Fig. 6.

Schematic summary of the various pathways involved in social isolation-induced neuroinflammation and anxiety-like behaviors. Social isolation (SI) induces stress that triggers disruption in the hypothalamus–pituitary–adrenal axis (HPA), increase in the levels of corticosterone (CORT), and overactivity in the sympathetic nervous system (SNS), which in turn might trigger NF-κB pathway activation and enhance the level of proinflammatory cytokines. Social isolation induces a reduction in pre-, post-, and/or extra-synaptic GABA_ARs, and in gephyrin expression leading to impairment in GABAergic neurotransmission. GABA_ARs are also expressed in microglia and astrocytes. Proinflammatory cytokines and GABA_AR disruption provokes microglia and astrocytes activation leading to further neuroinflammation damages and anxiety-like behaviors. DHM is a positive modulator of GABA_AR that plays a role in counteracting neuroinflammation and contribute to the anxiolytics effect