Patients suffering autoimmune diseases show higher incidence of mental disorders compared to patients suffering other chronic pathologies. For instance, about 40% of patients affected by multiple sclerosis have tried to commit suicide [1] while more than 30% of patients with autoimmune hepatitis also suffer from schizophrenia [2]. We have identified a new ¿emotional modulator¿ protein produced by immune cells called immuno-moodulin (Imud). In this thesis, I have investigated the nature and the role of this protein in mood disorders and in spermatogenesis [3]. Firstly, the cellular and tissues expression and the protein relation with spermatogenesis has been explored. Surprisingly, even if the concentration of protein was higher in the testicles as expected, no significant differences were observed in spermatogenesis while the protein was injected in wild type mice. In order to investigate its role in mental disorder, we cloned and produced our ¿in house¿ Immuno-moodulin. During both the protein production and the investigation of the protein expression levels, Imud tented to oligomerize. In the meanwhile, 15 anti-Imud hybridomas produced with genetic immunization technology were screened with western blot and immunoprecipitation to select and produce a monoclonal anti-Imud antibody. Two Final candidates were chosen and sent to be purified. Finally, the two purified monoclonal antibodies and the produced and purified recombinant protein were injected in C57BL/6 male mice and behavioural test were performed to investigate differences in anxiety-like behaviour. Results showed an increase in anxiety-like behaviour after the treatment with the recombinant protein, while administration of the two monoclonal antibodies against immuno-moodulin had an observed ¿relaxing¿ and ¿calming¿ effect.
Immuno-moodulin: a new target for emotional disorders
OGGERO, SILVIA
2014/2015
Abstract
Patients suffering autoimmune diseases show higher incidence of mental disorders compared to patients suffering other chronic pathologies. For instance, about 40% of patients affected by multiple sclerosis have tried to commit suicide [1] while more than 30% of patients with autoimmune hepatitis also suffer from schizophrenia [2]. We have identified a new ¿emotional modulator¿ protein produced by immune cells called immuno-moodulin (Imud). In this thesis, I have investigated the nature and the role of this protein in mood disorders and in spermatogenesis [3]. Firstly, the cellular and tissues expression and the protein relation with spermatogenesis has been explored. Surprisingly, even if the concentration of protein was higher in the testicles as expected, no significant differences were observed in spermatogenesis while the protein was injected in wild type mice. In order to investigate its role in mental disorder, we cloned and produced our ¿in house¿ Immuno-moodulin. During both the protein production and the investigation of the protein expression levels, Imud tented to oligomerize. In the meanwhile, 15 anti-Imud hybridomas produced with genetic immunization technology were screened with western blot and immunoprecipitation to select and produce a monoclonal anti-Imud antibody. Two Final candidates were chosen and sent to be purified. Finally, the two purified monoclonal antibodies and the produced and purified recombinant protein were injected in C57BL/6 male mice and behavioural test were performed to investigate differences in anxiety-like behaviour. Results showed an increase in anxiety-like behaviour after the treatment with the recombinant protein, while administration of the two monoclonal antibodies against immuno-moodulin had an observed ¿relaxing¿ and ¿calming¿ effect.I documenti in UNITESI sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
https://hdl.handle.net/20.500.14240/73140