The effects of nigrostriatal dopamine depletion on the thalamic parafascicular nucleus

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• 作者：Sheila V. Kusnoor^a ; ^c ; Michael Bubser^a ; Ariel Y. Deutch^a ; ^b ; ^c ; ^{ariel.deutch@vanderbilt.edu}
• 关键词：6-OHDA ; 6-hydroxydopamine ; BDA ; biotinylated dextran amine ; CeM ; central medial thalamic nucleus ; CL ; central lateral thalamic nucleus ; CM ; centromedian thalamic nucleus ; DAT ; dopamine transporter ; DBH ; dopamine 尾-hydroxylase ; FG ; FluoroGold ; FJC ; Fluoro
• 刊名：Brain Research
• 出版年：2012
• 期刊代码：8_00068993
• 类别：neu
• 出版时间：29 March, 2012
• 卷：1446
• 期：Complete
• 页码：46-55
• 文件大小：799 K

摘要

Neuronal loss in Parkinson's Disease (PD) is seen in a number of brain regions in addition to the substantia nigra (SN). Among these is the thalamic parafascicular nucleus (PF), which sends glutamatergic projections to the striatum and receives GABAergic inputs from the SN. Recent data suggest that lesions of nigrostriatal dopamine axons cause a loss of PF neurons, which has been interpreted to suggest that the PF cell loss seen in PD is secondary to dopamine denervation. However, the extent of a PF dopamine innervation in the rat is unclear, and it is possible that PF cell loss in parkinsonism is independent of nigrostriatal dopamine degeneration. We characterized the dopamine innervation of the PF in the rat and determined if 6-hydroxydopamine SN lesions cause PF neuron degeneration. Dual-label immunohistochemistry revealed that almost all tyrosine hydroxylase-immunoreactive (TH-ir) axons in the PF also expressed dopamine-beta-hydroxylase and were therefore noradrenergic or adrenergic. Moreover, an antibody directed against dopamine revealed only very rare PF dopaminergic axons. Retrograde-tract tracing鈥攊mmunohistochemistry did not uncover an innervation of the PF from midbrain dopamine neurons. Nigrostriatal dopamine neuron lesions did not elicit degeneration of PF cells, as reflected by a lack of FluoroJade C staining. Similarly, neither unilateral 6-OHDA lesions of nigrostriatal axons nor the dorsal noradrenergic bundle decreased the number of PF neurons or the number of PF neurons retrogradely-labeled from the striatum. These data suggest that the loss of thalamostriatal PF neurons in Parkinson's Disease is a primary event rather than secondary to nigrostriatal dopamine degeneration.