Limits...
IL1RAPL1 knockout mice show spine density decrease, learning deficiency, hyperactivity and reduced anxiety-like behaviours.

Yasumura M, Yoshida T, Yamazaki M, Abe M, Natsume R, Kanno K, Uemura T, Takao K, Sakimura K, Kikusui T, Miyakawa T, Mishina M - Sci Rep (2014)

Bottom Line: Here, we showed that the spine density of cortical neurons was significantly reduced in IL1RAPL1 knockout mice.Furthermore, the behavioural flexibility was slightly reduced in the T-maze test.These results suggest that IL1RAPL1 ablation resulted in spine density decrease and affected not only learning but also behavioural flexibility, locomotor activity and anxiety.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Molecular Neurobiology and Pharmacology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan [2] Liaison Academy, School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.

ABSTRACT
IL-1 receptor accessory protein-like 1 (IL1RAPL1) is responsible for nonsyndromic intellectual disability and is associated with autism. IL1RAPL1 mediates excitatory synapse formation through trans-synaptic interaction with PTPδ. Here, we showed that the spine density of cortical neurons was significantly reduced in IL1RAPL1 knockout mice. The spatial reference and working memories and remote fear memory were mildly impaired in IL1RAPL1 knockout mice. Furthermore, the behavioural flexibility was slightly reduced in the T-maze test. Interestingly, the performance of IL1RAPL1 knockout mice in the rotarod test was significantly better than that of wild-type mice. Moreover, IL1RAPL1 knockout mice consistently exhibited high locomotor activity in all the tasks examined. In addition, open-space and height anxiety-like behaviours were decreased in IL1RAPL1 knockout mice. These results suggest that IL1RAPL1 ablation resulted in spine density decrease and affected not only learning but also behavioural flexibility, locomotor activity and anxiety.

Show MeSH

Related in: MedlinePlus

Increased locomotor activity and decreased anxiety-like behaviour of IL1RAPL1 knockout mice.(A–D) Open field test of wild-type mice (open circles, n = 40) and IL1RAPL1 knockout mice (closed circles, n = 40). Total distance (A), vertical activity (B), stereotypic counts (C), and time spent in center arena (D) were scored in each 5 min period. (E–H) Elevated plus maze test of wild-type mice (white bars, n = 40) and IL1RAPL1 knockout mice (black bars, n = 40). Total distance traveled (E), number of entries into arms (F), percentage of time spent on the open arms (G), and percentage of entries into the open arms (H) were recorded. (I–L) Light/dark transition test of wild-type mice (white bars, n = 40) and IL1RAPL1 knockout mice (black bars, n = 40). Total distance traveled in the light and dark chambers (I), time spent in the light chamber (J), number of light/dark transition (K), and first latency to enter the light chamber (L) were recorded. All values represent as mean ± SEM.* p < 0.05, ** p < 0.01, and *** p < 0.001, respectively; Two-way repeated measures ANOVA followed by Fisher's LSD test (A, C, D) and one-way ANOVA (E–L). The p values indicate genotype effect in two-way repeated measures ANOVA (A, C, D).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4196104&req=5

f7: Increased locomotor activity and decreased anxiety-like behaviour of IL1RAPL1 knockout mice.(A–D) Open field test of wild-type mice (open circles, n = 40) and IL1RAPL1 knockout mice (closed circles, n = 40). Total distance (A), vertical activity (B), stereotypic counts (C), and time spent in center arena (D) were scored in each 5 min period. (E–H) Elevated plus maze test of wild-type mice (white bars, n = 40) and IL1RAPL1 knockout mice (black bars, n = 40). Total distance traveled (E), number of entries into arms (F), percentage of time spent on the open arms (G), and percentage of entries into the open arms (H) were recorded. (I–L) Light/dark transition test of wild-type mice (white bars, n = 40) and IL1RAPL1 knockout mice (black bars, n = 40). Total distance traveled in the light and dark chambers (I), time spent in the light chamber (J), number of light/dark transition (K), and first latency to enter the light chamber (L) were recorded. All values represent as mean ± SEM.* p < 0.05, ** p < 0.01, and *** p < 0.001, respectively; Two-way repeated measures ANOVA followed by Fisher's LSD test (A, C, D) and one-way ANOVA (E–L). The p values indicate genotype effect in two-way repeated measures ANOVA (A, C, D).

Mentions: We examined the locomotor activity and anxiety-like behaviour in the open field, the elevated plus maze and the light/dark transition tests. IL1RAPL1 knockout mice consistently exhibited greater locomotor activity in all of the tasks we examined. Total distances traveled by IL1RAPL1 knockout mice were significantly longer than those of wild-type mice in the open field test (F1, 78 = 8.04, p = 0.006, repeated measures ANOVA) (Fig. 7A), the elevated plus maze test (F1, 78 = 23.5, p < 0.0001, one-way ANOVA) (Fig. 7E), and the light/dark transition test (light, F1, 78 = 4.75, p = 0.03; dark, F1, 78 = 7.74, p = 0.007) (Fig. 7I). In addition, there were significant differences between wild-type and IL1RAPL1 knockout mice in the stereotypic counts in the open field test (F1, 78 = 5.67, p = 0.02, repeated measures ANOVA) (Fig. 7C) and in the number of total entries in the elevated plus maze test (F1, 78 = 18.1, p < 0.0001, one-way ANOVA) (Fig. 7F). Vertical activity in the open field (F1, 78 = 0.16, p = 0.7, repeated measures ANOVA) (Fig. 7B) and the number of transitions in the light–dark transition test (F1, 78 = 0.89, p = 0.3, one-way ANOVA) (Fig. 7K) did not differ between wild-type and IL1RAPL1 knockout mice.


