The immune state of bulbectomized mice.

Abstract

In this work, we studied the cell immunity system of mice after the surgical removal of the olfactory bulb at early and late stages of the postoperative period. We have shown earlier that, in rodents, this operation caused marked deterioration of spatial memory, an increase in the content of amyloid β , and the development of neurodegenerative process in local brain structures (including the acetylcholine-synthesizing nuclei of the forebrain) and depression-like state blocked by antidepressants [2‐4]. Interestingly, the manifestations of depression-like state in bulbectomized animals markedly decreased after the treatment with the compounds produced by immune cells (e.g., interleukin-2) [5]. It was found that, in patients with depression, a positive result of the treatment with amitryptyline was a sharp decrease in the level of tumor necrosis factor α (TNF- α ) [6]. In patients with Alzheimer’s disease, the degree of neuronal death reciprocally depended on the TNF- α level, as assessed by the intrathecal concentration of tau protein [7]. It is noteworthy that amyloid β , a key pathogenetic factor of Alzheimer’s disease, also stimulates the regeneration of TNF- α in microglia and monocytes [8]. This study was performed 1.5 and 13 months after bulbectomy, when the traits of the development of pathological process in animals were expressed most distinctly. We determined the proliferative response of T- and B-lymphocytes in the spleen; the production of tumor necrosis factor, interleukin-2 (IL-2), interleukin-3 (IL-3), and nitric oxide (NO) in peritoneal macrophages and splenic T-lymphocytes; and the concentration of TNF in blood plasma in sham-operated and bulbectomized mice 1.5 and 13 months after operation. We think that the determination of early and late changes in the cellimmunity system in bulbectomized animals is reasonable for the estimation of correlative interactions between the central nervous system (CNS) and immune system. The study was performed with eight- to ten-weekold male NMRI mice. Stereotaxic operation was performed in mice that were narcotized with Nembutal and locally anesthetized by aspiration of the olfactory bulbs through a trephine opening. Sham-operated mice were subjected to the same procedures, except for the excision of the olfactory bulbs. Blood specimens were collected from the ophthalmic vein in mice narcotized with ether. Macrophages and T- and B-lymphocytes were isolated, the proliferation of T and B lymphocytes was determined by the incorporation of 3 H-thymidine, and the production of TNF- α was measured as described in [9]. The concentration of interleukins in the supernatant after culturing T-lymphocytes was measured by immunoassay, and the production of NO was evaluated by the concentration of nitrites as described in [10].