Postnatal proliferation of DRG non‐neuronal cells in vitamin E‐deficient rats

Changes in the number of satellite cells in neuron body sheaths in dorsal root ganglia (DRGs) were studied from 1 to 5 months of age in control and in vitamin E‐deficient rats; furthermore, the satellite cell proliferation rate was detected in the same groups of animals with immunohistochemistry for 5‐bromo‐2′‐deoxyuridine (BrdU). The number of satellite cells in sheaths of DRG neurons increased in the period of life considered both in control and in vitamin E‐deficient rats. Satellite cell proliferation was observed in both groups, but its rate was found to be higher in vitamin E‐deficient rats. The results obtained in control rats confirm that mitotic ability is retained by satellite cells in adulthood and show that at least some of newborn satellite cells add to the pre‐existing population. The results obtained in vitamin E‐deficient rats suggest that a faster turnover in satellite cell population takes place in these animals and support the idea that vitamin E could be an exogenous factor controlling cell proliferation. Anat Rec 256:109–115, 1999. © 1999 Wiley‐Liss, Inc.     

Effects on neural function of repleting vitamin E-deficient rats with alpha-tocopherol

A severe and chronic deficiency of vitamin E (alpha-tocopherol) is associated with a characteristic neurological syndrome with typical "clinical," neuropathological, and electrophysiological abnormalities in both humans and experimental animals. Repletion of vitamin E-deficient human subjects with alpha-tocopherol typically halts the progression of the neural signs and symptoms, and in some cases, can result in objective improvement. Electrophysiological parameters provide an objective measure of neural and visual function and improvement of some of these measures has been reported after repletion with vitamin E in humans. In this longitudinal study, the effects of repleting rats with a diet containing 36 mg/kg all-rac-alpha-tocopheryl acetate for 20 wk after they had been receiving a vitamin E-deficient diet for 38 wk was studied. We report significant improvements in growth and a number of electrophysiological parameters of both neural and visual function after repletion. These results confirm the validity of the vitamin E-deficient rat as a model of vitamin E deficiency in humans.     

Glutathione and ascorbic acid metabolism and antioxidative enzyme activity in tissues of vitamin E-deficient rats

Vinnitsa Medical Institute. All-Union Cardiologic Scientific Center, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR I. K. Shkhvatsabaya [deceased]. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 107, No. 4, pp. 437–438, April, 1989.     

Proliferation of non-neuronal cells in spinal cords of irradiated, immature rats following transection of the sciatic nerve.

Transection of a peripheral nerve not only elicits changes in the injured neurons but also results in an increase in non-neuronal cells, considered by most workers to be neuroglia, in the region of these neurons. Since studies in this laboratory have shown that the neuroglial population of spinal cords of immature rats can be reduced markedly by ionizing radiation, the present investigation was undertaken to determine if this reaction would occur in the irradiated spinal cord following transection of the sciatic nerve. In order to answer this question the sciatic nerve was sectioned unilaterally at 17 days of age (14 days post-irradiation). Sham-irradiated littermates served as controls. Light microscopic examination showed an increase in non-neuronal cells throughout the gray matter on the side of axotomy in spite of a decreased neuroglial population in the 2,000 R and 3,000 R groups. These cells were scattered in the neuropil or were adjacent to injured neuronal perikarya in the anterior horn. Qualitatively similar reactions occurred in the 500 R and 1,000 R groups and in shamirradiated controls. Whether the magnitude of response is the same in all groups is currently under investigation, as are questions dealing with the origins of the reactive cells.     

Age-related alterations in antioxidant capacity and lipid peroxidation in brain, liver, and lung homogenates of normal and vitamin E-deficient rats.

