HAL Id: hal-02492831
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Submitted on 27 Feb 2020
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Mimicking schizophrenia symptoms in mice by combining factors: genetic, early environmental stress
and late pharmacological conditioning
Valentine Bouët, Solenn Percelay, Nicole Turnbull, Thomas Freret, Michel Boulouard
To cite this version:
Valentine Bouët, Solenn Percelay, Nicole Turnbull, Thomas Freret, Michel Boulouard. Mimicking schizophrenia symptoms in mice by combining factors: genetic, early environmental stress and late pharmacological conditioning. NeuroFrance, May 2019, Marseille, France. �hal-02492831�
Mimicking schizophrenia symptoms in mice by combining factors:
genetic, early environmental stress and late pharmacological conditioning
Valentine Bouet, Solenn Percelay, Nicole Turnbull, Thomas Freret, Michel Boulouard COMETE, UMR 1075 INSERM/Unicaen
1. Schizophrenia
Frequent psychiatric disease 1%
Multifactorial etiology
Unsatisfactory treatments
Crucial need te refine animal models of schizophrenia
2. Our model
Partial genetic deletion MAP6
Microtubule-Associated Protein 6
Maternal Separation
24h in PND9 pups
Subchronic MK801
0,05 mg/kg, ip, 5 days from PND60
MAP6+/-
Maternal separation MS
MK801
3hit model of schizophrenia mimics :
Positive like symptoms (increased spontaneous activity) Negative like symptoms (decreased social recognition)
Cognitive-like symptoms (decreased working memory performances) 3. Behavior
1hit
MAP6+/-
1hit MS
1hit
MK801 3hit
Openfield
Anova p=0.02
* : Post-hoc Tukey’s test n = 9, 8, 14, 9, 8, respectively
* *
Total distance (cm)
CONT
1hit MA P6
1hit MS
1hit MK 3hit 0
5000 10000 15000 20000 25000
Traveled distance increased in 3hit
MAP6 and MK :
intermediate profiles
No difference in time in the center
Working memory
# #
Kruskal-Wallis, p=0,77
# : univariate t-test ≠ 50%, p<0.05 Alternation %
CON T
1hit MA P6
1hit MS
1hit MK 3hit 0
20 40 60 80 100
Impaired performances in MAP6, MK and 3hit
Increased activity (number or arm entries) in MAP6 and 3hit
Object recognition
1h
# # # #
Kruskal-Wallis, p=0,33
# : univariate t-test ≠ 0, p>0.05 Index : (N-F)/(N+F)
CON T
1hit MA P6
1hit MS
1hit MK 3hit -0.5
0.0 0.5 1.0 1.5
Impaired performances in MK But not evidenced in 3hit
Social behavior
Index : (Full-Empty)/(Full+Empty)
CON T
1hit MA P6
1hit MS
1hit MK 3hit -50
0 50 100
Index : (New-Fam)/(Full+Fam)
CON T
1hit MA P6
1hit MS
1hit MK 3hit -100
-50 0 50 100
# : univariate t-test p>0.05
# #
Social preference not observed in all groups
Social recognition altered in 1hit MAP6, 1hit MK and 3hit
Hyperactivity :
positive-like symptom? Deficit in working memory :
Cognitive deficit No deficit in recognition
memory
Deficit in social recognition : Negative-like symptoms?
Construct validity Face validity
Ongoing : parvalbumin+ neurons To do : predictive validity
