A neurochemical study of developmental impairment of the brain caused by the administration of cytosine arabinoside during the fetal or neonatal period of rats

Abstract

Injection of pregnant rats with cytosine arabinoside (ara-C) (280 mg/kg) on day 15 of gestation caused a significant rise (about two times the control value) in monoamine concentrations (norepinephrine, dopamine, and serotonin) accompanied by a decrease (about 60% of the control) in the brain weight and DNA content in the cerebrum of the offspring at 60 days of age. When neonatal rats were injected with ara-C (30 mg/kg/day) for four consecutive days from the fourth to seventh days after birth, a decrease of DNA content per cerebellum and an elevation of monoamine concentrations in the cerebellum were found. However, the total content of each monoamine per cerebrum or cerebellum showed no difference from the control. These results suggest that monoaminergic neurons may remain intact, with normal monoaminergic synapses compressed into a small brain volume. The neonatal administration of ara-C caused an elevation of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) (EC 3.1.4.37) activity and myelin protein content in the cerebellum, suggesting a relative increase in myelin concentration as a result of hypoplasia of granule cells.

Altered prepulse inhibition in rats treated prenatally with the antimitotic Ara-C: an animal model for sensorimotor gating deficits in schizophrenia

“…Adlard et al 1975;Percy 1975;Woodward et al 1975;Johnston and Coyle 1979;Matsutani et al 1983;Ohno 1984;Chen and Hillman 1986;Gray et al 1986;Ono et al 1992;Gillies and Price 1993;Freeman et al 1995;Ferguson et al 1994Ferguson et al , 1996. One important finding from these experiments is that the timing and dose of the drug injection are key factors in determining the type and extent of damage to the developing nervous system.…”

Subchronic effects of ochratoxin A on young adult rat brain and partial prevention by aspartame, a sweetener

“…23,41 Numerous studies have been made to evaluate the biochemical and neurochemical changes of microcephalic mice and rats. 23,41 In fact these authors have found a reduction (15 ± 80%) in monoamine such as dopamine, noradrenaline and serotonine contents accompanied by a decrease in the brain weight and DNA content in selected brain regions in offspring at the age of 60 days, (about 60% of the controls), 28,42 at the age of 90 days (about 80% of the controls). 28 Elevated speci®c activities of lysosomal enzymes (deoxyribonuclease, b-galactosidase, b-glucuronidase) were also observed in such studies.…”

“…28 Elevated speci®c activities of lysosomal enzymes (deoxyribonuclease, b-galactosidase, b-glucuronidase) were also observed in such studies. 28,42 The lake or decrease of monoamine neurotransmitters in some areas of brain could be detrimental to the normal brain physiology.…”

Biochemical and histological changes produced by sweeteners and cytarabine in the brain of young rats

“…Official statistics reported 80% of prevalence diagnoses patients on treatment survive to malignant tumors (7). Chemotherapy is a useful tool to attack cancer and mellow down the sufferings which it entails, and cytarabine is the most common chemotherapeutic agent used in children (8), although its use is accompanied by elevation of monoamine concentrations in the brain regions (9). Guidelines on sugar consumption by the World Health Organization (WHO) recommend non-sugar sweeteners such as stevia and splenda as healthy sugar replacement alternatives (10).…”