Age-related alterations in both antioxidant capacity and lipid peroxidation in the cerebrum, lung and liver homogenates of normal and vitamin E-deficient rats were investigated. The antioxidant capacity, which includes superoxide dismutase, catalase and glutathione peroxidase activities and vitamin E (alpha-tocopherol) concentration, was relatively stable throughout the lifespan. It was observed, however, that catalase and glutathione peroxidase activities in livers of old rats decreased and that vitamin E concentration in lung and liver increased with age. In vitamin E-deficient animals, catalase activity in liver increased and glutathione peroxidase activity in liver and lung decreased. Lipid peroxidation was monitored by use of three different indices, i.e. the thiobarbituric acid (TBA) value, oxygen absorption and conjugated-diene formation. In the absence of any initiator, neither oxygen absorption into tissue homogenates nor conjugated-diene formation in lipid extracts from the homogenates occurred. The TBA value of each cerebrum homogenate incubated under air or an oxygen atmosphere was larger than that of the corresponding unincubated cerebrum homogenate. From comparison between the TBA value and oxygen absorption, this increase in the TBA value was suggested to be due to some reactions other than lipid peroxidation. Although tissue homogenates examined contained TBA-reacting materials, no lipid peroxidation seems to arise during incubation of them. No age-related alterations in the TBA value and oxygen absorption in rat tissue homogenates were observed. Vitamin E deficiency had no effect on the TBA values of cerebrum and lung homogenates, while it seemed to increase the TBA values of liver homogenates. Vitamin E deficiency had no effect on oxygen absorption in these tissue homogenates. The induction period of initiator-induced conjugated-diene formation in lipid extracts from liver and lung homogenates from normal and vitamin E-deficient rats tended to be extended with age. Vitamin E deficiency decreased the induction period of initiator-induced conjugated-diene formation. As a result, the length of the induction period was found to be proportional to vitamin E concentration in lipid extracts. The overall antioxidant capacity of rat tissues appears to be maintained without large variation during ageing. Decreases in the capacity of some antioxidant factors may be compensated by increases in the capacity of other factors.     

大鼠脊髓硫酸软骨素蛋白多糖4细胞的生后发育特征

 目的 研究大鼠脊髓中硫酸软骨素蛋白多糖4（NG2）细胞生后发育特征。方法 采用免疫组织化学及Western blot,观察生后不同发育阶段的脊髓中NG2细胞形态变化。结果 免疫组织化学染色显示,在大鼠生后各发育阶段的脊髓内均有NG2细胞表达;脊髓内NG2细胞胞体逐渐增大,其形态由圆形或卵圆形变为不规则形,突起数目和长度随之增加。与同时期大脑皮层的NG2细胞形态比较,脊髓内的NG2细胞胞体要大,突起短而少。Western blot显示,P1d,脊髓内NG2表达水平最高, P7d开始下降,P21d最低,P60d回升。结论 在大鼠不同发育阶段的脊髓内,NG2细胞形态数量不同, P7d到P21d是脊髓内神经纤维髓鞘主要形成期;脊髓内NG2细胞可能处于少突胶质细胞系发育的早期阶段。     

Increase in the number of non-neuronal cells in superior cervical ganglia of developing rats after contralateral ganglionectomy

The left superior cervical ganglion of 3-day-old rats was subjected to preganglionic nerve division, ganglionectomy, or sham operation, while the right ganglion was left intact. Thirty days later, both the left and the right ganglia were perfusion-fixed and examined for weight and volume, as well as for the number and the density of the principal nerve cells and the non-neuronal cells. The small intensely fluorescent cells were counted from a separate set of freeze-dried ganglia.Unilateral preganglionic nerve division caused in the left operated side a significant loss of ganglion weight and volume due to a decreased number of non-neuronal cells, while no significant changes occurred in the right intact ganglion. Unilateral left ganglionectomy caused a significant increase in the mean ganglion weight and in the number and the density of the non-neuronal cells in the right intact ganglion, while the number and the density of the principal nerve cells and the small intensely fluorescent cells were not affected by this operation.It is suggested that normal development of the ganglionic satellite cells requires the presence of normally innervated principal cells. Furthermore, unilateral ganglionectomy induces a greater than normal proliferation of the satellite cells contralaterally, possibly by causing an increase in the activity of the contralateral ganglion.     

Postnatal development of beta-cells in rats. Proposed explanatory model

The previously shown wave of beta-cell apoptosis and the apparent plateau in the beta-cell mass in the third week of life in rats are still unexplained events. Using a novel design-based stereological method we investigated the postnatal development of the beta-cell population in Sprague-Dawley rats. The total beta-cell mass increased from postnatal day 4 until day 16, to be followed by a plateau until day 24, after which it increased further. This plateau was caused by beta-cell hypotrophia as well as decreased net beta-cell formation. The beta-cell mass per unit body weight (the relative beta-cell mass) was five times higher at birth compared with the adult constant level that was reached at approximately 24 days of age. We propose an explanatory model for the postnatal development of the beta-cell population in rats. According to this model, beta-cells in the early postnatal period are immature, i.e. are not susceptible to the mechanism that in later life maintains a constant relative beta-cell mass. Within the following weeks the number of mature beta-cells increases, and from approximately day 24 and onwards the beta-cell population is dominated by mature beta-cells that adjust to match the body weight, keeping a constant relative beta-cell mass. Findings of an apoptotic wave, a plateau phase in the total beta-cell mass development, a period with beta-cell hypotrophia, and the disappearance of insulin-like growth factor II positive beta-cells at postnatal day 21 all fit well in the model.     

