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A Study on Neurobiological Mechanism of repetitive Transcranial Magnetic Stimulation in Treating Neuropsychiatry Disorders

Author: LinHong
Tutor: JuGong
School: Fourth Military Medical University
Course: Neurobiology
Keywords: Nervous and Mental Diseases Neurobiology Repetitive transcranial magnetic stimulation Mechanism Immunoreactive Globus pallidus TE671 cells Basal ganglia Low-frequency Striatal neurons
CLC: R741.05
Type: PhD thesis
Year: 2001
Downloads: 109
Quote: 1
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Abstract


Repetitive transcranial magnetic stimulation (rTMS) has been widely used as a research tool to study aspects of human brain physiology including motor function, vision, language and pathophysiology of brain disorders. In recent years, rTMS has also been used as a therapeutic tool in a variety of neuropsychiatry disorders such as Parkinson disease and depression that were conceptualized in term of a dysfuction of neuronal circuits and neurons at a cellular and molecular level. However, the mechanism is unclear. To understand how magnetic stimuli induced by rTMS interact with central nervous system such as neuronal gene activity, neurotransmitter or modulator regulation and structure alterations are necessary.The basal ganglia circuitry processes the signals flow from the cortex, allowing the correct execution of voluntary movements. In Parkinson’s disease, the degeneration of dopaminergic neurons of substantia nigra pars compacta triggers a cascade of functional changes affecting the whole basal ganglia network especially the output nuclei of the circuit. Another possible function of the basal ganglia is gating sensorimotor processing as hippocampus plays, and involves in controlling many behavioral activities such as cognition and memory.In present study, we firstly observe the effect of long-term rTMS on FosB expressions in normal and 6-OHDA lesioned striatum immunohistochmically. Theresult shows, high FosB expressions are induced in the striatum of rTMS treated rats, especially in the rostral ventral striatum and caudal putamen. There is an apparent upregulation of FosB expression in the dorsalateral caudate putamen of 6-OHDA lesioned side after rTMS. In controlled animals, striatal cells do not express FosB- like immunoreactivity except few positive neurons appear in 6-OHDA lesioned side.We also find that high and deeply stained FosB expressions which most possibly are the stable variants of FosB?A FosB are induced in hippocampus of experimental rats, mainly locate in the granule cell layer of dentate gyrus and pyramidal cell layer of CA1 area. No FosB immunoreactive nuclei can be seen in CA2 and CA3 areas. In controlled animals, few and slightly stained FosB positive neurons are found in the granule cell layer of dentate gyrus, but no FosB expressions appear in CA1, CA2 and CA3 areas.Tyrosine hydroxylase (TH) is an important neurotransmitter in basal ganglia circuitry, and plays the role in inducing corticostriatal long-term depression (LTD). In Parkinson’s disease, endogenous dopamine in basal ganglia output nucleus especially external globus pallidus reduces, which induces the ability of intracortical inhibition decrease and then abnormal movement turns up. It has been approved that low frequency of repetitive transcranial magnetic stimulation can depress the motor cortex excitability. In current study, we investigate the changes of TH immunostaining in globus pallidus (GP) and substantia nigra (SN). Compared with that in control group, high TH positive projections are induced in the GP of experimental rats, especially in the external part of GP (GPe). No significant difference of the numbers of TH-positive cells in substantia nigra pars compacta (SNC) and pars reticulata (SNR) in both groups, but TH-positive projections inSNR and lateral substantia nigra (SNL) of rTMS group animals increase than that in sham stimulation group and cells stain darkly in rTMS group.Newly report showed that brain derived neurotrophin factor (BDNF) not only controlled the growth and survival of neurons, but also had another task: boosting the expression of dopamine D3 receptors that allowed neurons to respond to the neurotransmitter dopamine. BDNF reduced in neurodegenerative disorders such as Alzheimer disease and Parkinson’s disease, and significant behavioral improvement could be induced when BDNF were applied. The effects of long-term of rTMS on the BDNF expression in normal and 6-OHDA lesioned basal ganglia are studied in present research. Significant increase of large BDNF immunoreactive gr

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