Participation of cholinergic muscarinic system in the neuroimmune mechanisms involved in a chronic mild stress model of depression

CREMASCHI GA; SILBERMAN DM; BARREIRO ARCOS ML; AYELLI-EDGAR V; GENARO AM

Advances in Psychology Research

Nova Science Publishers, Inc.

Lugar: New York; Año: 2005; p. 123 - 139

Depressive disorders are very common in humans and constitutes a major public health problem affecting almost 4% of world wide population. Over the past several years many studies have suggested an association between depression and immunological dysfunction. Modern concepts of immunology and the growing knowledge of psychoneuroimmunology may help in understanding the distinct immunological mechanisms in psychiatric disorders. Some evidences pointing to the activation of immunocyte-mediated autoimmune reactions has been described in depression. On the other hand, some clinical and pharmacological findings evidenced the relationship between cholinergic muscarinic stimulation and behavioral depression in humans and animals. In order to deeply understand the neurobiological mechanisms involved in depression here we analyzed the participation of the cholinergic muscarinic system in a murine chronic mild stress (CMS) model of depression both at cerebral and immunocompetent cell levels. The CMS applied in mice induced a decrease in sucrose preference and a diminished learning and retention of passive avoidance behavior. This was accompanied with an increased expression of muscarinic cholinergic receptors (MR) of the M1 subtype in the frontal brain cortex in CMS animals respect to controls. Besides CMS-derived lymphocytes showed higher levels of MR but lower cGMP response to cholinergic agonist than normal T cells. Muscarinic receptors were not detectable in normal B lymphocytes while CMS-derived B cells showed both MR expression and cGMP response. B cells from CMS animals showed an increased mitogen-induced proliferation. The B cell hyperactivity was accompanied by the late onset of serum antibodies that recognized a peptide derived from the M1 cholinergic receptor from human brain. These antibodies displayed an agonistic like activity increasing some intracellular signals coupled to MR activation. The exact pathophysiological role of these antibodies remains to be elucidated.