CY6463 (FORMERLY IW-6463)

A Central Nervous System-penetrant Soluble Guanylate Cyclase Stimulator Reduced Spine Density Loss in Aged Rats and Mice

Society for Neuroscience Annual Meeting (2018)

Susana S. Correia, Juli E. Jones, Christopher Rex, Guang Liu, Andrew Carvalho, Peter Germano, Rajesh R. Iyengar, Christopher J. Winrow, Mark G. Currie, and John R. Hadcock

This research describes the effects of IW-6463, a central nervous system-penetrant sGC stimulator, on neuronal spine density in aged rats.

Aged mice treated with IW-6463 for 4 months had neuronal spine density greater than that observed in aged control mice and similar to that observed in young control mice

Dendritic spines protrude from the dendritic shafts of neurons and are involved in the synaptic processes that underlie cognitive function. Loss of neuronal spines is associated with neurogenerative disorders, is correlated with decreased synaptic function, and may contribute to cognitive dysfunction. We evaluated the effects of IW-6463 on the density of spines of pyramidal neurons in the hippocampus of aged mice. As shown, after 4 months of treatment, the density of hippocampal neuronal spines in IW-6463-treated aged mice was not only greater than that of vehicle-treated aged mice controls but was at the same level as that of the young control. Restoration of spine density has the potential to provide neuroprotective effects and improve synaptic function in neurodegenerative diseases. Correia et al. (SfN 2018) poster presentation

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