1. Dim light at night affects social behavior in a mouse model of autism
Huei-Bin Wang, Risihika Singh, Dawn H Loh, Christopher S Colwell
Department of Psychiatry and Biobehavioral Sciences, University of California - Los Angeles
Introduction
Impaired
Communication
Stereotype
Behaviors
Impaired
Social
Interaction
Autism
Spectrum
Disorders
• 50-80% patients with ASD
suffer from sleep
disturbances1
• Many ASD patients spend
prolonged time in front of
electrical screens at night2
Cntnap2 KO mice3:
• Mutation of contactin
associated protein 2
(CNTNAP2 / CASPR2), a
member of the neurexin
superfamily
• Social deficits
• Impaired communicatoin
• Repetitive behavior
• We observed reduced rhythm
strength and increased
fragmentation in wheel running
activity of Cntnap2 KO mice.
Figure 1. Separate cohorts of WT and Cntnap2 KO mice were either housed in normal LD, or subjected to DLaN for 2 weeks. Activity was
recorded by using IR sensors. Black shading represents completely darkness. Gray shading represents dim light. In the results, reduced tau
and power were observed in both genotypes. Increased daytime activity was observed without reaching significance.
Conclusions
• DLaN disrupts the daily rhythm in locomotor activity in
both WT and Cntnap2 KO mice.
• Grooming and social preference behavior are selectively
affected in Cntnap2 KO mice by DLaN.
• Social recognition/memory is unaffected by DLaN.
• Our study suggests that sleep hygiene should be an
important intervention to benefit autism subjects.
DLaN affects daily activity rhythms
*P<0.05 between LD and DLaN
#P<0.05 between genotypes
1
No deficits of social recognition in
Cntnap2 KO mice
Figure 4. Following the social preference test, a new
stranger mouse was placed in the empty cup (novel object
in previous test). The subject mouse was re-introduced
and allowed to choose between the familiar and novel
mice for 10 mins. Chamber dwell time and sniffing scoring
were measured as for the social preference test. No
deficits of social recognition were observed due to either
treatment or genotype (2 way ANOVA, P > 0.2).
4
1. Cohen, S., et al. Journal of Neurodevelopmental Disorders,
2014. 6(1): p. 44.
2. Engelhardt, C.R., M.O. Mazurek, and K. Sohl. Pediatrics,
2013. 132(6): p. 1081-9.
3. Penagarikano, O., et al. Cell, 2011. 147(1):235-46.
Reference
(ASD)
Selectively increased repetitive
behavior in Cntnap2 KO mice
*P<0.05 between LD and DLaN
#P<0.05 between genotypes
Figure 2. Mice were allowed to explore an empty arena for
10 mins during the early night (ZT 14 – 16). Both genotypes
subjected to DLaN had increased average time of grooming;
however, the increase of grooming was significant only in
Cntnap2 KO mice. Within DLaN treatment, further analysis
suggested a trend that Cntnap2 KO mice with more daytime
activity had more severe repetitive behavior. This trend was
not observed in WT mice.
2
Selectively reduced social behavior in
Cntnap2 KO mice
*P<0.05 between LD and DLaN
3
Figure 3. In the three chamber social preference test, the subject mouse was
allowed to choose between a novel mouse and a novel object (metal cup) for
10 mins. Time spent in each chamber was recorded automatically. Social
preference index is determined by the ratio of time spent with the novel mouse
normalized to the total time spent in both chambers (novel mouse and novel
object). Sniffing time was scored by two independent scorers watching the
recorded videos. Cntnap2 KO mice housed in DLaN spent significantly less
time in the novel mouse chamber (2 way ANOVA lighting condition P < 0.05,
post hoc results indicated in figure as *).
𝑆𝑛𝑖𝑓𝑓𝑖𝑛𝑔 𝑡𝑖𝑚𝑒 𝑜𝑛 𝑛𝑜𝑣𝑒𝑙 𝑚𝑜𝑢𝑠𝑒 𝑐𝑢𝑝
𝑆𝑛𝑖𝑓𝑓𝑖𝑛𝑔 𝑡𝑖𝑚𝑒 𝑜𝑛 𝑏𝑜𝑡ℎ 𝑐𝑢𝑝𝑠Index =
𝑇𝑖𝑚𝑒 𝑠𝑝𝑒𝑛𝑡 𝑖𝑛 𝑛𝑜𝑣𝑒𝑙 𝑚𝑜𝑢𝑠𝑒 𝑐ℎ𝑎𝑚𝑏𝑒𝑟
𝑇𝑖𝑚𝑒 𝑠𝑝𝑒𝑛𝑡 𝑖𝑛 𝑏𝑜𝑡ℎ 𝑐ℎ𝑎𝑚𝑏𝑒𝑟𝑠Index =
Hypothesis:
Disruption of sleep and
circadian rhythms by dim light at
night may worsen behavioral
symptoms in Cntnap2 KO mice.
Experimental Design:
LD
DLaN
Light Dark
* test
Light Dim Light
* test
Mice were housed for 2 weeks under
either control (light:dark, LD) or dim
light at night (DLaN, 5 lux) conditions.
Behavioral tests to determine repetitive
(grooming) and social behavior were
performed in the early night (ZT 14-16). Acknowledgements
Funding provided by Takeda Pharmaceutical Company