Fig. 2
IKK2-CAPLP−CreERT2 mice develop neurological deficits and show decreased motoric learning. a IKK2-CAPLP−CreERT2 mice exhibit an increased neurological severity score (NSS) over the time course of 40 weeks, peaking at 3 to 4 wpi. b 9 training trials on the rotarod on 3 consecutive days (3 trials per day) immediately after tamoxifen withdrawal show no difference in rotarod performance between IKK2-CAPLP−CreERT2 and control littermates. c Constant NF-κB activation in OLs significantly affects rotarod performance. At 20 wpi, IKK2-CAPLP−CreERT2 animals show a significantly decreased latency to fall off the rotarod, when first trained at this timepoint. Furthermore, animals do not improve with trial number within the 9 trials on 3 consecutive days (3 trials per day) compared to controls. d and e Constant training attenuates motor deficits in IKK2-CAPLP−CreERT2 mice. Mice were either introduced right after transgene induction and then trained for 20 weeks bi-weekly in the beam walking test (“trained”) or introduced to the beam walking test at 20 wpi (“untrained”). No differences were found in easier tasks like crossing the 12 mm square and 17 mm round beam. Untrained and trained control and IKK2-CAPLP−CreERT2 mice mastered the beam walking task in comparable times (untrained: 12 mm: Control: 8 ± 0.9 s, IKK2-CAPLP−CreERT2: 16 ± 1.2 s, 17 mm: Control: 9 ± 1.3 s, IKK2-CAPLP−CreERT2: 14 ± 1.1 s, trained: 12 mm: Control: 15 ± 2.0 s, IKK2-CAPLP−CreERT2: 26 ± 5.3 s, 17 mm: Control: 18 ± 2.6 s, IKK2-CAPLP−CreERT2: 32 ± 6.5 s, n = 7–10). For smaller and therefore more difficult beams, 5 mm square or 11 mm round beam, untrained IKK2-CAPLP−CreERT2 animals take significantly longer to cross the beam than untrained control mice. Crossing times of trained and untrained controls are similar. Trained IKK2-CAPLP−CreERT2 animals cross the 5 mm beam in significantly less time compared to untrained IKK2-CAPLP−CreERT2 animals, no difference was found between trained control and IKK2-CAPLP−CreERT2 animals on the 11 mm beam (untrained: 5 mm: Control: 23 ± 2.9 s, IKK2-CAPLP−CreERT2: 111 ± 8.9 s, 11 mm: Control: 12.5 ± 1.5 s, IKK2-CAPLP−CreERT2: 87.5 ± 17.2 s, trained: 5 mm: Control: 25 ± 3.3 s, IKK2-CAPLP−CreERT2: 61.1 ± 17.3 s, 11 mm: Control: 21.6 ± 3.4 s, IKK2-CAPLP−CreERT2: 49.3 ± 14.8 s, n = 7–10). f and g The ladderwalk test revealed distinct motoric deficits 20 wpi. IKK2-CAPLP−CreERT2 animals showed significantly more missteps in the irregular as well as in the regular ladderwalk there to even greater extent. Missteps are mainly shown in the hindlimbs (irregular: all limbs: Control: 8.0 ± 0.38 missteps, IKK2-CAPLP−CreERT2: 10.3 ± 0.84 missteps, front limbs: Control: 5.3 ± 0.35 missteps, IKK2-CAPLP−CreERT2: 5.1 ± 0.23 missteps, hind limbs: Control: 2.7 ± 0.27 missteps, IKK2-CAPLP−CreERT2: 5.3 ± 0.77 missteps, regular: all limbs: Control: 10.7 ± 0.74 missteps, IKK2-CAPLP−CreERT2: 15.8 ± 0.46 missteps, front limbs: Control: 8.7 ± 0.87 missteps, IKK2-CAPLP−CreERT2: 10.4 ± 0.75 missteps, hind limbs: Control: 2.0 ± 0.30 missteps, IKK2-CAPLP−CreERT2: 5.4 ± 0.70 missteps, n = 8–10). h Grip strength was measured up to 17 wpi revealing significantly decreased grip strength in IKK2-CAPLP−CreERT2 mice. Data are shown as mean ± SEM. Black dots/grey bars, control; red dots/bars, IKK2-CAPLP−CreERT2; striped bars: untrained controls and IKK2-CAPLP−CreERT2. Statistical analysis: Two-way ANOVA multiple comparison test followed by Bonferroni´s post hoc test (*p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001 NS, non-significant (p > 0.05))