Depletion of thymic macrophages in the rat by liposome-encapsulated dichloromethylene diphosphonate.

Liposome-entrapped dichloromethylene diphosphonate (Cl2MDP) was injected locally into the thymus of adult rats. This treatment, which has been found to deplete resident macrophages in other organs, also reduced the number of thymic macrophages. The depletion was evident in the cortex and the corticomedullary zone at 5, 13 and 23 days after Cl2MDP treatment, while the decrease in medullary macrophages only became significant 13 and 23 days after injection. However, the maximal reduction of macrophages was evident 13 days after this treatment. Thirty-five days after Cl2MDP treatment, macrophages repopulated the thymus. Our results suggest that the cortical and cortico-medullary macrophages have a high phagocytic activity consistent with their predominant role as scavengers of the large numbers of thymocytes that die under physiological conditions. It is concluded that liposome-mediated depletion of thymic macrophages can serve as an experimental model to study the roles of these cells.

Effects of cyclosporin A on some accessory cells of rat thymus.

We used immunohistochemistry with monoclonal antibodies (TRPM1, TRPM2) and histochemistry (acid phosphatase (AcP)) to investigate the effects of cyclosporin A (CsA) on macrophages and interdigitating cells (IDCs) in adult rat thymus after 21 days of treatment, and 21 days after stopping treatment. We also studied the development of IDCs and macrophages in 2, 6, 12, 20 and 30-day-old rats after 21 days of CsA administration to the pregnant mothers. In adult rats after 21 days of CsA treatment, IDCs were absent and only a small number of macrophages were present in the cortex; 21 days after stopping treatment the distribution of IDCs and macrophages had become similar to that in normal adults. The AcP+ macrophages in treated adult rats disappeared, as shown by immunohistochemistry, 21 days after CsA treatment and were again present, similarly to control animals, 21 days after stopping treatment. Therefore CsA causes the thymus medulla of adult rats to disappear and also a significant decrease in the macrophage population. We also found that while in normal rat neonates the thymus has the features of the adult thymus by the 12th day, in neonates from CsA treated mothers this did not appear until the 30th day. CsA treatment to pregnant rats delays thymus development in the young animals but does not cause persisting morphological alterations. This last finding was similar to that observed in adult rats 21 days after the end of CsA treatment.

A light and electron microscope study of rat abducens nucleus neurons projecting to the cerebellar flocculus.

Injection of horseradish peroxidase (HRP) into the cerebellar flocculus of the rat was employed to identify neurons in the abducens nucleus that project to the flocculus. The number, ultrastructural features and precise localisation of these neurons in the nucleus were examined. They were present bilaterally and represented about 7% of the total neuronal population of each nucleus. They were localised principally in the dorsomedial area of the cranial half of each nucleus and did not display the typical ultrastructural features of motoneurons. It is concluded that the localisation and ultrastructural characteristics of these HRP-positive neurons are useful for distinguishing them from other neuronal populations within the nucleus.

Lysosomal changes in rat spinal ganglia neurons after prolonged treatment with cisplatin.

We performed morphometric and ultrastructural studies to determine the morphological response of rat spinal ganglion sensory neurons to prolonged administration of cisplatin up to a total dose of 18 mg/kg. We quantitated the different types of lysosomal system (LS) bodies present (primary and secondary lysosomes, lipofuscin granules) as well as multivesicular bodies in treated and control animals. Five rats were examined per group. This ultrastructural study on cisplatin-induced changes in LS of spinal ganglia neurons shows that the total area and total number of LS structures are significantly increased by cisplatin treatment. The main specific changes were increase in number of small-size lysosomes and increase in number of polymeric lipofuscin granules. Other alterations observed were presence of nucleolar segregation, patches of neurofilaments and deposits of osmiophilic material in the perikaryon and axon hillock, all indicating that sensory neurons are a major target of cisplatin.

Immunohistochemical study of cyclosporin-A on rat thymus after various treatment times.

The effects of the immunosuppressive agent cyclosporin A (CsA) after 4, 8, 15, and 21 days of treatment were investigated in the thymus of 12 week-old rats by an immunochemical method using the TRPM1 and TRPM2 monoclonal antibodies. Major changes were not observed after 4, 8 and 15 days' treatment. But thymus histology completely changed after 21 days: Interdigitating (TRPM1-positive) cells completely disappeared and only a small number of (TRPM1-positive) macrophages were observed in the thymus cortex. TRPM2-positive cells also decreased, most markedly in the outer cortex and cortex. These findings indicate that inhibition of T-lymphocyte maturation is linked to disappearance of interdigitating cells which produce cytokines with proliferative and differentiation properties.

The rat abducens nucleus: a histo- and immunohistochemical study.

The number and proportion of motoneurons and interneurons present in the rat abducens nucleus was determined by the use of ChAT immunostaining and of HRP staining after retrograde transport from the injected right lateral rectus muscle. After HRP injection 67% of abducens neurons took up HRP and were hence motoneurons to the muscle. The cell bodies were mainly located in the middle third of the nucleus and were either spindle-shaped or pyriform. By ChAT-immunohistochemistry, 77% of the rat abducens neurons were ChAT-positive. After considering and discarding the hypotheses that the lateral rectus muscle could be incompletely filled by HRP, and that other muscles may be innervated by abducens motoneurons, it is concluded that some interneurons of the abducens nucleus of the rat are probably cholinergic.

Unmyelinated nerve fibers associated with Meissner's corpuscle in the green monkey (Cercopithecus aethiops L.).

The ultrastructure and organization of free nerve fibers occurring in dermal papillae containing Meissner's corpuscles were studied in the fingertips of the Green Monkey (Cercopithecus aethiops L.). The course of the thin unmyelinated fibers leads in the vicinity of Meissner's corpuscles in the connective tissue of its sheaths, between the epidermis and the peripheral fibroblast layer; they never come into contact with the nervous component of the receptor. Consequently, neither a "pericorpuscular reticulum" nor an "apparatus of Timofeew" is formed. The presence of thin axons containing dense-cored vesicles is evident, but they are not autonomous fibers, as indicated by the negative results of the Falck-Hillarp test for catecholamines. The nerve fibers occasionally seem to bear a close resemblance to the "open" and "plain" endings described by other authors in papillae devoid of corpuscles. Despite failure for close mutual contact to be established between the Meissner's corpuscle and the unmyelinated fibers ramifying in the connective tissue surrounding it, the hypothesis that the two may cooperate to form a "multimodal sensory package" is not without interest.

Electron microscopic demonstration of cerebello-oculomotor fibres in cat.

Few synaptic buttons with the typical changes of "electron-dense degeneration" were found in the nucleus of the oculomotor nerve of cats, which underwent complete bilateral ablation of the cerebellum. The degenerating buttons were mainly found in the neuropil, contacting small dendritic profiles. For the scanty number of degenerating buttons observed and for the particular location of its terminal buttons, the direct cerebello-oculomotor connection appears to be an ancillary route in the cerebello-oculomotor linkage, which involves mainly polysynaptic routes.