Increased NRSF/REST in anterior cingulate cortex contributes to diabetes-related neuropathic pain

High glucose and palmitic acid induces neuronal senescence by NRSF/REST elevation and the subsequent mTOR-related autophagy suppression

“…In the present study, we demonstrated that the elevation of transcriptional regulator NRSF/REST plays an important role in mediating the process of neuronal senescence under HGP treatment. These results further support our previous findings that HGP-induced upregulation of NRSF/REST contributes to the aggravated neuronal activity loss and the enhanced LDH production after HGP [ 13 ]. Previous studies found that NRSF/REST participates in the differentiation and development of neurons [ 27 ], regulates synaptic plasticity [ 28 ], maintains the self-renewal ability of neural stem cells and is also considered to be an oncogene in neurological tumor [ 29 , 30 ].…”

“…Therefore, our results confirmed that like adipose and pancreas, the cellular senescence in the central neurons is also apparent under diabetes-like conditions. Within the present study, we have established an in vitro diabetes model in line with previous studies [ 13 ]. It is worth noting that the HGP treatment cannot fully simulate the in vivo diabetic environment and that this model needs to be further verified for relevance to the in vivo situation.…”

High glucose and palmitic acid induces neuronal senescence by NRSF/REST elevation and the subsequent mTOR-related autophagy suppression

“…In the present study, we demonstrated that the elevation of transcriptional regulator NRSF/REST plays an important role in mediating the process of neuronal senescence under HGP treatment. These results further support our previous findings that HGP-induced upregulation of NRSF/REST contributes to the aggravated neuronal activity loss and the enhanced LDH production after HGP [ 13 ]. Previous studies found that NRSF/REST participates in the differentiation and development of neurons [ 27 ], regulates synaptic plasticity [ 28 ], maintains the self-renewal ability of neural stem cells and is also considered to be an oncogene in neurological tumor [ 29 , 30 ].…”

“…Therefore, our results confirmed that like adipose and pancreas, the cellular senescence in the central neurons is also apparent under diabetes-like conditions. Within the present study, we have established an in vitro diabetes model in line with previous studies [ 13 ]. It is worth noting that the HGP treatment cannot fully simulate the in vivo diabetic environment and that this model needs to be further verified for relevance to the in vivo situation.…”

Knockdown of NRSF Alleviates Ischemic Brain Injury and Microvasculature Defects in Diabetic MCAO Mice

“…Here, we intra-hippocampally injected NRSF shRNA (sh-NRSF) in the DM + MCAO mice to knockdown the expression of NRSF at 1 week after the hyperglycemia onset and performed the MCAO surgery at 1 month after the hyperglycemia onset. As shown in Figures 6A-G, the green fluorescence of sh-NRSF precisely localized in the ipsilateral hippocampus and effectively knocked down the NRSF expression, which coincides with our previous study (24). By whole-brain clearing, we semi-manually determined the identity of the hippocampus and assessed hippocampal volume by Imaris Surface algorithm.…”

“…Studies reported that brain NRSF is elevated after cerebral ischemia (18)(19)(20)(21). We also found that diabetes induces NRSF expression elevation in our previous studies (23,24). In this study, we clarified that the expression of NRSF and its corepressors are further elevated in hippocampus in diabetic ischemia compared with non-diabetic ischemia.…”

“…We previously reported that NRSF elevation participates in neuronal injury under hyperglycemia environment (24), and then we detected NRSF levels in the MCAO and DM + MCAO mice by using the immunofluorescent staining in the present study. As shown in Figure 5A, the NRSF fluorescent particle was obviously increased in the hippocampus of the MCAO mice, and further enhanced in the DM + MCAO mice.…”

High glucose and palmitic acid induces neuronal senescence by NRSF/REST elevation and the subsequent mTOR-related autophagy suppression

“…In the present study, we demonstrated that the elevation of transcriptional regulator NRSF/REST plays an important role in mediating the process of neuronal senescence under HGP treatment. These results further support our previous findings that HGP-induced upregulation of NRSF/REST contributes to the aggravated neuronal activity loss and the enhanced LDH production after HGP [ 13 ]. Previous studies found that NRSF/REST participates in the differentiation and development of neurons [ 27 ], regulates synaptic plasticity [ 28 ], maintains the self-renewal ability of neural stem cells and is also considered to be an oncogene in neurological tumor [ 29 , 30 ].…”

