Hippocampal SIRT1 improves cognitive impairment by deacetylating tau protein in diabetic models.

Diabetes mellitus (DM) is associated with accelerated cognitive decline. However, the mechanism of diabetic cognitive impairment remains poorly understood. In this study, we found that the expression of Sirtuin 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase, was downregulated significantly in the hippocampus of streptozotocin (STZ)-induced diabetic cognitive impairment rats.

Quercetin attenuates diabetic neuropathic pain by inhibiting mTOR/p70S6K pathway-mediated changes of synaptic morphology and synaptic protein levels in spinal dorsal horn of db/db mice.

Numerous studies indicate that the changes of synaptic morphology and synaptic protein levels in spinal dorsal horn neurons contributes to the development and maintenance of neuropathic pain. Quercetin, a bioflavonoid compound, has been shown to have analgesic effect in several pain models. However, the underlying mechanism for quercetin to allieviate pain is unclear.

SIRT1 Decreases Emotional Pain Vulnerability with Associated CaMKIIα Deacetylation in Central Amygdala.

Emotional disorders are common comorbid conditions that further exacerbate the severity and chronicity of chronic pain. However, individuals show considerable vulnerability to the development of chronic pain under similar pain conditions. In this study on male rat and mouse models of chronic neuropathic pain, we identify the histone deacetylase Sirtuin 1 (SIRT1) in central amygdala as a key epigenetic regulator that controls the development of comorbid emotional disorders underlying the individual vulnerability to chronic pain.

Sirtuin 1 alleviates diabetic neuropathic pain by regulating synaptic plasticity of spinal dorsal horn neurons.

Accumulating evidence has demonstrated that the enhanced synaptic plasticity of nociceptive interneurons in the spinal dorsal horn is the basis of central sensitization in neuropathic pain. Our previous results demonstrated that sirtuin 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, alleviates neuropathic pain in type 2 diabetes mellitus rats. SIRT1 has also been reported to regulate synaptic plasticity in different brain neurons.