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Prenatal Hypoxia in Different Periods of Embryogenesis Differentially Affects Cell Migration, Neuronal Plasticity, and Rat Behavior in Postnatal Ontogenesis.

Vasilev DS, Dubrovskaya NM, Tumanova NL, Zhuravin IA - Front Neurosci (2016)

Bottom Line: In control rat pups a majority of cells labeled on E14 were localized in the lower cortical layers V-VI while the cells labeled on E18 were mainly found in the superficial cortical layers II-III.In rat pups subjected to hypoxia on E18, the total number of labeled cells in the parietal cortex was also decreased but the number of scattered labeled neurons was higher in the lower cortical layers.Hypoxia on E18 does not significantly affect cortical structure and parietal cortex-dependent behavioral tasks.

View Article: PubMed Central - PubMed

Affiliation: I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of SciencesSaint Petersburg, Russia; Research Center, Saint-Petersburg State Pediatric Medical UniversitySaint Petersburg, Russia.

ABSTRACT
Long-term effects of prenatal hypoxia on embryonic days E14 or E18 on the number, type and localization of cortical neurons, density of labile synaptopodin-positive dendritic spines, and parietal cortex-dependent behavioral tasks were examined in the postnatal ontogenesis of rats. An injection of 5'ethynyl-2'deoxyuridine to pregnant rats was used to label neurons generated on E14 or E18 in the fetuses. In control rat pups a majority of cells labeled on E14 were localized in the lower cortical layers V-VI while the cells labeled on E18 were mainly found in the superficial cortical layers II-III. It was shown that hypoxia both on E14 and E18 results in disruption of neuroblast generation and migration but affects different cell populations. In rat pups subjected to hypoxia on E14, the total number of labeled cells in the parietal cortex was decreased while the number of labeled neurons scattered within the superficial cortical layers was increased. In rat pups subjected to hypoxia on E18, the total number of labeled cells in the parietal cortex was also decreased but the number of scattered labeled neurons was higher in the lower cortical layers. It can be suggested that prenatal hypoxia both on E14 and E18 causes a disruption in neuroblast migration but with a different outcome. Only in rats subjected to hypoxia on E14 did we observe a reduction in the total number of pyramidal cortical neurons and the density of labile synaptopodin-positive dendritic spines in the molecular cortical layer during the first month after birth which affected development of the cortical functions. As a result, rats subjected to hypoxia on E14, but not on E18, had impaired development of the whisker-placing reaction and reduced ability to learn reaching by a forepaw. The data obtained suggest that hypoxia on E14 in the period of generation of the cells, which later differentiate into the pyramidal cortical neurons of the V-VI layers and form cortical minicolumns, affects formation of cortical cytoarchitecture, neuronal plasticity and behavior in postnatal ontogenesis which testify to cortical dysfunction. Hypoxia on E18 does not significantly affect cortical structure and parietal cortex-dependent behavioral tasks.

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Structure of the parietal cortex on P5 and P20 in control rats and rats subjected to prenatal hypoxia on E14 or E18. (A) Double labeling of cortical tissue in a control rat on P5 with EdU labeling performed on E14. EdU-positive cell nuclei were stained by AlexaFluor488, Fox3-positive neurons stained by PE-conjugated secondary antibodies. Scale bar 50 μm. (B) Position of the analyzed areas in the parietal cortex (Bregma +0.20 mm; Paxinos and Watson, 2006). (C) Double labeling of cortical tissue in a control rat on P20 with EdU labeling performed on E14. EdU-positive cell nuclei were stained by AlexaFluor488, Fox3-positive neurons stained by PE-conjugated secondary antibodies. Scale bar 50 μm. (D) A coronal section of the cortical tissue of a control rat on P5, Nissl staining. Scale bar 200 μm. (E) A coronal section of the cortical tissue of a control rat on P5. EdU labeling (indicated by an arrow) on E14. The majority of the cells labeled on E14 are placed in the lower (V-VI) cortical layers. (F) A coronal section of the cortical tissue of a rat, exposed to hypoxia on E14, on P5. EdU labeling was performed on E14. (G) A coronal section of the cortical tissue of a control rat on P5 with EdU labeling performed on E18. The majority of the cells labeled on E18 are placed in the superficial cortical layers II-III. (H) A coronal section of the cortical tissue of a rat, exposed to hypoxia on E18, on P5. EdU labeling was performed on E18. (I) A coronal section of the cortical tissue of a control rat on P20, Nissl staining. Scale bar 200 μm. (J) A coronal section of the cortical tissue of a control rat on P20. EdU labeling performed on E14.
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Figure 2: Structure of the parietal cortex on P5 and P20 in control rats and rats subjected to prenatal hypoxia on E14 or E18. (A) Double labeling of cortical tissue in a control rat on P5 with EdU labeling performed on E14. EdU-positive cell nuclei were stained by AlexaFluor488, Fox3-positive neurons stained by PE-conjugated secondary antibodies. Scale bar 50 μm. (B) Position of the analyzed areas in the parietal cortex (Bregma +0.20 mm; Paxinos and Watson, 2006). (C) Double labeling of cortical tissue in a control rat on P20 with EdU labeling performed on E14. EdU-positive cell nuclei were stained by AlexaFluor488, Fox3-positive neurons stained by PE-conjugated secondary antibodies. Scale bar 50 μm. (D) A coronal section of the cortical tissue of a control rat on P5, Nissl staining. Scale bar 200 μm. (E) A coronal section of the cortical tissue of a control rat on P5. EdU labeling (indicated by an arrow) on E14. The majority of the cells labeled on E14 are placed in the lower (V-VI) cortical layers. (F) A coronal section of the cortical tissue of a rat, exposed to hypoxia on E14, on P5. EdU labeling was performed on E14. (G) A coronal section of the cortical tissue of a control rat on P5 with EdU labeling performed on E18. The majority of the cells labeled on E18 are placed in the superficial cortical layers II-III. (H) A coronal section of the cortical tissue of a rat, exposed to hypoxia on E18, on P5. EdU labeling was performed on E18. (I) A coronal section of the cortical tissue of a control rat on P20, Nissl staining. Scale bar 200 μm. (J) A coronal section of the cortical tissue of a control rat on P20. EdU labeling performed on E14.

