0-TESTO COMPLETO.pdf - Fondazione Santa Lucia

Sezione III: Attività per progetti
Behavioral evaluations
The aim of the behavioral testing will be to assess whether decreased
Reelin expression, in combination with gender, and with pre-/post-natal
exposure to different dosages of MeHg is associated with significant alterations
in social motivations and interactions consistent with an autism-like
phenotype.
Analysis of ultrasonic vocalizations in response to separation from the lactating
mother will be used as an index of social motivation and provide a very
sensitive insight on early neurobehavioral alterations. In particular, the analysis
of ultrasonic vocalizations in response to separation from the lactating
mother is an index of social motivation and provides a very sensitive insight
on early emotional alterations [see Cagiano et al. 1986; Santucci et al. 1993], it
represents a behaviourally interesting model of early communication deficits
in autism. It is worth noting that a similar approach has been already used in
a mouse model of language deficit, i.e. mice with a single copy disruption of
the FoxP2 gene, a gene coding for a transcription factor which has been associated
with language impairment in humans. FoxP2 heterozygous mice show
significant alterations in ultrasound vocalization in response to maternal separation
[Shu et al. 2005]. Interestingly, and relevant to our study and previous
data in rl/+ mice, cerebellar abnormalities have been observed in the Foxp2
mutant, and in particular, heterozygous mice show abnormally-placed PCs.
Analyses of ultrasonic vocalizations will be conducted in pups following separation
from the lactating mother. The quality and quantity of the ultrasonic
production will be evaluated at P7 and P11 in at least 4 pups per group. The
pup will be positioned below a Bat detector [Noldus mini-3 bat detector, London
UK] set to 50 kHz in a soundproof chamber maintained at 21-22°. Six
minutes of recording will commence after the pup has habituated to the
chamber for 30 sec. The Noldus Ultravox software program automatically
records and counts the ultrasonic vocalisation events.
Social Interactions. Qualitative and quantitative impairments in social
interaction and the cognitive inflexibility and the upset at changes in routine
and habit are the first defining feature of autism [Crawley 2007]. Analysis of
appropriate social interactions, of the tendency to spend time with another
conspecific, the preference for social novelty are used as an index of sociability
and provide a very sensitive insight into the social deficits in different animal
models of autism. At P21 mice will be tested for social interaction. In this
test the mice of the different groups will be in the center compartment of a
three-chambered Noldus Phenotyper 3000 arena and scored for measures of
nose-to-nose sniffing, anogenital sniffing, following, crawling over/under,
social grooming, self-grooming, exploratory activity.
Assessment of potential mechanisms for determining autistic phenotype
in our three-factor model
At the end of the second year, the data collected will allow to pin point
interactions among environmental (Hg exposure), genetic (reelin haploinsufficiency),
and hormonal (sex) factors in inducing autism-like behaviour and
590 2009