الفهرس 
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Abstract
Summary
Depression is a severe mental condition; 350 million people are victims of it globally, according to WHO. It ranks as the fourth most common cause of disability worldwide. Genetic, epigenetic, environmental, and other variables contribute to depression.
An angiogenic mitogen is VEGF. It has historically been linked to vasculogenesis and angiogenesis. It also appears essential in the pathophysiology of MDD and plays a crucial role in neurogenesis and neuroprotection.
A significant function for MAPK, particularly the ERK subtype, in the pathophysiology of depression, is supported by mounting data.
Classical anti-depressant drugs that focus on restoration of brain monoamines are recommended for treatment of depressed patients, though patients suffered from several undesirable side effects as headache, drowsiness, nervousness, insomnia, etc. So, it is urgent to develop other therapeutics with minimal side effects.
It is well known that exercise positively impacts bodily processes and depression symptoms. Several pathways include neuroplasticity, neuroanti-inflammatory, cognitive, psychosocial, and anti-inflammatory.
Vitamin D has recently acquired popularity due to its anti-inflammatory, neuromodulatory, and antioxidant characteristics, essential to its antidepressant benefits.
The purpose of the current study was to examine the impact of exercise and/or vitamin D on rats that had undergone experimentally induced depression in order to determine their potential mechanisms of action through examination of the VEGF-mediated MAPK/ERK pathway.
Fifty male adult Wistar rats were divided as follows:
1) group 1: healthy control.
2) group 2: depression (pathological control).
3) group 3: depression + vitamin D.
4) group 4: depression + exercise.
5) group 5: depression + vitamin D + exercise.
They were subjected to euthanasia, and brain was examined for:
a) Gene expression of VEGF and ERK by qRT-PCR.
b) Estimation of MDA and GSH by colorimetry.
c) Estimation of TNF-α, BDNF, DA and NE by ELISA.
Results revealed that:
1. All treated groups showed a significant reduction in MDA, TNF-, VEGF, and ERK compared to group 2.
2. Significantly higher levels of GSH, BDNF, DA, and NE in all treated groups compared to group 2.
3. There was no discernible difference between groups 3 and 4.
4. MDA, TNF-α, VEGF, and ERK levels in group 5 were significantly lower than those in the other treatment groups, according to 4.
5. GSH, BDNF, DA, and NE levels in group 5 were significantly higher than those in the other treated groups.
In conclusion, vitamin D and/or physical activity may be helpful to therapies for depression. The activation of the VEGF-mediated MAPK/ERK pathway, which may affect the neurotransmitters, oxidative stress, and inflammatory state, may cause this.