Mentions: Double-labeling cells on P5 with EdU and a neuron-specific marker Fox3 (EdU+Fox3) showed that the majority of the cells generated on E14 or E18 in control, as well as in hypoxia-exposed animals, were neurons (Figures 2A,C). A majority of the cells EdU-labeled on E14 were localized in the lower cortical layers V-VI (Figure 2E, Table 1) while the cells labeled on E18 were mainly found in the superficial cortical layers II-III (Figure 2G and Table 1). In the course of rat development (P10-P20) the number of labeled cells decreased to 54.0 ± 8.7% compared to P5 (Figures 2D,I,J and Table 1).


Prenatal Hypoxia in Different Periods of Embryogenesis Differentially Affects Cell Migration, Neuronal Plasticity, and Rat Behavior in Postnatal Ontogenesis.

Vasilev DS, Dubrovskaya NM, Tumanova NL, Zhuravin IA - Front Neurosci (2016)

Structure of the parietal cortex on P5 and P20 in control rats and rats subjected to prenatal hypoxia on E14 or E18. (A) Double labeling of cortical tissue in a control rat on P5 with EdU labeling performed on E14. EdU-positive cell nuclei were stained by AlexaFluor488, Fox3-positive neurons stained by PE-conjugated secondary antibodies. Scale bar 50 μm. (B) Position of the analyzed areas in the parietal cortex (Bregma +0.20 mm; Paxinos and Watson, 2006). (C) Double labeling of cortical tissue in a control rat on P20 with EdU labeling performed on E14. EdU-positive cell nuclei were stained by AlexaFluor488, Fox3-positive neurons stained by PE-conjugated secondary antibodies. Scale bar 50 μm. (D) A coronal section of the cortical tissue of a control rat on P5, Nissl staining. Scale bar 200 μm. (E) A coronal section of the cortical tissue of a control rat on P5. EdU labeling (indicated by an arrow) on E14. The majority of the cells labeled on E14 are placed in the lower (V-VI) cortical layers. (F) A coronal section of the cortical tissue of a rat, exposed to hypoxia on E14, on P5. EdU labeling was performed on E14. (G) A coronal section of the cortical tissue of a control rat on P5 with EdU labeling performed on E18. The majority of the cells labeled on E18 are placed in the superficial cortical layers II-III. (H) A coronal section of the cortical tissue of a rat, exposed to hypoxia on E18, on P5. EdU labeling was performed on E18. (I) A coronal section of the cortical tissue of a control rat on P20, Nissl staining. Scale bar 200 μm. (J) A coronal section of the cortical tissue of a control rat on P20. EdU labeling performed on E14.
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Figure 2: Structure of the parietal cortex on P5 and P20 in control rats and rats subjected to prenatal hypoxia on E14 or E18. (A) Double labeling of cortical tissue in a control rat on P5 with EdU labeling performed on E14. EdU-positive cell nuclei were stained by AlexaFluor488, Fox3-positive neurons stained by PE-conjugated secondary antibodies. Scale bar 50 μm. (B) Position of the analyzed areas in the parietal cortex (Bregma +0.20 mm; Paxinos and Watson, 2006). (C) Double labeling of cortical tissue in a control rat on P20 with EdU labeling performed on E14. EdU-positive cell nuclei were stained by AlexaFluor488, Fox3-positive neurons stained by PE-conjugated secondary antibodies. Scale bar 50 μm. (D) A coronal section of the cortical tissue of a control rat on P5, Nissl staining. Scale bar 200 μm. (E) A coronal section of the cortical tissue of a control rat on P5. EdU labeling (indicated by an arrow) on E14. The majority of the cells labeled on E14 are placed in the lower (V-VI) cortical layers. (F) A coronal section of the cortical tissue of a rat, exposed to hypoxia on E14, on P5. EdU labeling was performed on E14. (G) A coronal section of the cortical tissue of a control rat on P5 with EdU labeling performed on E18. The majority of the cells labeled on E18 are placed in the superficial cortical layers II-III. (H) A coronal section of the cortical tissue of a rat, exposed to hypoxia on E18, on P5. EdU labeling was performed on E18. (I) A coronal section of the cortical tissue of a control rat on P20, Nissl staining. Scale bar 200 μm. (J) A coronal section of the cortical tissue of a control rat on P20. EdU labeling performed on E14.
Mentions: Double-labeling cells on P5 with EdU and a neuron-specific marker Fox3 (EdU+Fox3) showed that the majority of the cells generated on E14 or E18 in control, as well as in hypoxia-exposed animals, were neurons (Figures 2A,C). A majority of the cells EdU-labeled on E14 were localized in the lower cortical layers V-VI (Figure 2E, Table 1) while the cells labeled on E18 were mainly found in the superficial cortical layers II-III (Figure 2G and Table 1). In the course of rat development (P10-P20) the number of labeled cells decreased to 54.0 ± 8.7% compared to P5 (Figures 2D,I,J and Table 1).

