Folic acid ameliorates depression-like behaviour in a rat model of chronic unpredictable mild stress

Abstract

Background: Depression is characterized by significant and low mood. Classical antidepressants are still not adequate in treating depression because of undesirable side effects. Folic acid, a member of the vitamin B complex, in considered to be strongly associated with the function and development of the central nervous system. Thus, in this study, we established a model of depression through chronic unpredictable mild stress (CUMS) in rats and assessed the antidepressant effects and mechanisms of folic acid. Methods: Sprague-Dawley rats were randomly divided into four groups: control, chronic unpredictable mild stress (CUMS), CUMS treated with folic acid, and CUMS treated with citalopram. Rats were assessed in terms of weight change, open-field test and sucrose preference. Homocysteine, monoamine neurotransmitters, interleukin-6, brainderived neurotrophic factor (BDNF), β-endorphin levels in the serum and brains of rats were analysed. Results: Folic acid exhibited antidepressant-like effects in open-field and sucrose preference tests. Folic acid treatment effectively increased the levels of monoamine neurotransmitters, BDNF and β-endorphin, interleukin-6 and homocysteine levels were also significantly suppressed by folic acid administration. Conclusions: These findings serve as preclinical evidence that folic acid plays an antidepressant-like role in several pathways involving monoamine neurotransmitters. Thus, folic acid may be used as a potential antidepressant.

Neuroprotective Efficiency of Prodigiosins Conjugated with Selenium Nanoparticles in Rats Exposed to Chronic Unpredictable Mild Stress is Mediated Through Antioxidative, Anti-Inflammatory, Anti-Apoptotic, and Neuromodulatory Activities

“…Although the specific pathophysiological mechanisms underlying depression are not yet completely clear, animal and human studies have illustrated that dysfunctional intracerebral neurotransmission, such as 5-HT, NE, and DA, is positively associated with the development of depression. 80 In the current study, CUMS exposure disrupted cholinergic and monoaminergic transmission, as demonstrated by reduced hippocampal levels of AChE, 5-HT, DA and NE, which was associated with increased MAO activity. A previous report showed that the hyperactivity of the HPA axis is correlated with a reduction in 5-HT and NE levels in brain tissue.…”

“…Earlier studies have reported increased levels of pro-inflammatory cytokines in the prefrontal cortex of animal models of depression. 4 , 59 , 80 The inflammatory response that follows CUMS exposure has been suggested to be associated with enhanced COX-2/PGE2-driven inflammatory pathways and the increased activation of NF-κB, leading to increased pro-inflammatory cytokines production. 81 , 82 By contrast, the administration of Se nanoformulations exhibited neuroprotective activity via the suppression of the inflammatory cascade in epileptic mice and diabetic rats.…”

DL-3-n-butylphthalide Increases Collateriogenesis and Functional Recovery after Focal Ischemic Stroke in Mice

“…Instead, this study provides the important data for later time points (such as Day 14) to support restoration of LCBF and sustainable positive outcomes. NBP was long recognized as a neuroprotective drug in acute and chronic conditions [ 48 , 49 ]. The mechanistic reason for focusing on the possible association of NBP and collateral circulation was based on the roles of NBP in robust regulation of several vascular regenerative factors [ 50 ].…”

Neurotrophins as Key Regulators of Cell Metabolism: Implications for Cholesterol Homeostasis

“…Coherently with its hypoglycemic effect, NGF efficiently ameliorates the molecular alterations reminiscent of insulin resistance in basal forebrain cholinergic neurons [ 89 ]. In addition, NGF administration counteracts ER stress and apoptosis observed in Schwann cells during diabetic peripheral neuropathy, and efficiently attenuates neuronal death under glucose fluctuation in diabetic encephalopathy [ 90 , 91 ]. In contrast to BDNF and NGF, very little experimental evidence highlights the involvement of NT-3 or NT-4 in the regulation of energy homeostasis.…”