Anti-Stress and Anti-Depressive Effects of Spinach Extracts on a Chronic Stress-Induced Depression Mouse Model through Lowering Blood Corticosterone and Increasing Brain Glutamate and Glutamine Levels

Abstract

Spinach is one of the most widely consumed vegetables, and is known as for both physical and mental health maintenance. However, there is little information about how spinach protects one from stress. In the present study, we created three extracts from Spinach oleracea L., (frozen powder (FP), water extract (WE), and ethanol extract (EE)), and examined their anti-stress and anti-depressive effects on mouse using a chronic immobilization stress (CIS) regimen. FP, WE, and EE showed different free amino acid constituents. Calorie-balanced diets derived from each extract were tested for their ability to reduce blood corticosterone (CORT) levels in naïve mice. Diets supplemented with FP or EE induced lower blood CORT levels than a normal diet, but the WE diet did not. Mobility duration and sucrose preference were increased by FP and EE supplementation in the CIS-induced depression animal models. Moreover, FP and EE increased glutamate and glutamine levels in the medial prefrontal cortex (mPFC) compared with CIS-induced depressed group. These results suggest that spinach has anti-stress and anti-depressive properties by lowering CORT and increasing glutamate and glutamine levels in the mPFC.

Glutamine Supplementation Prevents Chronic Stress-Induced Mild Cognitive Impairment

“…CIS markedly increased plasma CORT levels in the STR group, but this increase was inhibited by Gln supplementation ( Figure 1D). These results are similar to those reported in our previous studies [4,15,16,18], confirming that CIS induces a stress response, and supplementation with Gln blunts its effects.…”

“…High levels of glucocorticoids, caused by repeated stress, can alter receptor-possessing cells and trigger oxidative stress responses in different brain regions, including the hippocampus and the PFC [24][25][26]. As shown in our previous studies [4,15,16], a Gln-supplemented diet reversed elevated blood CORT levels back to baseline. This was the impetus for investigating Gln supplementation in stress-induced MCI, and Figure 1 shows that Gln also reversed elevated blood CORT levels back to CTL levels.…”

“…We used chronic immobilization to induce cognitive impairment in young male mice ( Figure 1A), the same process used for chronic stress-induced depression in our previous studies [4,15,16,18]. As expected, CIS reduced body weight in the stressed groups ( Figure 1B), without a difference in food intake ( Figure 1C).…”

“…Our previous studies show that Gln is a key mediator of astrocyte-neuron interactions for glutamatergic signaling, and that the direct infusion of Gln into mice increased both Glu and Gln levels in the prefrontal cortex (PFC) as well as enhanced glutamatergic activity [4,6]. Furthermore, we showed that dietary Gln supplementation prevented chronic stress-induced decreases in Glu and Gln levels, their transporter protein levels, and overall glutamatergic signaling in mouse PFC [4,15,16]. Gln has also been reported to be neuroprotective against oxidative stress and inflammation [17].…”

“…We induced MCI in mice using a CIS regimen, a model used for chronic stress-induced depression in our previous studies [4,15,16,18]. It is well known that chronic stress is a main cause of cognitive impairment and early onset of dementia [3,21,22].…”