Perinatal brain DNA in the normal and growth hormone-treated rat

Croskerry, P. G.; Smith, Grant K.; Shepard, B.J.; Freeman, Karl B.

doi:10.1016/0006-8993(73)90683-5

Cited by 22 publications

(9 citation statements)

References 13 publications

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“…For these reasons the present results are probable pointers to the qualitative, but not the quantitative, effects of ara-C on human brain development. Ara-C exerted the much more severe effect on brain growth when given prenatally, at a time of initiation of rapid neuronal multiplication (Croskerry et aL, 1973). The deficit in brain cells at birth must have been largely of neurones, since prenatal brain cell division in this species is predominantly neuronal.…”

Section: Control !6mentioning

confidence: 96%

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A Comparison of the Effects of Cytosine Arabinoside and Adenine Arabinoside on Some Aspects of Brain Growth and Development in the Rat

Adlard

Dobbing

Sands

1975

British J Pharmacology

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Treatment of pregnant rats with cytosine arabinoside (ara-C, 50 mg/kg, i.p.) at 14 days of gestation severely impaired both prenatal and postnatal whole brain growth in their offspring, although the cerebellum was relatively less affected than whole brain. 2 Rats treated at 5 days of age with ara-C (250 mg/kg, i.p.) showed an impairment in growth of the cerebellum relative to the rest of the brain. 3 Adenine arabinoside (ara-A) treatment, either prenatally or postnatally, had negligible effect on brain growth, even at doses considerably higher than those of ara-C. 4 Adult rats, previously treated with ara-C (50 mg/kg, i.p.) at 14 days of gestation, showed an impairment in discrimination learning when tested in a water T-maze. 5 These results are discussed in relation to the proposed use of ara-C or ara-A as antiviral agents, particularly against intrauterine infection with cytomegalovirus.

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Section: Control !6mentioning

confidence: 96%

“…Such effects might be most marked if the drug were given during the major period of neurogenesis, 10 to 18 weeks of gestation in man (Dobbing & Sands, 1973) or 14 to 21 days of gestation in the rat (Croskerry, Smith, Shepard & Freeman, 1973).…”

Section: Introductionmentioning

confidence: 99%

A Comparison of the Effects of Cytosine Arabinoside and Adenine Arabinoside on Some Aspects of Brain Growth and Development in the Rat

Adlard

Dobbing

Sands

1975

British J Pharmacology

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“…For example, in man neuron formation is largely complete by 20 weeks of gestation (a), whereas rat brain neurogenesis, as assessed by accumulation of DNA, occurs between approximately 13 and 20 days of gestation (5).…”

Section: Hebb-williams Mazementioning

confidence: 99%

Maze Learning by Adult Rats after Inhibition of Neuronal Multiplication in Utero

Adlard

Dobbing

1975

Pediatr Res

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ExtractRats whose mothers received hydroxyurea (HU, 1 or 2 g/kg) at 14 days of gestation had a 30% deficit in both brain and body weight at birth, when compared with controls. Number of brain cells at birth (mainly neurons) was reduced by 33-34%. A severe reduction in postnatal whole brain growth (31-33% in adulthood) was observed, but the cerebellum was relatively spared. In the Hebb-Williams maze text in adulthood HU animals made 28% more errors than controls over 12 problems. The differences were much more marked on certain problems and for HU animals with particularly small brains. In a T-maze spatial discrimination test in adulthood HU rats either saline (10 ml/kg body weight) of HU (26) (1 or 2 g/kg body weight) suspended in a corresponding volume of saline. On the day of birth (21 or 22 days of gestational age), litters were reduced to eight animals (four males, four females) and fostered to a saline-treated mother giving birth on the same day. Both control (saline-treated) and HU animals were so fostered. A number of excess animals from each litter was killed for estimation of brain DNA (25). At 25 days of age half of the animals in each litter were killed and the whole brain and cerebellum was dissected out and weighed. The remaining animals (up to two males, two females) were weaned and subsequently housed two per cage. learned the initial response normally but, when required to HEBB-WILLIAMS MAZEreverse this response, showed a significant tendency to make more perseverative errors than controls.Rats aged 13-15 weeks were tested in a Hebb-Williams . maze (20). The light cycle was 12 hr of red, beginning at 07.00 Speculation hr, and 12 hr of white. Animals were kept at about 80% of Rats exposed to an inhibitor of cell division at the beginning of the major period of brain neurogenesis showed deficits in learning ability in adulthood. The large number of mentally retarded human children whose handicap is without known etiology may have suffered a similar early loss of neurons, and if so, this preparation could provide a useful animal model.The period of neuronal multiplication in the mammalian central nervous system is relatively short and, except in the cerebellum and hippocampus (2), occurs well before the major phase of brain growth and physiologic development. For example, in man neuron formation is largely complete by 20 weeks of gestation (a), whereas rat brain neurogenesis, as assessed by accumulation of DNA, occurs between approximately 13 and 20 days of gestation (5).It has been suggested (6) that in man certain forms of mental retardation, involving microcephaly, but the etiology thkir predicted free-feeding weight throughout the period of testing, and were run for a food reward, in two sessions/day, during the red phase of their light cycle. T-MAZERats aged 20--23 weeks were tested in a water T-maze as described previously for guinea pigs (1). The light cycle was 12 hr of red, beginning at 12.00 hr, and 12 hr of white. Rats were required to swim and make a left-right discrimination in order to...