Chlorphentermine-induced alterations in the lungs of vitamin E-deficient and -supplemented rats: quantitative ultrastructural analysis of Type II Cell response

Response of alveolar Type II (T-II) cells of male Sprague-Dawley weanling rats maintained on vitamin E (VE)-deficient and -supplemented diets to chlorphentermine (CP) treatment was evaluated. Ultrastructural and quantitative procedures were used to assess the T-II cell-drug interaction. Subjective examination of photomicrographs revealed numerous disrupted surfactant lamellar bodies in the CP-treated animals, as compared to fewer in controls. In addition, an unusual amorphous material was associated with these cells in drug-treated animals. Quantitative assessment confirmed the above subjective impression and revealed an increase in the size of T-II cells in treated rats. Morphometric evaluation showed that CP treatment significantly altered the volume density of cytoplasm, mitochondria, and rough endoplasmic reticulum (RER). Furthermore, a significant interaction between the diet and treatment with respect to volume fractions of mitochondria, RER, and Golgi complex was observed. The present study indicates that cytoplasmic components in T-II cells are altered as a result of CP treatment and that VE status of the animals influences the nature and extent of these alterations.     

Lack of tocopherol in peripheral nerves of vitamin E-deficient patients with peripheral neuropathy

Vitamin E deficiency is often associated with symptoms of a peripheral neuropathy. To evaluate whether vitamin E deficiency affects the vitamin E content of the peripheral nervous system, we measured the alpha-tocopherol content in biopsy specimens of sural nerve and adipose tissue from 5 patients with symptomatic vitamin E deficiency (2 with homozygous hypobetalipoproteinemia and 3 with familial isolated vitamin E deficiency) and 34 control patients with neurologic diseases without vitamin E deficiency. A significant reduction in tissue tocopherol content was present in the vitamin E-deficient patients, as compared with the controls, both in sural nerves (1.8 +/- 1.2 vs. 20 +/- 16 ng per microgram of cholesterol [P less than 0.001], or 7.7 +/- 5.4 vs. 64 +/- 44 ng per milligram of wet weight [P less than 0.01]) and in adipose tissue (46 +/- 43 vs. 222 +/- 111 ng per milligram of triglyceride [P less than 0.001]). Levels of tocopherol in adipose tissue were significantly correlated (P less than 0.001) with levels in peripheral nerves. The low tocopherol content of the nerves preceded histologic degeneration in three vitamin E-deficient patients, suggesting that the nerve injury resulted from the low nerve tocopherol content.     

Proliferation of non-neuronal cells in spinal cords of irradiated,immature rats following transection of the sciatic nerve

Transection of a peripheral nerve not only elicits changes in the injured neurons but also results in an increase in non-neuronal cells, considered by most workers to be neuroglia, in the region of these neurons. Since studies in this laboratory have shown that the neuroglial population of spinal cords of immature rats can be reduced markedly by ionizing radiation, the present investigation was undertaken to determine if this reaction would occur in the irradiated spinal cord following transection of the sciatic nerve. In order to answer this question the sciatic nerve was sectioned unilaterally at 17 days of age (14 days post-irradiation). Sham-irradiated littermates served as controls. Light microscopic examination showed an increase in non-neuronal cells throughout the gray matter on the side of axotomy in spite of a decreased neuroglial population in the 2,000 R and 3,000 R groups. These cells were scattered in the neuropil or were adjacent to injured neuronal perikarya in the anterior horn. Qualitatively similar reactions occurred in the 500 R and 1,000 R groups and in shamirradiated controls. Whether the magnitude of response is the same in all groups is currently under investigation, as are questions dealing with the origins of the reactive cells.     

Haloperidol normalized prenatal vitamin D depletion-induced reduction of hippocampal cell proliferation in adult rats

Considering the fact that schizophrenia is a highly complex disorder of the human brain, different models are needed to test specific causative or mechanistic hypotheses. The pathogenesis of schizophrenia is also characterized by abnormal neuronal development. It was found that schizophrenia as well as antipsychotic treatment are accompanied by alterations in neuronal proliferation. Recently we reported on increased neurogenesis and their controllability by neuroleptics in a pharmacological (ketamine) model of schizophrenia. To complete our understanding, here we studied neurogenesis and its sensitivity to the classical neuroleptic haloperidol in a developmental model of schizophrenia (maternal vitamin D deficiency). It was found that maternal vitamin D deficiency resulted in decreased neurogenesis. This effect was ameliorated by subchronic treatment with haloperidol. Thus, the results complete previous findings concerning the ability of haloperidol to ameliorate behavioral abnormalities induced by prenatal vitamin D deficiency and introduce the possibility to explain the curative effects of haloperidol, at least in part, due to re-establishment of disturbed cell proliferation.