IL1RAPL1 knockout mice show spine density decrease, learning deficiency, hyperactivity and reduced anxiety-like behaviours.

Yasumura M, Yoshida T, Yamazaki M, Abe M, Natsume R, Kanno K, Uemura T, Takao K, Sakimura K, Kikusui T, Miyakawa T, Mishina M - Sci Rep (2014)

Increased locomotor activity and decreased anxiety-like behaviour of IL1RAPL1 knockout mice.(A–D) Open field test of wild-type mice (open circles, n = 40) and IL1RAPL1 knockout mice (closed circles, n = 40). Total distance (A), vertical activity (B), stereotypic counts (C), and time spent in center arena (D) were scored in each 5 min period. (E–H) Elevated plus maze test of wild-type mice (white bars, n = 40) and IL1RAPL1 knockout mice (black bars, n = 40). Total distance traveled (E), number of entries into arms (F), percentage of time spent on the open arms (G), and percentage of entries into the open arms (H) were recorded. (I–L) Light/dark transition test of wild-type mice (white bars, n = 40) and IL1RAPL1 knockout mice (black bars, n = 40). Total distance traveled in the light and dark chambers (I), time spent in the light chamber (J), number of light/dark transition (K), and first latency to enter the light chamber (L) were recorded. All values represent as mean ± SEM.* p < 0.05, ** p < 0.01, and *** p < 0.001, respectively; Two-way repeated measures ANOVA followed by Fisher's LSD test (A, C, D) and one-way ANOVA (E–L). The p values indicate genotype effect in two-way repeated measures ANOVA (A, C, D).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4196104&req=5

f7: Increased locomotor activity and decreased anxiety-like behaviour of IL1RAPL1 knockout mice.(A–D) Open field test of wild-type mice (open circles, n = 40) and IL1RAPL1 knockout mice (closed circles, n = 40). Total distance (A), vertical activity (B), stereotypic counts (C), and time spent in center arena (D) were scored in each 5 min period. (E–H) Elevated plus maze test of wild-type mice (white bars, n = 40) and IL1RAPL1 knockout mice (black bars, n = 40). Total distance traveled (E), number of entries into arms (F), percentage of time spent on the open arms (G), and percentage of entries into the open arms (H) were recorded. (I–L) Light/dark transition test of wild-type mice (white bars, n = 40) and IL1RAPL1 knockout mice (black bars, n = 40). Total distance traveled in the light and dark chambers (I), time spent in the light chamber (J), number of light/dark transition (K), and first latency to enter the light chamber (L) were recorded. All values represent as mean ± SEM.* p < 0.05, ** p < 0.01, and *** p < 0.001, respectively; Two-way repeated measures ANOVA followed by Fisher's LSD test (A, C, D) and one-way ANOVA (E–L). The p values indicate genotype effect in two-way repeated measures ANOVA (A, C, D).
Mentions: We examined the locomotor activity and anxiety-like behaviour in the open field, the elevated plus maze and the light/dark transition tests. IL1RAPL1 knockout mice consistently exhibited greater locomotor activity in all of the tasks we examined. Total distances traveled by IL1RAPL1 knockout mice were significantly longer than those of wild-type mice in the open field test (F1, 78 = 8.04, p = 0.006, repeated measures ANOVA) (Fig. 7A), the elevated plus maze test (F1, 78 = 23.5, p < 0.0001, one-way ANOVA) (Fig. 7E), and the light/dark transition test (light, F1, 78 = 4.75, p = 0.03; dark, F1, 78 = 7.74, p = 0.007) (Fig. 7I). In addition, there were significant differences between wild-type and IL1RAPL1 knockout mice in the stereotypic counts in the open field test (F1, 78 = 5.67, p = 0.02, repeated measures ANOVA) (Fig. 7C) and in the number of total entries in the elevated plus maze test (F1, 78 = 18.1, p < 0.0001, one-way ANOVA) (Fig. 7F). Vertical activity in the open field (F1, 78 = 0.16, p = 0.7, repeated measures ANOVA) (Fig. 7B) and the number of transitions in the light–dark transition test (F1, 78 = 0.89, p = 0.3, one-way ANOVA) (Fig. 7K) did not differ between wild-type and IL1RAPL1 knockout mice.

Bottom Line: Here, we showed that the spine density of cortical neurons was significantly reduced in IL1RAPL1 knockout mice.Furthermore, the behavioural flexibility was slightly reduced in the T-maze test.These results suggest that IL1RAPL1 ablation resulted in spine density decrease and affected not only learning but also behavioural flexibility, locomotor activity and anxiety.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Molecular Neurobiology and Pharmacology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan [2] Liaison Academy, School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.

ABSTRACT
IL-1 receptor accessory protein-like 1 (IL1RAPL1) is responsible for nonsyndromic intellectual disability and is associated with autism. IL1RAPL1 mediates excitatory synapse formation through trans-synaptic interaction with PTPδ. Here, we showed that the spine density of cortical neurons was significantly reduced in IL1RAPL1 knockout mice. The spatial reference and working memories and remote fear memory were mildly impaired in IL1RAPL1 knockout mice. Furthermore, the behavioural flexibility was slightly reduced in the T-maze test. Interestingly, the performance of IL1RAPL1 knockout mice in the rotarod test was significantly better than that of wild-type mice. Moreover, IL1RAPL1 knockout mice consistently exhibited high locomotor activity in all the tasks examined. In addition, open-space and height anxiety-like behaviours were decreased in IL1RAPL1 knockout mice. These results suggest that IL1RAPL1 ablation resulted in spine density decrease and affected not only learning but also behavioural flexibility, locomotor activity and anxiety.

Show MeSH
Related in: MedlinePlus