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“…The effects of GH administration during gestation on fetal development and postnatal maturation are not as clear, and published studies report conflicting results. While some reports indicate that GH administration to pregnant rats enhances neonatal brain devel opment, resulting in precocious behavioral development and increased learning capabili ty [18][19][20][21][22][23], other studies have indicated that GH supplementation has no effect on fetal weight, placental weight [24], or perinatal brain DNA content [25,26].…”

Section: Introductionmentioning

confidence: 99%

Effects of Porcine Growth Hormone on Pregnancy and Fetal/Neonatal Development in the Rat

Spence

Mattson²,

Vetter³

et al. 1995

Neonatology

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Porcine growth hormone was given subcutaneously twice daily to two groups of 20 females at dose levels of 0.5 and 2.5 IU/kg (1 and 5 IU/kg/day). A control group of 20 females was similarly treated with vehicle. The females were given either vehicle or porcine growth hormone from gestation day (GD) 6 through GD 21, for 10 females that were cesarean sectioned, or through lactation day (LD) 21, for 10 females scheduled for natural delivery. There were no deaths, abortions, or drug-related physical signs in any treatment group. Drug-related effects during gestation were limited to significant (p < 0.05) pharmacologically mediated increases in Fo maternal body weight gain during GD 6-20 in the 2.5-IU/kg group, approximately 24% above controls. During LD 0-21, there were significant (p < 0.05) dose-related increases in average maternal body weight gain in the 0.5- and 2.5-IU/kg groups (72 and 200% above controls, respectively). Consistent with these findings, there were dose-dependent increases in maternal serum growth hormone and IGF-1 levels noted on GD 21 and LD 21 in both drug-treated groups. There were no drug-related effects on embryonal/fetal survival, GD 21 fetal body weight, placental weight, fetal femur length and width, or fetal morphology as determined by external, visceral, and skeletal examinations. There were no drug-related effects on Fi pup mortality, physical signs, body weight, biparietal diameter, liver weight, and femur length or width. These data suggest that subcutaneous administration of growth hormone to pregnant and lactating rats, at a dose that produces significant (p < 0.05) increases in maternal body weight gain and serum IGF-1 levels, has no apparent effect on embryonal/fetal development or preweaning growth.

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Perinatal brain DNA in the normal and growth hormone-treated rat

Cited by 22 publications

References 13 publications

A Comparison of the Effects of Cytosine Arabinoside and Adenine Arabinoside on Some Aspects of Brain Growth and Development in the Rat

A Comparison of the Effects of Cytosine Arabinoside and Adenine Arabinoside on Some Aspects of Brain Growth and Development in the Rat

Maze Learning by Adult Rats after Inhibition of Neuronal Multiplication in Utero

Effects of Porcine Growth Hormone on Pregnancy and Fetal/Neonatal Development in the Rat

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