Search

It has been suggested that inflammatory processes may play a role in the development of Alzheimer's disease (AD), and that nonsteroidal anti-inflammatory drug treatments may provide protection against the onset of AD. In the current study male Wistar rats were trained in two-lever operant chambers under an alternating lever cyclic-ratio ratio (ALCR) schedule. When responding showed no trends, subjects were divided into groups. One group was bilaterally injected into the CA3 area of the hippocampus with 5 microl of aggregated beta-amyloid (Abeta) suspension, and one group was bilaterally injected into the CA3 area of the hippocampus with 5 microl of sterile saline. Subgroups were treated twice daily with 0.1 ml (40 mg/kg) ibuprofen administered orally. The results indicated that chronic administration of ibuprofen protected against detrimental behavioural effects following aggregated Abeta injections. Withdrawal of ibuprofen treatment from aggregated Abeta-injected subjects produced a decline in behavioural performance to the level of the non-treated aggregated Abeta-injected group. Ibuprofen treatment reduced the numbers of reactive astrocytes following aggregated Abeta injection, and withdrawal of ibuprofen resulted in an increase of reactive astrocytes. These results suggest that induced inflammatory processes may play a role in AD, and that ibuprofen treatment may protect against some of the symptoms seen in AD.

The expression of insulin-like growth factor-1 (IGF-1) was examined in subcutaneous (SQ) adipose tissue from 105-day pig fetuses by ribonuclease protection assays and in situ hybridization using a porcine IGF-1 riboprobe. Fetuses were hypophysectomized (hypox) at 70 days of gestation and at 90 days thyroxine (T4) pellets were implanted into some of the hypox fetuses. Fetuses were removed and SQ tissues collected on day 105 of gestation. RNase protection assays followed by scanning laser densitometry revealed that IGF-1 mRNA in SQ adipose tissue in hypox fetuses was significantly decreased to 19.8 +/- 1.2% of control values. T4 treatment increased the expression of IGF-1 by 174 +/- 26.6% of values for hypox fetuses. Using in situ hybridization we showed that fetal hypophysectomy reduced and T4 treatment increased expression of IGF-1 mRNA in the outer SQ adipose tissue layer (P0.05). However, T4 treatment after hypox did not influence IGF-1 expression in the inner SQ layer (P0.05). IGF-1 was expressed around capillaries, in small fat cells, and in fibroblasts in loose and dense connective tissue. Large fat cells, however, did not express IGF-1. Collectively, we concluded that (1) IGF-1 mRNA was decreased after hypox and increased by T4 treatment in SQ tissue of 105-day fetuses; (2) The expression of the IGF-1 gene was more sensitive to T4 treatment after hypox in outer SQ tissue than in inner SQ tissue; (3) Most stromal cells produced IGF-1 mRNA, and as a result they may influence adipogenesis in the outer layer of SQ adipose tissue; and (4) Once fat cells enlarged, expression of IGF-1 was not detected. Therefore, these studies provide evidence that IGF-1 may mediate the influence of T4 on fetal adipogenesis.

Histochemistry and electron microscopy were used to study the adrenergic innervation of subcutaneous adipose tissue in fetal pigs. Adrenergic innervation was present around arteries, arterioles, and adipocyte-associated capillaries. Nerve fibers were infrequently observed around veins, venules, and adipocytes. Ultrastructural features of nerves included mitochondria, clear synaptic vesicles, and a small number of vesicles with a core of electron-dense material. Innervation of adipose tissue was similar in 70-, 90-, and 110-day-old fetuses. Examination of fetuses decapitated at 45 days of gestation and removed at 110 days showed that adrenergic innervation was absent in adipose tissue of decapitated fetuses. Adrenergic innervation was also absent in adipose tissue from fetuses hypophysectomized at 72–73 days of gestation and examined at 110 days. These data indicate that fetal porcine adipose tissue may be under neural control by day 70 of gestation. Furthermore, an intact pituitary is necessary for the development of adrenergic innervation in fetal adipose tissue.

The effect of fetal decapitation on skeletal muscle growth and development in utero was studied in the pig. Pig fetuses were decapitated at 45 days of gestation and the peroneus longus muscle was analyzed at 110 days of gestation. Muscle wet weight, length, minimum fiber diameter, DNA, RNA, protein content, and incidence of muscle fiber nuclei and satellite cell nuclei were determined in the decapitated fetus and in sham-decapitated control fetuses. Decapitation did not significantly influence (p > 0.05) any of the traits measured. Muscle and satellite cell ultrastructure was not altered by decapitation. Therefore, an intact brain and hypothalamic-hypophyseal axis are not critical to growth and development of fetal pig skeletal muscle as measured in this study.