part, 36 male albino rats were classified into 6 equal groups (6 rats in each group). Group I was control group receive given 0.9% saline only. Group II was injected scopolamine (2.5 mg/kg) intraperitoneal once daily for 21 days. Group III was given folic acid (4 mg/kg, i.p) administrated once daily for 21 days with scopolamine. Group IV was given vitamin D3 (42 IU/kg) was administrated subcutaneously once daily for 21 days with scopolamine. Group V was given vitamin D3 (42 IU/kg sc) and folic acid (4 mg/kg, i.p) once daily with scoplolamine for 21 days. Group VI was given memantine (20 mg/kg i.p) was administrated once daily with scopolamine for 21 days. All these groups were subjected for assessment of cognitive performance through morris water maze test. Biochemical tests include {hippocampal tissue levels of brain derived neurotrophic factor (BDNF), amyloid beta 1-42 level (Aβ1-42), glutathione reductase (GR) and acetyl choline} and histopathological changes in the brain.
In the second part, 36 male albino rats were classified into 6 equal groups (6 rats in each group). Group I was control group was given 0.9% saline only. Group II was corticosterone intraperitoneal in a dose of 40mg/kg for 3weeks (21 days). Group III was given folic acid at a dose of (50mg/kg, p.o.) once daily immediately after corticosterone injection for 3weeks (21 days). Group IV was given vitamin D3 (12mg/kg p.o.) once daily immediately after corticosterone injection for 3weeks (21 days). Group V was given vitamin D3 (12mg/kg p.o.) and folic acid (50mg/ kg p.o.) once daily immediately after corticosterone injection for 3weeks (21 days). Group VI was given fluoxetine (20mg/kg p.o.) once daily immediately after corticosterone injection for 3weeks (21 days). All these groups were subjected for assessment of behavior changes through open field test and tail suspension test. Biochemical tests through measurement of Brain neurotransmitters levels (serotonin and dopamine), brain tissue level of brain derived neurotrophic factor (BDNF) and tumor necrosis factor (TNF-α) and histopathological changes of brain tissue.
The obtained results of this study could be summarized as follow:-
In the first part of the study:
Data obtained in the present study pointed out that the experimentally induced alzeheimer untreated rats showed significant decrease in brain tissue levels of BDNF, acetyl choline (Ach), glutathione reductase and significant increase in amyloid peptide 1-42 (Aβ1-42) level in brain tissue. Also lead to a significant memory impairment in Morris water maze test, as evident by the significant increase of initial acquisition latency (IAL), as well as, the first and second retention latencies (1st and 2nd RL) to reach the platform. Also changes in histopathological finding in the brain as compared with the control group were seen.
Treatment of experimentally induced alzeheimer rats with folic acid or vitamin D3 or memantine separately or combined group (folic acid + vitamin D3) resulted in significant improvement of biochemical parameters in the form of significant incease of brain tissue levels of BDNF, acetyl choline (Ach), glutathione reductase with significant reduction of amyloid peptide 1-42 level. Also lead to a significant memory improvement in Morris water maze test, as evident by the significant decrease of initial acquisition latency (IAL), as well as, the first and second retention latencies (1st and 2nd RL) to reach the platform. Also showed improvement of histopathological changes occurred in the brain. But combined group and memantine-treated group resulted in more significant improvement of these parameters as compared with other treated groups and control group.
In the second part of this study:
Data obtained in the present study pointed out that the experimentally induced untreated depression-like behavior group significant decrease in brain tissue level of BDNF, brain neurotransmitter (serotonin and dopamine) with significantly increase of TNF-α, alteration of behavior in the form of increase immobility time of tail suspension test (TST) and increase latency time, decrease number of central square crossing, rearing and line crossing through open field test.
Treatment of experimentally induced alzeheimer rats with folic acid or vitamin D3 or memantine separately or combined group (folic acid + vitamin D3) resulted in significant improvement of biochemical parameters in the form of significant increase in brain tissue level of BDNF, serotonin and dopamine with significantly decrease in TNF-α, alteration of behavior in the form of decrease immobility time of tail suspension test (TST) and decrease latency time, increase number of central square crossing, rearing and line crossing through open field test. But combined treated group and fluoxetine-treated group showed more significant improvement of biochemical tests as compared to other treated groups and control group.
From previous data one may assume that (conclusions):
• Vitamin D3 and folic acid could have neuroprotective effect in AD and depression that involves many mechanisms; including increase of hippocampal neurotrophic factors as BDNF, rise of the antioxidant defense system (glutathione reductase), reduction of the burden of Aβ-peptide, inhibit production of pro-inflammatory cytokines (TNF-α) and increase the synthesis neurotransmitters, including serotonin and dopamine through increase the expression of genes encoding for tyrosine hydroxylase leading to improvement of the brain functions.
• Folic acid alone could not prevent progression of alzeheimer disease or depression, so we can use it as adjuvant therapy for standard treatment or combined with vitamin D3.
• Vitamin D3 alone or combined with folic acid could improve pathological changes in the brain in alzeheimer disease and depression.
• Vitamin D3 could considered as promising agents for the development of new prophylactic and therapeutic neuroprotectors.
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