Abstract
BackgroundAnxiety disorders are the most prevalent mental illnesses in the U.S. and are estimated to consume one-third of the country’s mental health treatment cost. Although anxiolytic therapies are available, many patients still exhibit treatment resistance, relapse, or substantial side effects. Further, due to the COVID-19 pandemic and stay-at-home order, social isolation, fear of the pandemic, and unprecedented times, the incidence of anxiety has dramatically increased. Previously, we have demonstrated dihydromyricetin (DHM), the major bioactive flavonoid extracted from Ampelopsis grossedentata, exhibits anxiolytic properties in a mouse model of social isolation-induced anxiety. Because GABAergic transmission modulates the immune system in addition to the inhibitory signal transmission, we investigated the effects of short-term social isolation on the neuroimmune system.MethodsEight-week-old male C57BL/6 mice were housed under absolute social isolation for 4 weeks. The anxiety-like behaviors after DHM treatment were examined using elevated plus-maze and open field behavioral tests. Gephyrin protein expression, microglial profile changes, NF-κB pathway activation, cytokine level, and serum corticosterone were measured.ResultsSocially isolated mice showed increased anxiety levels, reduced exploratory behaviors, and reduced gephyrin levels. Also, a dynamic alteration in hippocampal microglia were detected illustrated as a decline in microglia number and overactivation as determined by significant morphological changes including decreases in lacunarity, perimeter, and cell size and increase in cell density. Moreover, social isolation induced an increase in serum corticosterone level and activation in NF-κB pathway. Notably, DHM treatment counteracted these changes.ConclusionThe results suggest that social isolation contributes to neuroinflammation, while DHM has the ability to improve neuroinflammation induced by anxiety.
Highlights
Anxiety disorders are the most prevalent mental illnesses in the U.S and are estimated to consume one-third of the country’s mental health treatment cost
We have demonstrated that dihydromyricetin (DHM) [(2R,3R)-3,5,7-trihydroxy-2(3,4,5-trihydroxyphenyl)-2,3-dihydrochromen-4-one], a major bioactive flavonoid extracted from Ampelopsis grossedentata, is a positive allosteric modulator (PAM) of GABAergic transmission, and has the potential to regulate anxiety-like behavior via its action on GABAergic receptors [9, 10]
Because GABAergic transmission modulates the immune system in addition to the inhibitory signal transmission, we investigate the effects of social isolation on the neuroimmune system
Summary
Anxiety disorders are the most prevalent mental illnesses in the U.S and are estimated to consume one-third of the country’s mental health treatment cost. Anxiolytic therapies are available, many patients still exhibit treatment resistance, relapse, or substantial side effects. Due to the COVID-19 pandemic and stay-athome order, social isolation, fear of the pandemic, and unprecedented times, the incidence of anxiety has dramatically increased. The rise in individuals suffering anxiety has been noticeable during the ongoing COVID-19 pandemic that has resulted in quarantine and social isolation [4]. The ongoing increase in cases of individuals suffering from anxiety disorders, coupled with the lack of effective medications for many, highlight the need for new treatment strategies to prevent or manage anxiety disorders
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