Twitch properties during electrical stimulation.

<p>Force (A), MRTD (B) and HRT (C) measured simultaneously with MRS acquisition during 6 min stimulation protocol. From 2 min 45 s onwards LCRs had significantly lower twitch force compared to HCRs (p≤0.05). The MRTD values were significantly lower in LCRs compared to HCRs from 2 min 30 s onwards (p≤0.05). LCRs had higher HRT than HCRs throughout the stimulation protocol (p≤0.05). Values are expressed as mean ± SEM.</p

Schematic representation of the setup for measuring rat triceps surae muscle complex function with MR investigation.

<p>Triceps surae contractions were induced indirectly via electrical stimulation at the heel and knee levels. Muscle performance was measured with a force transducer which was attached to the pedal. Information about the leg position was acquired with a ¹H-MR surface coil and muscle metabolic functions were studied with ³¹P-MRS surface coil.</p

PCr, Pi and pH levels during ³¹P-MRS acquisition protocol.

<p>PCr (A), Pi (B) and pH (C) levels in triceps surae muscle complex during stimulation (6 min) and recovery (8 min) measurements. PCr resynthesis was significantly slower in LCRs compared to HCRs (p<0.05) when comparing the individual slope values. LCRs also had significantly lower PCr level in time point 2 min (p<0.05). There were no statistical differences between HCR and LCR groups in Pi levels. Intramuscular pH was lower in LCRs throughout the protocol except for the time points 1 and 9 min. Values are expressed as mean ± SEM.</p

Comparison of initial and end values of the twitch properties.

<p>Initial values of twitch force, MRTD and HRT from First epoch (0–15 s) and from Last epoch (345–360 s) during the electrical stimulation. Values are expressed as mean ± SEM.</p

Rate of change in twitch properties.

<p>The rates of change in relative (% of maximal) twitch force and MRTD in individual time-intervals (100 twitches) during the electrical stimulation. Values are expressed as mean ± SEM.</p

Initial and end values of the twitch properties.

<p>The mean twitch force curves from initial epoch (0–15 s) (A) and from last epoch (345–360 s) (B) during electrical stimulation. The corresponding twitch property values are presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0048345#pone-0048345-t001" target="_blank">Table 1</a>. LCRs seemed to have slightly higher initial maximal twitch force and MRTD (n.s.). At the end of the stimulation protocol LCRs showed significantly lower maximal twitch force and MRTD compared to LCRs (p<0.05). LCRs had significantly higher HRT values both in first and last epoch (p<0.01) than HCRs.</p

Genetic Deletion of Transglutaminase 2 Does Not Rescue the Phenotypic Deficits Observed in R6/2 and zQ175 Mouse Models of Huntington's Disease

<div><p>Huntington's disease (HD) is an autosomal dominant, progressive neurodegenerative disorder caused by expansion of CAG repeats in the huntingtin gene. Tissue transglutaminase 2 (TG2), a multi-functional enzyme, was found to be increased both in HD patients and in mouse models of the disease. Furthermore, beneficial effects have been reported from the genetic ablation of TG2 in R6/2 and R6/1 mouse lines. To further evaluate the validity of this target for the treatment of HD, we examined the effects of TG2 deletion in two genetic mouse models of HD: R6/2 CAG 240 and zQ175 knock in (KI). Contrary to previous reports, under rigorous experimental conditions we found that TG2 ablation had no effect on either motor or cognitive deficits, or on the weight loss. In addition, under optimal husbandry conditions, TG2 ablation did not extend R6/2 lifespan. Moreover, TG2 deletion did not change the huntingtin aggregate load in cortex or striatum and did not decrease the brain atrophy observed in either mouse line. Finally, no amelioration of the dysregulation of striatal and cortical gene markers was detected. We conclude that TG2 is not a valid therapeutic target for the treatment of HD.</p></div

Mean number of days required to obtain 40 reinforcers across two consecutive sessions during the training phase (n = 6–12 per genotype).

<p>*Significant HD genotype effect. WT: wild-type, TG2−/−: homozygous TG2 knockout, HET: zQ175 HET.</p

Reversal phase of the procedural T–maze task (platform location switched; n = 11–12 per genotype).

<p>WT: wild-type, TG2−/−: homozygous TG2 knockout, HET: zQ175 HET, HOM: zQ175 HOM.</p

Reversal phase of the procedural T–maze task (platform location switched; n = 19–24 per genotype).

<p>The graph shows the mean (±SEM) percent correct for each group, on each test day. WT: wild-type, TG2+/−: heterozygous TG2 knockout, TG2−/−: homozygous TG2 knockout.</p