Bottom Line: In control rat pups a majority of cells labeled on E14 were localized in the lower cortical layers V-VI while the cells labeled on E18 were mainly found in the superficial cortical layers II-III.In rat pups subjected to hypoxia on E18, the total number of labeled cells in the parietal cortex was also decreased but the number of scattered labeled neurons was higher in the lower cortical layers.Hypoxia on E18 does not significantly affect cortical structure and parietal cortex-dependent behavioral tasks.

View Article: PubMed Central - PubMed

Affiliation: I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of SciencesSaint Petersburg, Russia; Research Center, Saint-Petersburg State Pediatric Medical UniversitySaint Petersburg, Russia.

ABSTRACT
Long-term effects of prenatal hypoxia on embryonic days E14 or E18 on the number, type and localization of cortical neurons, density of labile synaptopodin-positive dendritic spines, and parietal cortex-dependent behavioral tasks were examined in the postnatal ontogenesis of rats. An injection of 5'ethynyl-2'deoxyuridine to pregnant rats was used to label neurons generated on E14 or E18 in the fetuses. In control rat pups a majority of cells labeled on E14 were localized in the lower cortical layers V-VI while the cells labeled on E18 were mainly found in the superficial cortical layers II-III. It was shown that hypoxia both on E14 and E18 results in disruption of neuroblast generation and migration but affects different cell populations. In rat pups subjected to hypoxia on E14, the total number of labeled cells in the parietal cortex was decreased while the number of labeled neurons scattered within the superficial cortical layers was increased. In rat pups subjected to hypoxia on E18, the total number of labeled cells in the parietal cortex was also decreased but the number of scattered labeled neurons was higher in the lower cortical layers. It can be suggested that prenatal hypoxia both on E14 and E18 causes a disruption in neuroblast migration but with a different outcome. Only in rats subjected to hypoxia on E14 did we observe a reduction in the total number of pyramidal cortical neurons and the density of labile synaptopodin-positive dendritic spines in the molecular cortical layer during the first month after birth which affected development of the cortical functions. As a result, rats subjected to hypoxia on E14, but not on E18, had impaired development of the whisker-placing reaction and reduced ability to learn reaching by a forepaw. The data obtained suggest that hypoxia on E14 in the period of generation of the cells, which later differentiate into the pyramidal cortical neurons of the V-VI layers and form cortical minicolumns, affects formation of cortical cytoarchitecture, neuronal plasticity and behavior in postnatal ontogenesis which testify to cortical dysfunction. Hypoxia on E18 does not significantly affect cortical structure and parietal cortex-dependent behavioral tasks.

No MeSH data available.


Related in: MedlinePlus