ABSTRACT: Aging-associated inflammatory and oxidative changes in the rat urinary bladder and dorsal root ganglia - preventive effect of caloric restriction [L6 dorsal root ganglia]
Project description:Aging-associated inflammatory and oxidative changes in the rat urinary bladder and dorsal root ganglia - preventive effect of caloric restriction [bladder]
Project description:Aging-associated inflammatory and oxidative changes in the rat urinary bladder and dorsal root ganglia - preventive effect of caloric restriction
Project description:Purpose: To disclose the molecular mechanisms of aging-related functional impairments of the rat bladder, and to determine whether long-term caloric restriction (CR) may have preventive effects on these mechanisms. Materials and Methods: Male Fischer 344 rats were divided into three groups: young (6 months-old) fed ad libitum (Y, N = 16), old (25-28 months-old) fed ad libitum (O+AL, N = 15), and old (25-28 months-old) fed restrictedly three days a week since 6 weeks-old (O+CR, N = 16). cDNA microarray analysis and real-time polymerase chain reaction (RT-PCR) of the bladder and L6 dorsal root ganglia (L6DRG) were performed. The bladder was subjected to oxidative stress measurement and immunohistochemistry. Results: In the O+AL group, 83 genes in the bladder and 48 genes in the L6DRG were up-regulated than compared with those of the Y and O+CR groups (fold change > 2). These genes were mostly related to immune- and inflammatory-responses. Immunohistochemistry showed that Granzyme B, a cytotoxic T-lymphocyte-associated serine protease, and matrix metalloproteinase 13 (Mmp13), an interstitial collagenase, were more strongly expressed in the bladder of the O+AL than the Y and O+CR groups. The level of Malondialdehyde (MDA), an oxidative stress marker, was higher in the O+AL than the Y group, whereas there were no significant differences between the O+CR and Y groups. Conclusions: In the rat, aging is associated with up-regulation of immune and inflammatory genes in the bladder and DRG as well as with oxidative and fibrotic changes of the bladder. Long-time CR reduced these aging-related changes.
Project description:Purpose: To disclose the molecular mechanisms of aging-related functional impairments of the rat bladder, and to determine whether long-term caloric restriction (CR) may have preventive effects on these mechanisms. Materials and Methods: Male Fischer 344 rats were divided into three groups: young (6 months-old) fed ad libitum (Y, N = 16), old (25-28 months-old) fed ad libitum (O+AL, N = 15), and old (25-28 months-old) fed restrictedly three days a week since 6 weeks-old (O+CR, N = 16). cDNA microarray analysis and real-time polymerase chain reaction (RT-PCR) of the bladder and L6 dorsal root ganglia (L6DRG) were performed. The bladder was subjected to oxidative stress measurement and immunohistochemistry. Results: In the O+AL group, 83 genes in the bladder and 48 genes in the L6DRG were up-regulated than compared with those of the Y and O+CR groups (fold change > 2). These genes were mostly related to immune- and inflammatory-responses. Immunohistochemistry showed that Granzyme B, a cytotoxic T-lymphocyte-associated serine protease, and matrix metalloproteinase 13 (Mmp13), an interstitial collagenase, were more strongly expressed in the bladder of the O+AL than the Y and O+CR groups. The level of Malondialdehyde (MDA), an oxidative stress marker, was higher in the O+AL than the Y group, whereas there were no significant differences between the O+CR and Y groups. Conclusions: In the rat, aging is associated with up-regulation of immune and inflammatory genes in the bladder and DRG as well as with oxidative and fibrotic changes of the bladder. Long-time CR reduced these aging-related changes.
Project description:Here we studied the NOX2 dependent redox-proteome in dorsal root ganglia in mice. The overall goal was to assess the degree of NOX2-dependent changes in oxidised proteins following exposure to enriched enviroment and sciatic nerve axotomy in dorsal root ganglia.
Project description:Nociceptors play an essential role in both acute pain and chronic pain conditions. In this study, we examined the proteome of mouse dorsal root ganglia and compared NaV1.8Cre+/-; ROSA26-flox-stop-flox-DTA (Diphtheria toxin fragment A) mutant mice (NaV1.8Cre-DTA), in which NaV1.8-positive neurons (mainly nociceptors) in dorsal root ganglia (DRG) were ablated, with respective littermate wildtype controls.
Project description:FK1706 potentiated nerve growth factor-induced neurite outgrowth, putatively mediated via FKBP-52 and the Ras/Raf/MAPK signaling pathway. It also improved mechanical allodynia accompanied by the recovery of intraepidermal nerve fiber density in a painful diabetic neuropathy in rats. We analyzed gene expression of the dorsal root ganglia together with measurement of mechanical allodynia in diabetic rats to try to capture the global fingerprint of changes in gene expression associated with FK1706 administration and also to elucidate the putative mechanisms of its neurotrophic activity in vivo. Normal, STZ-treated controls, and STZ + FK1706 groups were used to evaluate gene expression analysis. Dorsal root ganglia from L4 to L6 were collected at the day after 1, 2, and 3 weeks of FK1706 administration, were immediately immersed in RNAlater reagent, and stored as instructed before RNA extraction. Equal amounts of total RNA from five rats were collected for each group.
Project description:To investigate mechanisms underlying neuropathic pain, we established sciatic nerve chronic constriction injury (CCI) neuropathic pain model in rats, and performed RNA-seq on ipsilateral bulk L4-L6 dorsal root ganglia from CCI rats and sham rats 11 days after surgery. By comprehensive analysis, we identified several key mRNAs and miRNAs, especially those associated with inflammatory immune response, may serve as promising targets, facilitating further investigation and eventually developing better therapeutic strategies for NP.
