Cerebellar brain-derived neurotrophic factor, nerve growth factor, and neurotrophin-3 expression in male and female rats is differentially affected by hypergravity exposure during discrete developmental periods.
We previously reported that the effects of perinatal exposure to hypergravity on cerebellum and motor functions in rat neonates are strongly dependent on the specific developmental period of exposure. In the present study, we explored the hypothesis that neurodevelopmental changes are associated with altered expression of brain neurotrophins critical for normal brain growth and differentiation. We compared the effects of hypergravity exposure during four developmental periods: period I extended from gestational day (G) 8 through G15; period II from G15 to birth, period III from birth to postnatal day (P) 6; and period IV extended from G8-P12. For comparison we used stationary control (SC) neonates not exposed to hypergravity. Neurotrophins, brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophin 3 (NT-3) levels were measured in cerebellar homogenates prepared from postnatal day 12 male and female rat neonates using specific ELISAs. Hypergravity exposure affected individual neurotrophins differently and the effect was further determined by the period of hypergravity exposure. ANOVA showed: (1) a significant effect of the period of exposure to hypergravity on cerebellar BDNF (p = 0.009), with maximal decrease of 28.7% in males and 32.1% in females following exposure during period III; (2) a significant effect on NGF (p < 0.0001), with maximal decrease of 35.6% in male and 48.8% in female neonates following exposure during period III; (3) no statistically significant effect on NT-3 expression with a trend towards decreased expression in female rats following exposure during period IV. Although the molecular mechanisms underlying the differential neurotrophins' response to hypergravity are not clear, an altered pattern of their expression is likely to contribute to neurodevelopmental changes and impaired sensorimotor behavior in exposed neonates.
Sajdel-Sulkowska
Elizabeth M
EM
Department of Psychiatry, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA. esulkowska@rics.bwh.harvard.edu
Xu
Ming
M
Koibuchi
Noriyuki
N
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002531:Cerebellum / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D018471:Hypergravity; D008297:Male; D009043:Motor Activity / Q000502:physiology; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D020933:Neurotrophin 3 / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000502:physiology; D045442:Rotarod Performance Test / Q000379:methods; D012727:Sex Characteristics
D019208:Brain-Derived Neurotrophic Factor; D020933:Neurotrophin 3; D020932:Nerve Growth Factor