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Biomedical subjects

T Matsutani

Publications and source records attributed to T Matsutani.

At least 55 records · Page 3Linked to original sources

Brain changes in rats induced by prenatal injection of methylazoxymethanol.

Various doses (0, 1, 5, 10, 15, 20, or 25 mg/kg) of methylazoxymethanol acetate (MAM), a potent alkylating agent, were injected singly into pregnant rats intraperitoneally on day 15 of gestation. Relationships between brain weights and neurochemical changes in the cerebral hemispheres (CHs; cerebral cortex and subjacent white matter, hippocampus, amygdala) and remainder of the brain (BGDM; basal ganglia, diencephalon, and mesencephalon) were examined at 60 days of age in offspring; varying degrees of microencephaly were observed. Dose-dependent reductions in the weights of CH and BGDM were observed. Reductions in total DNA content positively correlated with decreases in brain weights also observed. Dose-dependent elevations of noradrenaline (NA) and dopamine (DA) were observed in CH at MAM levels 10 mg/kg and above; dose-dependent elevations of 5-hydroxytryptamine (5-HT) were observed at 15 mg/kg and above; and in BGDM at 20 mg/kg and above dose-dependent elevations for NA and 5-HT were observed; dose-dependent elevations at 15 mg/kg and above were observed for DA. Monoamine concentrations were negatively correlated with brain weights or total DNA contents. NA and DA concentrations increased to the extent of approximately 1.3 times of control at a time when an 18% loss of CH weight was noted in animals treated with 10 mg/kg MAM. It is suggested that the above variables might be appropriately sensitive neurochemical markers for detecting minor developmental anomalies in the brain.

Alkylating Agents↗

Neurochemical effects of prenatal treatment with ochratoxin A on fetal and adult mouse brain.

Ochratoxin A (OA) is a mycotoxin produced by several storage fungi, such as Aspergillus ochraceus and several Penicillium species. OA (3 mg/kg) was given intraperitoneally to pregnant mice on day 11 of gestation (day 1 = day of insemination), and neurochemical changes in brains of their offspring were examined at fetal and adult stages. OA treatment produced retardation of intrauterine growth as well as microencephaly and reductions in total weight and DNA content of fetal brains. Specific activities of lysosomal enzymes in fetal brains began to increase by the 2nd day after treatment and to reach peak activities by the 3rd or 4th day after injection, indicative of cell death in the developing brains. Examination of brain regions of offspring three months after birth revealed that both tissue weight and DNA content were reduced to 80% of control in cerebral hemispheres (CHs; cerebral cortex and subjacent white matter, hippocampus, and amygdala) and to 90% of control in remainder of the brain (BGDM; basal ganglia, diencephalon, and mesencephalon). Total content of noradrenaline (NA), dopamine (DA) 5-hydroxytryptamine (5-HT) in treated CH showed about 15% reduction, although, expressed on a tissue weight basis, concentrations of these monoamines were increased by about 15%. Total DA content in BGDM was also reduced to 85% of controls, but total content of NA and 5-HT in BGDM and pons-medulla oblongata did not change. These results suggest that synaptogenesis of monoamine neurons in the cerebrum is impaired by prenatal treatment with OA, and that dopaminergic neurons show a slight selective vulnerability to the toxin.

Animals↗

In vitro effects of serotonin and prostaglandins on release of eggs from the ovary of the scallop, Patinopecten yessoensis.

When ovarian pieces of the scallop, Patinopecten yessoensis, were incubated in media containing serotonin (5-HT), the number of released eggs increased significantly. These eggs developed normally after fertilization. The threshold of the 5-HT effect reached a maximum at a concentration of 10(-6) M, and decreased sharply with increasing concentrations. Methysergide, a 5-HT antagonist, completely inhibited the 5-HT-induced egg release. Addition of aspirin or indomethacin to the incubation media also inhibited the 5-HT effect. However, neither aspirin nor indomethacin inhibited the 5-HT-induced egg release when 10(-6) M prostaglandin E2 (PGE2) was also present. PGE2 did not induce egg release, but enhanced the 5-HT effect. In contrast to PGE2, PGF2 alpha significantly inhibited the 5-HT effect. These results show that 5-HT induces spawning of female P. yessoensis via specific 5-HT receptors in the ovary, and that the effect of 5-HT may be regulated by PGE2 (progressive) and PGF2 alpha (suppressive).

