The extended psychological stress that occurs due to social isolation disrupts the hypothalamic–pituitary–adrenal (HPA) axis, which is considered the primary stress adaption pathway in the body. Indeed, GABAergic system components, including GABA enzyme, transports, and receptors, are expressed in the immune cells. GABA involves in inflammation regulation by modulating the production of proinflammatory cytokines through activating inflammatory signaling pathways such as nuclear factor-κB (NFκB) and mitogen-activated protein kinase (MAPK). Several studies had highlighted the regulatory role of GABA in neuroimmune functions. To date, the role of neuroinflammation in anxiety pathogenesis is not well established. 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. Thus, the activity of DHM on GABA ARs provides one possible mechanism for its role in anxiolysis. In addition, we found that DHM antagonizes the acute and chronic effects of alcohol on GABA ARs. We have demonstrated that dihydromyricetin (DHM), a major bioactive flavonoid extracted from Ampelopsis grossedentata, is a positive allosteric modulator (PAM) of GABAergic transmission, and thus has the potential to regulate anxiety-like behavior via its action on GABAergic receptors. Therefore, modifying GABA A receptor (GABA ARs) activity is a target for regulating anxiety. 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.Ĭlinical evidence indicates that GABAergic neurotransmission alteration involves in pathophysiology of anxiety disorders in humans. The pandemic is bringing up similar fears and mental distress, due to loss of family member(s) and loved ones. The pandemic also has led to an increase in posttraumatic stress disorder (PTSD). The rise in individuals suffering anxiety has been particularly noticeable during the ongoing COVID-19 pandemic that has resulted in quarantine and social isolation. Considering the ineffective therapeutics in the clinic due to treatment resistance, inconsistent patient adherence, and other exogenous factors, the prevalence of chronic anxiety continues to be on the rise. and are estimated to consume one-third of the country’s mental health spending. The results suggest that social isolation contributes to neuroinflammation, while DHM has the ability to improve neuroinflammation induced by anxiety.Īnxiety disorders are the largest class of mental health diseases in the U.S. Notably, DHM treatment counteracted these changes. Moreover, social isolation induced an increase in serum corticosterone level and activation in NF-κB pathway. 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. Socially isolated mice showed increased anxiety levels, reduced exploratory behaviors, and reduced gephyrin levels. Gephyrin protein expression, microglial profile changes, NF-κB pathway activation, cytokine level, and serum corticosterone were measured. The anxiety-like behaviors after DHM treatment were examined using elevated plus-maze and open field behavioral tests. MethodsĮight-week-old male C57BL/6 mice were housed under absolute social isolation for 4 weeks. 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. 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. 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. Although anxiolytic therapies are available, many patients still exhibit treatment resistance, relapse, or substantial side effects. and are estimated to consume one-third of the country’s mental health treatment cost. Anxiety disorders are the most prevalent mental illnesses in the U.S.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |