Our group has recently reported enhanced lipid oxidative stress (OS) in blood samples from girls with Rett syndrome (RTT) in its various clinical presentations and progression stages (1-5). To date, no information regarding OS status in the RTT mouse models is available. Our aim was to verify whether OS damage is conserved in the brain from two common RTT mouse models (Bird's MeCP2 null, y/-, and MeCP2 308 truncated). Brain tissue from n=10 MeCP2 null (n=4 fully symptomatic, n=3 pre-symptomatic and n=3 early symptomatic males) MeCP2 308 truncated (n=10 heterozygous females) mice were examined. Control animals (wt) were also assayed (n= 15 wt for comparison of MeCP2 null, and n=10 wt for comparison of MeCP2 308 truncated). Brain tissues were homogenized and F2-IsoPs, F4-NeuroPs, F3-IsoPs and F2-dihomo-IsoPs were measured, as well as NPBI content. IsoPs were measured by GC-NICI/MS-MS and NPBI by HPLC. As for NPBI in MeCP2 308 mice, samples had to be pooled and only n=2 is currently available. F2-IsoPs and F4-Neurops were significantly increased in the brain from fully symptomatic, pre-symptomatic and early symptomatic MeCP2 null mice as well as in the MeCP2 308 truncated heterozygous females. Differences in F2-dihomo-IsoPs between MeCP2 308 and wt just missed statistical significance (p < 0.08). NPBI content was significantly increased in fully symptomatic and pre-symptomatic MeCP2 null mice, and a similar trend was evident in MeCP2 308 mice. Conversely, no significant changes were observed for F3-IsoPs. These results indicate that significant lipid OS damage is occurring in the brain of the examined RTT mouse models, and primarily involves gray matter (i.e., neurons). In the null mouse OS damage in the brain is detectable well before the onset of symptoms (by about 5 weeks) and is still evident in the early symptomatic phase. Even if so far scarcely investigated, lipid brain OS damage is a relevant feature in RTT mouse models, thus confirming previous data from RTT patients (typical and early seizure variant).
Early oxidative damage in Rett mouse brain
Filosa S;Della Ragione F;D'Esposito M
2011
Abstract
Our group has recently reported enhanced lipid oxidative stress (OS) in blood samples from girls with Rett syndrome (RTT) in its various clinical presentations and progression stages (1-5). To date, no information regarding OS status in the RTT mouse models is available. Our aim was to verify whether OS damage is conserved in the brain from two common RTT mouse models (Bird's MeCP2 null, y/-, and MeCP2 308 truncated). Brain tissue from n=10 MeCP2 null (n=4 fully symptomatic, n=3 pre-symptomatic and n=3 early symptomatic males) MeCP2 308 truncated (n=10 heterozygous females) mice were examined. Control animals (wt) were also assayed (n= 15 wt for comparison of MeCP2 null, and n=10 wt for comparison of MeCP2 308 truncated). Brain tissues were homogenized and F2-IsoPs, F4-NeuroPs, F3-IsoPs and F2-dihomo-IsoPs were measured, as well as NPBI content. IsoPs were measured by GC-NICI/MS-MS and NPBI by HPLC. As for NPBI in MeCP2 308 mice, samples had to be pooled and only n=2 is currently available. F2-IsoPs and F4-Neurops were significantly increased in the brain from fully symptomatic, pre-symptomatic and early symptomatic MeCP2 null mice as well as in the MeCP2 308 truncated heterozygous females. Differences in F2-dihomo-IsoPs between MeCP2 308 and wt just missed statistical significance (p < 0.08). NPBI content was significantly increased in fully symptomatic and pre-symptomatic MeCP2 null mice, and a similar trend was evident in MeCP2 308 mice. Conversely, no significant changes were observed for F3-IsoPs. These results indicate that significant lipid OS damage is occurring in the brain of the examined RTT mouse models, and primarily involves gray matter (i.e., neurons). In the null mouse OS damage in the brain is detectable well before the onset of symptoms (by about 5 weeks) and is still evident in the early symptomatic phase. Even if so far scarcely investigated, lipid brain OS damage is a relevant feature in RTT mouse models, thus confirming previous data from RTT patients (typical and early seizure variant).I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
