Restitution of Bromodeoxyuridine‐induced Changes in Cerebellar Development

Yu, Wan-hua Amy

doi:10.1111/j.1365-2990.1979.tb00612.x

Cited by 13 publications

(15 citation statements)

References 28 publications

(19 reference statements)

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“…The times of neurogenesis of these cerebellar cell classes were not affected, compared with those reported by earlier [ 3 H]thymidine studies (Altman and Bayer, 1997). This study confirms and extends previous investigations that showed deleterious effects of BrdU on prenatal (Bannigan, 1985;Kolb et al, 1999) and postnatal (Yu, 1976(Yu, , 1977(Yu, , 1979) development and used a diverse range of BrdU concentrations and paradigms of administration.…”

Section: Discussionsupporting

confidence: 92%

“…The progressively delayed cumulative labeling over 48 hours marks the vast majority of cells in S-phase, thus allowing to birth date distinct cell populations, but the long 2 days presence of BrdU may prevent recovery from drug-inflicted damage (Wilt and Anderson, 1972;Yu, 1979) in cell populations born during a narrow time window, such as PCs or cerebellar nuclei neurons.…”

Section: Methodologic Considerationsmentioning

confidence: 98%

“…As the number of PCs regulates proliferation of granule cell precursors in the EGL (Gao et al, 1991;Smeyne et al, 1995;Goldowitz and Hamre, 1998;Wallace, 1999), the number of granule neurons may have been affected indirectly, thus amplifying reduction of the folial size. A direct effect of BrdU on the EGL, which in the rat starts to cover the cerebellar anlagen at E17 (Altman and Bayer, 1997), is probable, although, defects caused by BrdU injection prenatally can be compensated by increased mitotic activity during postnatal cerebellar morphogenesis (Yu, 1979). Indirect BrdU effects are possible on neurons of the Golgi/Lugaro and basket/stellate families and Bergmann glia, as they are numerically related to PCs and granule cells (Altman and Bayer, 1997).…”

Section: Brdu-induced Effects On Cerebellar Cell Populationsmentioning

confidence: 98%

“…BrdU may also cause teratologic effects on brain and impaired behavior, depending on the dosage and age of the recipient (Webster et al, 1973;Yu, 1976Yu, , 1977Yu, , 1979Bannigan and Langman, 1979;Nagao et al, 1997;Kolb et al, 1999).…”

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confidence: 98%

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Bromodeoxyuridine administered during neurogenesis of the projection neurons causes cerebellar defects in rat

Sekerková

Ilijić

Mugnaini

2004

J of Comparative Neurology

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Bromodeoxyuridine (BrdU) is broadly used in neuroscience to study embryonic development and adult neurogenesis. The potential toxicity of this halogenated pyrimidine analogue is frequently neglected. In this study, we administered BrdU in small doses by the progressively delayed cumulative labeling method to immunocytochemically tag different cerebellar cell types with antibodies to specific markers and BrdU in the same section. The well-known structure of the cerebellum made it possible to ascertain several toxic effects of the treatment. Time-pregnant rats were given five or six injections of 5 or 6 mg of BrdU ( approximately 12-20 mg/kg) at 8-hour intervals over 2 successive days between day 11 and 21 of pregnancy (E11-E12 to E20-E21), and the adult progeny was processed by immunocytochemistry. We demonstrate that this treatment effectively labeled distinct cerebellar cell populations but produced striking defects in the proliferation, migration, and settling of the Purkinje cells; reduced the size of the cerebellar cortex and nuclei; produced defects in the patterning of foliation; and also affected litter size, body weight, and mortality of the offspring. The observed toxic effects were consistent within individual treatment groups but varied between different treatment groups. Treatment with BrdU at the peak of neurogenesis of cerebellar projection neurons (E14) produced the most severe malformations. We observed no overt effects on the timing of neurogenesis for cerebellar neurons and glia across experimental groups. In conclusion, BrdU is a useful tool to study neural development, but its cytotoxicity represents a serious pitfall particularly when multiple doses are used to label cells.

