Research from the Salk Institute has unveiled that the astrocyte-secreted protein CCN1 plays a crucial role in stabilizing neural circuits in the adult brain. This discovery, detailed in a study published in Nature, highlights potential therapeutic avenues for treating neurological conditions such as Alzheimer’s disease, depression, and post-traumatic stress disorder (PTSD).
Traditionally, astrocytes have been viewed as mere support cells in the brain. However, this new study indicates that they actively contribute to maintaining the plasticity of neural circuits. “This study establishes the crucial role of astrocytes in actively stabilizing the connectivity of neuronal circuits,” stated Nicola Allen, PhD, who is the corresponding author and co-director of the Neuroimmunology Initiative at Salk. The research team focused on the mouse visual cortex to explore how astrocytes influence plasticity as animals age.
Neural circuits exhibit higher plasticity during youth, which allows for refinement and adaptation. As individuals mature, these circuits become more stable and less plastic. The research indicates that while stability is essential for maintaining functional connectivity, it may inhibit the brain’s ability to adapt. Allen’s team found that the expression of CCN1 is pivotal in regulating this balance. They observed that increasing CCN1 levels enhanced the maturation of inhibitory neurons and oligodendrocytes, which ultimately reduced neuroplasticity.
To investigate the role of CCN1 further, the researchers employed advanced techniques, including transcriptomic analysis and in vivo imaging. The findings revealed that removing CCN1 from astrocytes destabilized the circuits responsible for binocular vision and diminished myelination, underscoring the protein’s integral role in maintaining circuit stability.
Manipulating CCN1 levels may provide a pathway to re-establish plasticity in the adult brain, potentially aiding recovery from injuries or trauma. The protein is known to interact with a variety of extracellular components across different cell types, including excitatory and inhibitory neurons, oligodendrocytes, and microglia. By binding to integrin proteins on cell surfaces, CCN1 can coordinate the maturation of these cells, thereby influencing plasticity.
First author Laura Sancho, PhD, a postdoctoral researcher in Allen’s lab, emphasized the importance of stable circuits for proper brain function. “Maintaining stable circuits is important for proper brain function, but the consequence is that neural plasticity and remodeling are repressed in the adult brain,” she noted. Sancho and Allen’s findings pave the way for new therapeutic strategies targeting CCN1, potentially transforming approaches to brain injury and conditions that involve neuroplasticity deficits.
The implications of this research extend beyond basic neuroscience. With neurological diseases affecting millions globally, the identification of CCN1 as a critical regulator of neuroplasticity could lead to innovative treatments. Further studies will be necessary to explore the therapeutic potential of CCN1 and its role in adult brain health.
