Hevin is a circulating signal molecule that appears to be involved in the regulation of connectivity between neurons in the brain, inducing the formation of synapses. To the degree that this increases neuroplasticity, one would expect it to help resist the harmful effects of Alzheimer's disease pathology. It does this not by reducing the ongoing damage to neurons and their connections, but by allowing the brain to better adapt to or recover from that damage. This sort of approach is a losing game in the long term, as pathology will grow to outpace attempts to compensate, but it is better than nothing.
Dementia, characterized by loss of cognitive abilities in the elderly, poses a significant global health challenge. This study explores the role of astrocytes, one of most representative glial cells in the brain, in mitigating cognitive decline. Specifically, we investigated the impact of Hevin (also known as SPARC-like1/SPARCL-1), a secreted glycoprotein, on cognitive decline in both normal and pathological brain aging. Hevin has been reported to induce the development of structurally formed but functionally silent synapses. Importantly, Hevin has been pointed out as a candidate factor that reverts age-associated cognitive decline following administration of blood from young to aged animals.
By using adeno-associated viruses, we overexpressed Hevin in hippocampal astrocytes of middle-aged APP/PSEN mice, an established Alzheimer's disease (AD) model. Results demonstrated that Hevin overexpression attenuates cognitive decline, as evidenced by cognitive tests, increased pre- and postsynaptic markers colocalization, and altered expression of synaptic mediators, as revealed by proteomic profiling. Importantly, Hevin overexpression did not influence the deposition of amyloid-β plaques in the hippocampus, a hallmark of AD pathology. Furthermore, the study extended its findings to middle-aged wild-type animals, revealing improved cognitive performance following astrocytic Hevin overexpression.
Link: https://doi.org/10.1111/acel.14493
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