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Section: Discussionsupporting

confidence: 92%

Section: Methodologic Considerationsmentioning

confidence: 98%

Section: Brdu-induced Effects On Cerebellar Cell Populationsmentioning

confidence: 98%

mentioning

confidence: 98%

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Bromodeoxyuridine administered during neurogenesis of the projection neurons causes cerebellar defects in rat

Sekerková

Ilijić

Mugnaini

2004

J of Comparative Neurology

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“…This situation is in contrast to other instances in which granule cells are eliminated from the EGL by X-irradiation or chemical insult to the postnatal cerebellum. In these experimental conditions, there is an amazing capacity for the regeneration of the granule cell population (Shimada and Langman, 1970a,b;Altman, 1973;Jones and Gardner, 1976;Yu, 1979;Lovell et al, 1980;Hillman, 1986, 1988;Altman and Bayer, 1997;Doughty et al, 1998). However, the extent of this regeneration is dependent on when the insult occurs and the degree of damage to the EGL.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Cerebellar Development inmath1Null Embryos and Chimeras

Jensen¹,

Smeyne²,

Goldowitz³

2004

J. Neurosci.

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The cerebellar granule cell is the most numerous neuron in the nervous system and likely the source of the most common childhood brain tumor, medulloblastoma. The earliest known gene to be expressed in the development of these cells is math1. In the math1 null mouse, neuroblasts never populate the external germinal layer (EGL) that gives rise to granule cells. In this study, we examined the embryonic development of the math1 null cerebellum and analyzed experimental mouse chimeras made from math1 null embryos. We find that the anterior rhombic lip gives rise to more than one cell type, indicating that the rhombic lip does not consist of a homogeneous population of cells. Furthermore, we demonstrate that math1 null granule cells are absent in the math1 null chimeric cerebellum, from the onset of their genesis in the mouse anterior rhombic lip. This finding indicates a vital cell intrinsic role for Math1 in the granule cell lineage. In addition, we show that wild-type cells are unable to compensate for the loss of mutant cells. Finally, the colonization of the EGL by wild-type cells and the presence of acellular gaps provides evidence that EGL neuroblasts undergo active migration and likely have a predetermined spatial address in the rhombic lip.

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Effects of 60 Hz electric and magnetic fields on the development of the rat cerebellum

Gona¹,

Yu²,

Gona³

et al. 1993

Bioelectromagnetics

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The effects of extremely low frequency (ELF) electromagnetic (EM) fields on the maturation of the rat cerebellum were studied. Newborn rats were exposed to 60 Hz electric and magnetic fields under three different combinations in a specially constructed apparatus. The pups were irradiated for 7-8 h daily, with a 30-min interruption for nursing. Pups were kept with their mothers for the remainder of the time. After approximately 1, 2, or 3 weeks of exposure, the pups were killed. Control pups were sham exposed. The somatic growth of the irradiated rats did not show any significant difference from sham-exposed controls. At 1 kV/m and 10 gauss exposure, there was a small but statistically significant decrease in cerebellar mass. In rats exposed at 1 kV/m and 10 gauss, DNA and RNA levels were significantly higher than those in sham-exposed controls at 6 and 13 days of age, but at 20 days, these two biochemical constituents were similar in both groups of rats. The ELF-EM treatment had no effect on protein and cerebroside concentrations. In terms of age effects, DNA and RNA exhibited increases from 6 to 13 days of age, and declined from 13 to 20 days. Protein and cerebroside levels exhibited increases during the 6-20-day periods. In rats exposed at 100 kV/m and 1 gauss, the DNA levels were initially less than those of sham-exposed controls at 8 days of age, reached approximately the same levels at 14 days, and then were higher than those of controls at 22 days. There was, therefore, a significant ELF-EM effect as well as a significant interaction between age and ELF-EM exposure. In terms of age effects, DNA levels for both control and exposed animals increased from 8 to 14 days. From 14 to 22 days, DNA levels of exposed rats continued to increase while those of the controls decreased. This age effect was significant. RNA levels in both groups of animals showed increases from 8 to 14 days of age, but the increase was less for the irradiated animals than for the controls. From days 14 to 22, RNA levels for both groups showed a reduction, but the decrease was greater in the irradiated than in control rats. ELF-EM treatment significantly reduced protein levels at 8 days of age, but at 14 to 22 days, protein levels of exposed rats were higher than those of controls.(ABSTRACT TRUNCATED AT 400 WORDS)

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Restitution of Bromodeoxyuridine‐induced Changes in Cerebellar Development

Cited by 13 publications

References 28 publications

Bromodeoxyuridine administered during neurogenesis of the projection neurons causes cerebellar defects in rat

Bromodeoxyuridine administered during neurogenesis of the projection neurons causes cerebellar defects in rat

Analysis of Cerebellar Development inmath1Null Embryos and Chimeras

Effects of 60 Hz electric and magnetic fields on the development of the rat cerebellum

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