The effect of chronic prenatal hypoxia on the development of mature neurons in the cerebellum

Journal of Neurodevelopmental Disorders

Yonghyun Jeon²  Eunyoung Kim³  Hyunyoung Lee¹  Yoonyoung Chung²  Keumyoung So¹ 

[1] Department of Anesthesiology and Pain medicine, Chosun University Hospital, 375 Seosuk-dong, Dong-Gu, Gwangju 501-759, Korea;Department of Anatomy, School of Medicine, Chosun University, 375 Seosuk-dong, Dong-Gu, Gwangju 501-759, Korea;Department of pediatrics, Chosun University Hospital, 375 Seosuk-dong, Dong-Gu, Gwangju 501-759, Korea

关键词: Guinea pig;    Cerebellum;    Hypoxia;   

Others  :  806273
DOI  :  10.1186/1866-1955-5-17

 received in 2013-01-03, accepted in 2013-06-24,  发布年份 2013

【 摘 要 】

Background

Adverse intrauterine circumstances can result in abnormal brain development, and can contribute to many neurological disorders such as cerebral palsy and cognitive and behavioral deficits. These neurological problems are caused by conditions that cause chronic placental insufficiency (CPI), such as hypoxia and acidemia. Hypoxia has been implicated in structural alterations of the cerebellum during development; however, the changes to the cerebellar external granular layer (EGL) induced by chronic prenatal hypoxia are not well understood. We therefore investigated the effect of chronic prenatal hypoxia on the development of mature neurons in the EGL using the guinea pig CPI model.

Methods

Unilateral uterine artery ligation was performed at 30 to 32 days of gestation (dg) - with term defined as approximately 67 dg. At 50 dg, 60 dg, and one week after birth, fetuses and newborns were sacrificed and assigned to either the growth-restricted (GR) or control (no ligation) group. After fixation, dissection, and sectioning of cerebellar tissue from these animals, immunohistochemistry was performed with antibodies raised to hypoxia-induced factor 1α (Hif1α), Pax6, NeuroD, and NeuN.

Results

The induction of hypoxia was confirmed by the presence of Hif1α immunoreactivity in the EGL of the GR (but not control) fetuses. The only other cellular immunoreactivity found in any of the tissues was to the NeuN antibody, which is a marker of mature neurons. The proportion of NeuN-immunoreactive (NeuN-IR) cells to the total number of cells in the EGL did not differ between the GR and control groups at 50 and 60 dg. The density of NeuN-IR cells was greater in GR fetuses than in controls at 60 dg (P < 0.05) but not at 50 dg. At one week after birth, the EGL was just one cell thick, and only a few NeuN-IR cells could be observed in both groups. TUNEL assays performed to enable the evaluation of apoptosis in the cerebellar EGL revealed that cell death was not affected by hypoxia at 50 dg, 60 dg, and one week after birth.

Conclusion

These findings indicate that chronic prenatal hypoxia affects the process of neuronal production late in fetal life, but that this effect does not persist postnatally.

【 授权许可】

   
2013 So et al.; licensee BioMed Central Ltd.

【 图 表 】

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