Inflammation and Connexin 43 profiles in the prefrontal cortex are relevant to stress susceptibility and resilience in mice.

Pharmacol Biochem Behav

State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China; School of Pharmacy, Hunan University of Traditional Chinese Medicine & Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, Changsha 410208, China. Electronic address:

Published: June 2024

AI Article Synopsis

  • - Depression is a common chronic mental illness that varies in response to stress among individuals, with some showing resilience while others display negative psychological effects, possibly linked to molecular mechanisms involving connexin 43 (Cx43) in the brain.
  • - Dysfunction of Cx43 in the prefrontal cortex (PFC) is associated with depressive behaviors, and stress exposure notably reduces Cx43 protein levels in susceptible mice but not in resilient ones, as observed in behavioral tests.
  • - The study indicates that inflammation is prevalent in central nervous system dysfunction and suggests that understanding the role of Cx43 and inflammatory signals may help develop therapeutic strategies to enhance resilience against stress-related disorders.

Article Abstract

Depression is a major chronic mental illness worldwide, characterized by anhedonia and pessimism. Exposed to the same stressful stimuli, some people behave normally, while others exhibit negative behaviors and psychology. The exact molecular mechanisms linking stress-induced depressive susceptibility and resilience remain unclear. Connexin 43 (Cx43) forms gap junction channels between the astrocytes, acting as a crucial role in the pathogenesis of depression. Cx43 dysfunction could lead to depressive behaviors, and depression down-regulates the expression of Cx43 in the prefrontal cortex (PFC). Besides, accumulating evidence indicates that inflammation is one of the most common pathological features of the central nervous system dysfunction. However, the roles of Cx43 and peripheral inflammation in stress-susceptible and stress-resilient individuals have rarely been investigated. Thus, animals were classified into the chronic unpredictable stress (CUS)-susceptible group and the CUS-resilient group based on the performance of behavioral tests following the CUS protocol in this study. The protein expression of Cx43 in the PFC, the Cx43 functional changes in the PFC, and the expression levels including interleukin (IL)-1β, tumor necrosis factor-α, IL-6, IL-2, IL-10, and IL-18 in the peripheral serum were detected. Here, we found that stress exposure triggered a significant reduction in Cx43 protein expression in the CUS-susceptible mice but not in the CUS-resilient mice accompanied by various Cx43 phosphorylation expression and the changes of inflammatory signals. Stress resilience is associated with Cx43 in the PFC and fluctuation in inflammatory signaling, showing that therapeutic targeting of these pathways might promote stress resilience.

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http://dx.doi.org/10.1016/j.pbb.2024.173757DOI Listing

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