“…Therefore, our results confirmed that like adipose and pancreas, the cellular senescence in the central neurons is also apparent under diabetes-like conditions. Within the present study, we have established an in vitro diabetes model in line with previous studies [ 13 ]. It is worth noting that the HGP treatment cannot fully simulate the in vivo diabetic environment and that this model needs to be further verified for relevance to the in vivo situation.…”

Knockdown of NRSF Alleviates Ischemic Brain Injury and Microvasculature Defects in Diabetic MCAO Mice

“…Here, we intra-hippocampally injected NRSF shRNA (sh-NRSF) in the DM + MCAO mice to knockdown the expression of NRSF at 1 week after the hyperglycemia onset and performed the MCAO surgery at 1 month after the hyperglycemia onset. As shown in Figures 6A-G, the green fluorescence of sh-NRSF precisely localized in the ipsilateral hippocampus and effectively knocked down the NRSF expression, which coincides with our previous study (24). By whole-brain clearing, we semi-manually determined the identity of the hippocampus and assessed hippocampal volume by Imaris Surface algorithm.…”

“…Studies reported that brain NRSF is elevated after cerebral ischemia (18)(19)(20)(21). We also found that diabetes induces NRSF expression elevation in our previous studies (23,24). In this study, we clarified that the expression of NRSF and its corepressors are further elevated in hippocampus in diabetic ischemia compared with non-diabetic ischemia.…”

“…We previously reported that NRSF elevation participates in neuronal injury under hyperglycemia environment (24), and then we detected NRSF levels in the MCAO and DM + MCAO mice by using the immunofluorescent staining in the present study. As shown in Figure 5A, the NRSF fluorescent particle was obviously increased in the hippocampus of the MCAO mice, and further enhanced in the DM + MCAO mice.…”

High glucose and palmitic acid induces neuronal senescence by NRSF/REST elevation and the subsequent mTOR-related autophagy suppression

“…In the present study, we demonstrated that the elevation of transcriptional regulator NRSF/REST plays an important role in mediating the process of neuronal senescence under HGP treatment. These results further support our previous findings that HGP-induced upregulation of NRSF/REST contributes to the aggravated neuronal activity loss and the enhanced LDH production after HGP [ 13 ]. Previous studies found that NRSF/REST participates in the differentiation and development of neurons [ 27 ], regulates synaptic plasticity [ 28 ], maintains the self-renewal ability of neural stem cells and is also considered to be an oncogene in neurological tumor [ 29 , 30 ].…”

“…Therefore, our results confirmed that like adipose and pancreas, the cellular senescence in the central neurons is also apparent under diabetes-like conditions. Within the present study, we have established an in vitro diabetes model in line with previous studies [ 13 ]. It is worth noting that the HGP treatment cannot fully simulate the in vivo diabetic environment and that this model needs to be further verified for relevance to the in vivo situation.…”

Knockdown of NRSF Alleviates Ischemic Brain Injury and Microvasculature Defects in Diabetic MCAO Mice

“…Here, we intra-hippocampally injected NRSF shRNA (sh-NRSF) in the DM + MCAO mice to knockdown the expression of NRSF at 1 week after the hyperglycemia onset and performed the MCAO surgery at 1 month after the hyperglycemia onset. As shown in Figures 6A-G, the green fluorescence of sh-NRSF precisely localized in the ipsilateral hippocampus and effectively knocked down the NRSF expression, which coincides with our previous study (24). By whole-brain clearing, we semi-manually determined the identity of the hippocampus and assessed hippocampal volume by Imaris Surface algorithm.…”

“…Studies reported that brain NRSF is elevated after cerebral ischemia (18)(19)(20)(21). We also found that diabetes induces NRSF expression elevation in our previous studies (23,24). In this study, we clarified that the expression of NRSF and its corepressors are further elevated in hippocampus in diabetic ischemia compared with non-diabetic ischemia.…”

“…We previously reported that NRSF elevation participates in neuronal injury under hyperglycemia environment (24), and then we detected NRSF levels in the MCAO and DM + MCAO mice by using the immunofluorescent staining in the present study. As shown in Figure 5A, the NRSF fluorescent particle was obviously increased in the hippocampus of the MCAO mice, and further enhanced in the DM + MCAO mice.…”