circ_0000831 and miR-16-5p in Depression | Neuroinflammatory Regulation via Non-Coding RNA

Recent findings published in [International Journal of Biological Macromolecules (2024)](已发2024-Int J Biol Macromoly.pdf) reveal that circ_0000831 , a circular non-coding RNA, plays a significant role in suppressing neuroinflammatory responses. This discovery has implications for understanding the molecular basis of Major Depressive Disorder (MDD) and may lead to new diagnostic tools and therapeutic strategies.

In this article, we will explore:

• The functional role of circ_0000831
• Its interaction with miR-16-5p
• How this axis affects neuroinflammation in depression
• Potential applications in RT-PCR detection kits
• Integration with other circRNA studies in psychiatry

circ_0000831 is a covalently closed, non-coding RNA formed by back-splicing of the ZNF609 gene . Unlike linear mRNAs, circRNAs are resistant to exonuclease degradation, making them ideal candidates for stable biomarkers in bodily fluids such as blood, saliva, and cerebrospinal fluid.

In the 2024 study, circ_0000831 was found to be significantly downregulated in LPS-treated BV2 microglial cells , suggesting its involvement in inflammatory regulation within the central nervous system (CNS).

One of the primary functions of many circRNAs is to act as microRNA (miRNA) sponges , sequestering miRNAs and preventing them from binding to their target mRNAs. This regulatory mechanism allows circRNAs to indirectly influence gene expression at the post-transcriptional level.

The study shows that circ_0000831 directly binds to miR-16-5p , reducing its availability to regulate downstream targets involved in inflammation.

miR-16-5p has been implicated in promoting neuroinflammatory signaling by targeting anti-inflammatory genes and enhancing cytokine production. When circ_0000831 is overexpressed, it effectively reduces miR-16-5p activity, leading to decreased levels of pro-inflammatory cytokines such as:

• TNF-α
• IL-6
• IL-1β

These findings suggest that circ_0000831 serves as an endogenous anti-inflammatory agent in microglial cells.

Neuroinflammation is increasingly recognized as a key contributor to the pathophysiology of Major Depressive Disorder . Inflammatory mediators released by activated glial cells can impair synaptic plasticity, disrupt neurotransmitter balance, and contribute to depressive behaviors.

By modulating the circ_0000831/miR-16-5p axis , it may be possible to:

• Reduce glial activation
• Lower inflammatory cytokine release
• Improve behavioral outcomes in depression models

This makes the axis a promising therapeutic target and potential diagnostic biomarker for MDD.

Quantitative real-time PCR (qPCR) using divergent primers is the gold standard for detecting circRNAs like circ_0000831. These primers specifically amplify the back-spliced junction , distinguishing circRNAs from their linear counterparts.

To detect miR-16-5p, stem-loop RT primers followed by TaqMan-based qPCR are commonly used due to their high specificity and sensitivity.

Researchers used lentiviral vectors to either overexpress or knock down circ_0000831 in BV2 microglial cells and primary mouse microglia. Functional assays included:

• ELISA for cytokine measurement
• Western blotting for inflammatory pathway proteins
• Immunofluorescence staining for glial activation markers

These experiments confirmed that circ_0000831 overexpression inhibits LPS-induced inflammation , while its knockdown exacerbates the response.

The discovery of circ_0000831’s anti-inflammatory effects via miR-16-5p adds another layer to our understanding of how non-coding RNAs influence depression pathology . As part of a growing family of circRNAs associated with MDD, circ_0000831 provides both a biomarker candidate and a potential therapeutic target .

With tools like the MDD CircRNA RT-PCR Detection Kit , researchers can now investigate these interactions in greater depth, paving the way for personalized diagnostics and targeted interventions in mental health care.