Animals↗

[A neurochemical study of rat brain maldevelopment induced by MAM treatment at different stages of gestation].

The regional levels of several cell marker proteins in the brain and the ability of operant discrimination learning on a multiple fixed ratio (FR), fixed interval (FI) schedule were determined in rats with microencephaly induced by prenatal treatment with methylazoxymethanol (MAM), an antimitotic agent, on the 11 th to 13 th days (Group A) or on the 15 th day (Group B) of gestation. The cell marker proteins were determined with a sensitive enzyme immunoassay. Neuron-specific enolase (NSE; gamma gamma-enolase) had a significantly lowered level in the neocortex anterior in Group A. Non-neuronal enolase (NNE; alpha alpha-enolase) was significantly reduced in the superior colliculus, lateral geniculate body and optic nerve, but increased 1.5 fold in the retina in Group A. S-100b protein, a marker of astroglial cells, showed no significant change. As for the learning performance, the Group B animals showed an elevated behavioral activity and made evident discrimination between the FI and FR schedule. But Group A animals had prolonged FR components requiring responses to light on, and their spontaneous activity counts recorded by Automex showed an inhibition of behavior in light environments. These findings suggest a causative role of some developmental abnormality in the central visual system, indicated by the aberrant cell marker levels, in the disturbed learning ability of the Group A animals.

Abnormalities, Drug-Induced↗

Changes in the levels of neural cell specific proteins in the developing rat brain.

The levels of S-100 protein (S-100) and neuron-specific enolase (NSE) in the developing rat brain were determined by a sensitive enzyme immunoassay and the results were compared with those obtained by other methods. Changes with development in the levels of S-100, NSE, and 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), biochemical markers for astroglia, neurons and oligodendroglia respectively, were determined in various brain regions including the cerebral hemisphere (CH), brain stem (BS) and cerebellum (Ce). The peak increments of S-100, NSE, and CNPase activity were reached later than that of the brain weight in all of the regions. The ratios of S-100/NSE and CNPase/NSE rose during the 21 days after birth in the CH and BS; the S-100/NSE ratio in the CH began to decrease from the 21st day, whereas the CNPase/NSE ratio continued to rise even after the 30th day, suggesting different maturation periods of the different glial cells. In the Ce, the change of these ratios showed a pattern different from those in the other regions. In the CH of rats with experimental microencephaly induced by methylazoxymethanol (MAM), the ratios were almost normal, in spite of the reduction of the brain weight to about 50% of the control.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗

A neurochemical study of experimental microencephalic rat.

Methylazoxymethanol (MAM) injection to pregnant rats on day 15 of gestation caused a significant rise in monoamine concentrations accompanying a decrease in the brain weight and DNA content in the cerebral hemispheres of the offspring at 3 months of age; in the brain stem, these changes were much smaller. Similar change of monoamine concentrations was observed in cytosine arabinoside (ara-C)-induced microencephaly. The decrease of DNA content and elevation of monoamine levels were lower with MAM-injection on day 15, 13 or 17 of gestation (in that order). Serotonin content of the MAM-treated cerebral hemispheres was already 50% higher than the control immediately after birth. The activity of tryptophan hydroxylase in the MAM-treated cerebrum was 1.6 times the control value, with no change in the brain stem, while the concentration of tryptophan in the brain and plasma was equal to the control value. That the remaining neurons, axons, and oligodendroglia were intact was suggested by the normal activity of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) [EC 3.1.4.37] and levels of brain specific proteins. When neonatal rats were injected with ara-C, a decrease of DNA content per cerebellum and an elevation of monoamine concentrations in the cerebellum were found. The neonatal administration of ara-C caused an elevation of CNPase activity and myelin protein content in the cerebellum, suggesting a relative increase in myelin concentration as a result of hypoplasia of granule cells.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗

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

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.

Animals↗