Curcumin Ameliorates the Cd-Induced Anxiety-like Behavior in Mice by Regulating Oxidative Stress and Neuro-Inflammatory Proteins in the Prefrontal Cortex Region of the Brain

Abstract

Age-related neurodegenerative diseases and vascular dementia are major challenges to the modern health care system. Most neurodegenerative diseases are associated with impaired spatial working memory and anxiety-like behavior. Thus, it is important to understand the underlying cellular mechanisms of neurodegenerative diseases in different regions of the brain to develop an effective therapeutic approach. In our previous research paper, we have reported the ameliorative effect of curcumin in Cd-induced hippocampal neurodegeneration. However, recently many researchers had reported the important role of the prefrontal cortex in higher cognitive functions. Therefore, to look into the cellular mechanism of curcumin protection against Cd-induced prefrontal cortex neurotoxicity, we investigated spatial working memory, anxiety-like behavior and analyzed prefrontal cortex inflammatory markers (IL-6, IL-10, and TNFα), antioxidant enzymes (SOD, GSH, and CAT), and pro-oxidant MDA level. Further, we conducted histological studies of the prefrontal cortex in Swiss albino mice exposed to cadmium (2.5 mg/kg). We observed that curcumin treatment improved the spatial working memory and anxiety-like behavior of mice through reduction of prefrontal cortex neuroinflammation and oxidative stress as well as increasing the number of viable prefrontal cortex neuronal cells. Our result suggests that environmental heavy metal cadmium can induce behavioral impairment in mice through prefrontal cortex cellular inflammation and oxidative stress. We found that curcumin has a potential therapeutic property to mitigate these behavioral and biochemical impairments induced by cadmium.

Cadmium‐induced pyroptosis is mediated by PERK/TXNIP/NLRP3 signaling in SH‐SY5Y cells

“…For instance, increased exposure to Cd was shown that caused memory damage by affecting antioxidant enzymes in the brain tissue of newborn pups 67 . All the above studies indicate that reduced antioxidant capacity following cadmium exposure gives rise to serious structure damage and all kinds of dysfunction of the central nervous system 68–70 . As expected, we pretreated SH‐SY5Y cells with NAC, which is known as an antioxidant, 71,72 the result showed it was significantly alleviated Cd‐induced upregulation of p‐PERK protein.…”

“…(n = 3). (*p < .05; **p < .01; ***p < .001 compared with the control group; # p < .05; ## p < .01; ### p < .001 compared with the CdCl 2 group).structure damage and all kinds of dysfunction of the central nervous system [68][69][70]. As expected, we pretreated SH-SY5Y cells with NAC, which is known as an antioxidant,71,72 the result showed it was significantly alleviated Cd-induced upregulation of p-PERK protein.…”

Central injection of abscisic acid attenuates mood disorders induced by subchronic stress in male mice

“…Because oxidative damage and inflammation are involved in neuropsychiatric disorders (Gelders et al., 2018 ; McManus & Heneka, 2017 ; Yaribeygi et al., 2018 ), antioxidants may be able to reduce the symptoms of such disorders. For example, curcumin ameliorates spatial working memory and anxiety‐like behavior through reduction of prefrontal cortex neuroinflammation and oxidative stress (Namgyal et al., 2021 ). In addition, it has been reported that gallic acid improves anxiety and locomotor activity and memory deficits induced by chronic stress (Dhingra et al., 2014 ).…”

Possible Effects and Mechanisms of Dietary Natural Products and Nutrients on Depression and Anxiety: A Narrative Review

“…This also could be because antioxidants with low dose would show antioxidant activity in vivo, but they with high dose would exhibit pro-oxidative activity in vivo [ 132 , 133 , 134 ]. Additionally, in a cadmium-exposed mouse model, curcumin decreased anxiety-like behaviors by promoting the production of viable prefrontal cortex neuronal cells, and suppressing neuroinflammation in prefrontal cortex [ 135 ]. In addition, the intermediate dose of blackberry juice decreased anxiety-like behaviors, and the anxiolytic mechanism might be similar to diazepam [ 136 ].…”