Characterization of Anti-neuronal Antibody from Serum of Patients with Tourette Syndrome

• Main Authors: Chia-Wei Chen, 陳嘉偉
• Other Authors: Ching-Hsiang Wu
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/89433247604576761425

碩士 === 國防醫學院 === 生物及解剖學研究所 === 92 === Gilles de la Tourette syndrome (TS), a chronic, familial, neuropsychiatric disorder of unknown etiology, is characterized clinically by the presence of motor and vocal tics that wax and wane in severity over time and by the occurrence of a variety of neurobehavioral disturbances including hyperactivity, self-mutilatory behavior, obsessive compulsive behavior, learning disabilities, and conduct disorder. Current evidence supported a pathophysiologic mechanism involving synaptic neurotransmission, with the dopaminergic system as a primary candidate and the cholinergic system conceivably implicated in the disease. Endorphins and enkephalins are the predominant group of opioids also involved in the development of TS. Despite strong circumstantial evidence that the pathophysiology of TS involved structural and functional disturbances of the basal ganglia, dysfunction at the midbrain and hypothalamus levels was likely to underlie the major symptoms of Tourette's syndrome. Furthermore, various steroid hormones have been suggested to play an important role in the symptom expression of TS and that androgenic hormones, in particular, were probably to exacerbate symptoms of the disorder. Based on MRI, positron emission tomography (PET), and single photon emission computed tomography (SPECT), data alterations in the cortico-striato-pallido-thalamo-cortical functional systems have been provided. Within these systems, dopaminergic neurotransmission was further confirmed to play an important role in the pathophysiology of TS. In the other aspect, autoimmunological mechanisms seem to be important in some subtypes of TS that may be triggered or exacerbated by infections with hemolytic streptococci through the process of molecular mimicry, whereby antibodies directed against bacterial antigens cross-react with brain targets. Indeed, anti-neuronal antibodies have been found in an elevated level in the sera of children with tic disorders and recognizing human basal ganglia, neuroblastoma cell line and rat striatum. Western blot analyses on different brain targets also showed that numerous molecular weight values contributed to differences between TS and controls. Moreover, microinfusion of TS sera or IgG into rat striatum selectively bound to striatal neurons and resulted in oral stereotypies and episodic utterances. However, the specific binding of anti-neuronal antibodies to postmortem tissues and cell line remains doubtful. The selective binding of anti-neuronal antibodies from microinfused TS sera may be resulted from the uptake of living striatal neurons. Our present study using immunohistochemical labelling and fixed rat brain tissues showed the selective binding rather than uptake of TS-serum to neurons in several brain regions. In vitro immunocytochemical staining further confirmed the specific binding of TS-serum to striatal neurons. Our western blot analysis demonstrated the specific high molecule weight proteins particularly 120 kD in the sera of patients with Tourette syndromes when compared with those sera from healthy persons. Further examination of TS-sera using 2D electrophoresis analysis showed differential protein expression of TS-sera from that of healthy persons. After sufficient evidences accumulated especially data from TS family, a genetic vulnerability in TS pathogenesis was proposed.