Maternal Insult and Embryonic Neurodevelopmental Damage. Fetal hypoxia. Hava Golan, Mahmoud Huleihel, Ira Kashtuzki-Philip, Maya Gerstein, Revital Mane, Miriam Stilman, Tamar Levav, Vered Kaplan Dept of Developmental Genetics & Zlotowski center for Neuroscience. Energy failure. - PowerPoint PPT Presentation
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Maternal Insult and Embryonic Neurodevelopmental Damage
Hava Golan, Mahmoud Huleihel, Ira Kashtuzki-Philip, Maya Gerstein, Revital Mane, Miriam Stilman, Tamar Levav, Vered Kaplan
Dept of Developmental Genetics & Zlotowski center for Neuroscience
Energy failure
Transcriptional and translational regulation
Fetal hypoxia
RegenerationCell death
Immediate response Delayed response
Animals: Pregnant, Jackson Black C-57 mice at gestation day 17 were assigned to one of four groups:
1. Saline injections (i.p) in room air exposure (S+A), 2. Saline injections (i.p) with hypoxia chamber exposure (S+H), 3. Mg injections (i.p) in room air exposure (Mg+A),4. Mg injections (i.p) with hypoxia chamber exposure (Mg+H).
Study Design
Mg administration: 270 mg/kg followed by 27 mg/kg every 20 minutes for 4 hours. A second loading dose of 270 mg/kg was given at the end of the 4-hour period. Control mice were injected with saline following the same volume and schedule.
P 180P 14P 1
E17 E20E18 P1 P7 P14 P21 P120-P180
4h pretreatmentSaline or Mg2h hypoxia or air
9% O23% CO2
IS MAGNESIUM-SULFATE LOAD A PROPHLACTIC TREATMENT FOR PRENATAL HYPOXIA?
S+H Mg+HBehaviorMotor impaired partial protectionLearning impaired short and long term Sort-term normal long-term not
Brain morphologyCerebellum low PC density PC density normal
thinner granular layer not preventedCortex low cell density L 2-3,5-6 L5-6 protectedHippocampus no effect thinner CA1 layer
GABAergic neuronsCortex PV and CB decreased L2-3, 5-6 L2-3 partial protected Hippocampus PV in CA3 decreased not prevented Inhibitory synaptogenesisCortex not affected increased in all layersHippocapus VGAT in CA3 & hilus decreased not prevented
Glutamatergic synaptogenesisCerebellum reduced NR2AB density in PC at P1 normal NR2AB densityCortex no effect no effectHippocampus reduced NR2AB in all regions at P1 normal NR2AB density
First minute Fifth minute
S+
AS
+H
Mg+
HBehavior - Exploration in open field
Vertical Pole
0
20
40
60
80
100
vertical pole -12 cm vertical pole -18 cm
% o
f m
ice
fai
led
Wire Clinging
0
5
10
15
20
25 Mg+H
S+H
S+A
% o
f m
ice
faile
d
Str
ide
dist
ance
(m
m)
0
10
20
30
40
50
60
70
80
1
Footprint Pattern
0
10
20
30
40
50
S + A
% o
f M
ice
Sto
ppe
d
*
Motor Function
N=11-15 animals in each group Golan et al., 2004
S+A Mg+HS+H
Cerebellum Clb 3
0.0
1.0
2.0
3.0
4.0
5.0
P u r k in je c e lls
S+A
S+H
Mg+H
0
50
100
150
200
250
G r a n u la r la y e r
Gra
nula
r L
ayer
Wid
th (m
)
Pur
kinj
e ce
lls
dens
ity
(cel
l/10
0m
)Morphology - Cerebellum
**
**
N=3-4 animals in each group, 3-4 section per animal Golan et al., 2004