The mechanisms for the regulation of synaptic dopamine （DA） include its release from presynaptic vesicles, its interaction with post-synaptic and pre-synaptic DA receptors, the reuptake of DA, via dopamine transport...The mechanisms for the regulation of synaptic dopamine （DA） include its release from presynaptic vesicles, its interaction with post-synaptic and pre-synaptic DA receptors, the reuptake of DA, via dopamine transporter （DAT）, the diffusion of DA and its metabolism by mono-amine oxidase （MAO） and cate- chol-O-methyl transferase （COMT）. DA controls complex and specialized functions including, movements, behavior, mood, perception, reward, and more recently, neurogenesis （Popolo et al., 2004; Reimer et al., 2013） and neuroregeneration （Hoglinger et al., 2004; Yang et al., 2008）. These functions are varied and of high fidelity. Movement, as an example, requires regulatory mechanisms for initiating, stopping, slowing-down speed- ing-up, changing directions, for governing the relentless urges to move in the young and sedentariness in the old as well as in motor-freezing, catalepsy, tremor and stereotypy.展开更多
Striatal neurons can be either projection neurons or interneurons, with each type exhibiting distinct susceptibility to various types of brain damage. In this study, 6-hydroxydopamine was injected into the right media...Striatal neurons can be either projection neurons or interneurons, with each type exhibiting distinct susceptibility to various types of brain damage. In this study, 6-hydroxydopamine was injected into the right medial forebrain bundle to induce dopamine depletion, and/or ibotenic acid was injected into the M1 cortex to induce motor cortex lesions. Immunohistochemistry and western blot assay showed that dopaminergic depletion results in significant loss of striatal projection neurons marked by dopamine- and cyclic adenosine monophosphate-regulated phosphoprotein, molecular weight 32 k Da, calbindin, and μ-opioid receptor, while cortical lesions reversed these pathological changes. After dopaminergic deletion, the number of neuropeptide Y-positive striatal interneurons markedly increased, which was also inhibited by cortical lesioning. No noticeable change in the number of parvalbumin-positive interneurons was found in 6-hydroxydopamine-treated rats. Striatal projection neurons and interneurons show different susceptibility to dopaminergic depletion. Further, cortical lesions inhibit striatal dysfunction and damage induced by 6-hydroxydopamine, which provides a new possibility for clinical treatment of Parkinson＇s disease.展开更多
文摘The mechanisms for the regulation of synaptic dopamine （DA） include its release from presynaptic vesicles, its interaction with post-synaptic and pre-synaptic DA receptors, the reuptake of DA, via dopamine transporter （DAT）, the diffusion of DA and its metabolism by mono-amine oxidase （MAO） and cate- chol-O-methyl transferase （COMT）. DA controls complex and specialized functions including, movements, behavior, mood, perception, reward, and more recently, neurogenesis （Popolo et al., 2004; Reimer et al., 2013） and neuroregeneration （Hoglinger et al., 2004; Yang et al., 2008）. These functions are varied and of high fidelity. Movement, as an example, requires regulatory mechanisms for initiating, stopping, slowing-down speed- ing-up, changing directions, for governing the relentless urges to move in the young and sedentariness in the old as well as in motor-freezing, catalepsy, tremor and stereotypy.
基金supported by the National Natural Science Foundation of China,No.81471288
文摘Striatal neurons can be either projection neurons or interneurons, with each type exhibiting distinct susceptibility to various types of brain damage. In this study, 6-hydroxydopamine was injected into the right medial forebrain bundle to induce dopamine depletion, and/or ibotenic acid was injected into the M1 cortex to induce motor cortex lesions. Immunohistochemistry and western blot assay showed that dopaminergic depletion results in significant loss of striatal projection neurons marked by dopamine- and cyclic adenosine monophosphate-regulated phosphoprotein, molecular weight 32 k Da, calbindin, and μ-opioid receptor, while cortical lesions reversed these pathological changes. After dopaminergic deletion, the number of neuropeptide Y-positive striatal interneurons markedly increased, which was also inhibited by cortical lesioning. No noticeable change in the number of parvalbumin-positive interneurons was found in 6-hydroxydopamine-treated rats. Striatal projection neurons and interneurons show different susceptibility to dopaminergic depletion. Further, cortical lesions inhibit striatal dysfunction and damage induced by 6-hydroxydopamine, which provides a new possibility for clinical treatment of Parkinson＇s disease.
