A recent investigation has unveiled a significant link between sulfate groups attached to complex sugar molecules known as ‘glycosaminoglycans’ (GAGs) and brain plasticity, which plays a pivotal role in learning, memory retention, and recuperation. This groundbreaking study, disclosed on Wednesday, highlights the profound influence of GAGs on cognitive functions.
The study, published in the American Chemical Society journal, delves into the intricacies of sugars, revealing that the sugars responsible for sweetening fruits, candies, or cakes are merely a subset of the diverse range of sugars. These sugars, when intricately combined, form a multitude of complex sugar structures.
Glycosaminoglycans (GAGs) are formed by coupling other chemical entities, including sulfate groups. Linda Hsieh-Wilson, the lead investigator of the project, explains that by examining the chemistry of GAGs within the brain, researchers can glean insights into brain plasticity. The hope is that this knowledge can be harnessed in the future to restore or enhance neural connections related to memory.
These sugars exert regulatory control over numerous proteins, and their configurations undergo changes during both developmental processes and disease states, adding a layer of complexity to their role, Hsieh-Wilson further elaborates.
Furthermore, the study sheds light on chondroitin sulfate, the most prevalent form of GAG found in the brain. This compound is pervasive within the extracellular matrix enveloping the brain’s myriad cells. Notably, chondroitin sulfate is responsible for the formation of “perineuronal nets,” which enwrap individual neurons, stabilizing their synaptic connections.
Remarkably, when researchers genetically manipulated mice by eliminating the ‘Chst11’ gene, responsible for creating key sulfation patterns on chondroitin sulfate, they observed disruptions in the perineuronal nets. Intriguingly, the absence of sulfation motifs led to an increase in the number of nets, subsequently altering the types of synaptic connections between neurons.
Equally compelling, the affected mice demonstrated an inability to recognize previously encountered peers, suggesting a direct impact on social memory. Notably, these perineuronal nets may exhibit greater dynamism than previously assumed, functioning during both childhood and adulthood. When ‘Chst11’ was specifically targeted in the brains of adult mice, the same effects on perineuronal nets and social memory were evident. Hsieh-Wilson underscores that this outcome implies the potential to manipulate these nets during adolescence or adulthood, potentially rewiring or reinforcing specific synaptic connections.