Effect of ladostigil treatment of aging rats on gene expression in four brain areas associated with regulation of memory: Selective changes by ladostigil in gene expression in aging brain

Episodic and spatial memory decline in aging and are controlled by the hippocampus, perirhinal, frontal and parietal cortices and the connections between them. Ladostigil, a drug with antioxidant and anti-inflammatory activity, was shown to prevent the loss of episodic and spatial memory in aging rats. To better understand the molecular effects of aging and ladostigil on these brain regions we characterized the changes in gene expression using RNA-sequencing technology in rats aged 6 and 22 months. We found that the changes induced by aging and chronic ladostigil treatment were brain region specific. In the hippocampus, frontal and perirhinal cortex, ladostigil decreased the overexpression of genes regulating calcium homeostasis, ion channels and those adversely affecting synaptic function. In the parietal cortex, ladostigil increased the expression of several genes that provide neurotrophic support, while reducing that of pro-apoptotic genes and those encoding pro-inflammatory cytokines and their receptors. Ladostigil also decreased the expression of axonal growth inhibitors and those impairing mitochondrial function. Together, these actions could explain the protection by ladostigil against age-related memory decline.