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Biomedical subjects

M Akaike

Publications and source records attributed to M Akaike.

96 records · Page 6Linked to original sources
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Impaired Biel and radial arm maze learning in rats with methylnitrosourea-induced microcephaly.

Jc1:SD rats were given methylnitrosourea (MNU; 5 mg/kg, IP) on day 13 of gestation. Male offspring with MNU-induced microcephaly were examined on the Biel water maze and its mirror-image maze at 6 weeks of age and on a radial eight-arm maze at 14 weeks of age. The MNU rats showed postnatal depression in body weight. Their brain weight was about 60% of the control value, and they were thus microcephalic. The MNU animals made significantly more errors on the Biel maze and its mirror-image maze than the controls. In the radial arm maze test, they required more trials to acquire the learning criterion than the controls, and the animals with the acquired learning criterion were fewer. In the retest, however, no significant difference appeared in number of trials required for reacquisition of the criterion between the MNU and control animals. The autopsy of the MNU animals revealed the thinned cerebral cortex and hypoplastic hippocampus. The present results with the MNU rats confirmed the learning impairment and suggested no effect of microcephaly on retention of the acquired memory.

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Hyperactivity and spatial maze learning impairment of adult rats with temporary neonatal hypothyroidism.

Temporary hypothyroidism was induced in neonatal rats by 0.02% propylthiouracil (PTU) administration to lactating dams during days 0-19 after delivery, and its effects on the behavior and learning of their male offspring were examined. The serum T4 (thyroxine) level was returned to normal around 1 week after the last PTU administration, but the body weight gain was still depressed. The open field and Biel water maze tests at the age of 6 weeks showed an increased number of ambulations and an increase in errors with prolonged swimming time in the PTU rats. The radial arm maze test started at 13 weeks revealed that the PTU animals required more trials until they showed the first well-performed trial. The total number of choices was also larger, with less correct choices, and treatment effects on the response distribution and pattern were significant. Thus, the rats, which had suffered from temporary hypothyroidism in the neonatal period, showed hyperactivity and irreversible impairment in maze learning. These results suggest an involvement of temporary neonatal hypothyroidism in hippocampal dysfunction.

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PubMedDate not supplied

Learning/memory impairments in rat offspring prenatally exposed to phenytoin.

Phenytoin (PHT) was orally administered in dosages of 50 and 100 mg/kg/day to pregnant rats on days 7-18 of gestation. Offspring were tested on the negative geotaxis test, a figure-eight maze (F8), the Biel water maze (BM), the Morris maze (MM), and the radial maze (RM). In addition, a delayed nonmatching-to-sample (DNMTS) test was employed. The levels of neuropeptides in brain and brain weights were determined. The maturation of negative geotaxis was delayed in both PHT groups. PHT groups showed no differences in F8, BM, and MM. In the RM, the total number of choices was high, whereas the number of correct choices was low. In the DNMTS, PHT groups showed low for correct choices with a long interval. The concentrations of neuropeptides were changed in the mesolimbic cortex, hippocampus, and amygdala. Brain weights were lower at 6 weeks of age in the 100 mg/kg/day PHT group, but were comparable at 16 weeks of age. This study suggests that the RM is a detectable task for the learning/memory impairments induced by PHT. In addition, it is surmised that the learning deficit is due to a working memory impairment arising from abnormal changes in neuropeptides and an injury in the fetal hippocampus.

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PubMedDate not supplied

Angiogenesis in hepatocellular carcinoma as evaluated by alpha smooth muscle actin immunohistochemistry.

BACKGROUND/AIMS: Angiogenesis has been known to be associated with tumor development. In this study, neovascularization in small hepatocellular carcinoma was investigated by evaluation of intratumoral arteriole counts, using alpha smooth muscle actin antibody immunohistochemistry. METHODOLOGY: Surgical specimens from 38 patients with small hepatocellular carcinoma were immunostained for alpha smooth muscle actin and proliferating cell nuclear antigen. The correlation between intratumoral arteriole density and clinicopathological factors including angiographic findings, proliferative activity, and patient prognosis were analyzed. RESULTS: Significant difference in intratumoral arteriole density were observed between well-differentiated hepatocellular carcinoma and poorly differentiated hepatocellular carcinoma (P = 0.004) or moderately differentiated hepatocellular carcinoma and poorly differentiated hepatocellular carcinoma (P = 0.011). The mean intratumoral arteriole count in the tumors showing angiographic hypervascularity was significantly higher than that in the tumors without angiographic hypervascularity (P = 0.011). A significant and positive correlation was found between proliferating cell nuclear antigen labeling index and intratumoral arteriole density (r = 0.5232, P = 0.001). A high intratumoral arteriole density in tumor was significantly correlated with shorter patients survival (P = 0.018). Cox's multivariate regression analysis showed that the intratumoral arteriole density was independent prognostic factors (P = 0.0306). CONCLUSIONS: Intratumoral arteriole density was found to be significantly associated with histological grade, proliferative activity, and patient survival. It also reflected the angiographic findings. Alpha smooth muscle actin antibody immunohistochemistry would provide a simple and biologically significant method which is usable to screen neovascularization and arterial blood supply in hepatocellular carcinoma, and may have predicting utility for patients outcome. This technique is applicable to routine paraffin sections, and may be useful as an adjunct to surgical pathology of hepatocellular carcinoma.

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