Dexamethasoneが神経細胞突起の分岐・伸展に及ぼす影響

EFFECTS OF DEXAMETHASONE ON CORTICAL DENDRITIC GROWTH IN MICE

I．はじめに

　新生児・乳幼児期は，生後の脳の発育にとつて最も重要な時期であり，この時期に神経細胞の突起の分岐・伸展^28,30），髄鞘化^10）などが急激にすすみ，脳重量も急速に増加する^13）。それゆえ，このような新生児・乳幼児期の脳が薬剤，感染，レ線照射など，種々の環境因子によつて重篤な影響をうけやすいのも当然であろう。

　乳幼児期の甲状腺機能低下症など種々の内分泌疾患において，脳の発達が抑制されることは周知の事実である。最近ではさらに，このような内分泌疾患だけでなく，ステロイドホルモン剤の投与が，脳の発達に及ぼす影響についても注目されてきた。ステロイドホルモン剤は，新生児，乳幼児期においてもしばしば投与され，その副作用が危惧されるようになつた。脳に及ぼすそれの影響についても，最近，動物実験にもとづき多くの知見が得られつつある^{9,11,17,19,24,25,31,34,37）}。しかし，これらの実験研究も，そのほとんどが生化学的観点より行なわれたものである。そのため，その成績は脳の神経細胞だけでなく，支持組織をも含んだデータであり，脳のいかなる部位の，どの細胞が，どのように影響をうけるかについては，組織学的に追究しなければならない問題である。

This study was undertaken to investigate the effects of dexamethasone on brain development, with special reference to the cortical dendritic growth with Golgi-Cox method.

The mice of ICR-JCL strain were divided into the control group and the dexamethasone treated group. The latter was subdivided into three groups. The mice in group A were treated with sub-cutaneous injections of dexamethasone 3 mg/kg at 2, 3 and 4 days of age successively. The mice in group B were treated with dexamethasone 5 mg/kg at 5, 6 and 7 days of age, and the mice in group C with 5 mg/kg at 10, 11 and 12 days of age.

The mice treated with dexamethasone were much suppressed in body weight gain and in increase of body and tail length.

The brain weight of the treated mice was also significantly less than that of the control. At 20 days of age, the brains of the experimental animals were 376±17 mg (mean±SD), 362±14 mg, 398±11 mg and 427 ± 18 mg in weight in subgroup A, B, C and the control respectively. The mice in subgroup A and B were significantly less in brain weight than the mice in subgroup C. At 60 days of age, the brains were 443±23 mg and 429±21 mg in weight in subgroup A and B respectively, whereasthey were 492±19 mg in the control. The catch-up growth of the brains in the treated animals was incomplete.

At 20 and 60 days of age, the dendritic spread of the cortical pyramidal neurons in layers IV-V was examined with Golgi-Cox staining in both the treated and the control mice. The dexa-methasone treated mice showed significantly less number of intersections of dendrites with concentric circles drawn at radii of 30 μm, and 60 μm and 80 μm from the center of the perikaryon than the control. Moreover, the mice in subgroup A and Bwere significantly less in number of intersections at radii of 60 μm and 80 μm than the mice in group C and the number of dendrites arising from the perikaryal surface was also significantly less in subgroup A and B than in the control and subgroup C.

In this study the dexamethasone treatment on suckling mouse was proved to inhibit not only the body growth but also the brain development. These facts should be kept in mind in using steroid during infancy, particularly in neonatal period.