Although the functional neuroanatomy of the midbrain dopamine （mDA） system has been well characterized, the literature regarding its capacity to innervate the hippocampal formation has been inconsistent. The lack of...Although the functional neuroanatomy of the midbrain dopamine （mDA） system has been well characterized, the literature regarding its capacity to innervate the hippocampal formation has been inconsistent. The lack of expression of definitive markers for dopaminergic fibers, such as the dopamine transporter, in the hippocampus has complicated studies in this area. Here we have used immunohistochemical techniques to characterize the tyrosine hydroxylase expressing fiber network in the rat hippocampus, combined with retrograde tracing from the dentate gyrus to assess the capacity for afferent innervation by mDA neurons. The results indicate that virtually all tyrosine hydroxylase fibers throughout the hippocampus are of a noradrenergic phenotype, while the overlying cortex contains both dopaminergic and noradrenergic fiber networks. Furthermore, retrograde tracing from the dentate gyrus robustly labels tyrosine hydroxylase-immunoreactive noradrenergic neurons in the locus coeruleus but not mDA neurons.展开更多
Iron deposition in Parkinson’s disease(PD)is a potential disease-modifying target.We previously showed that supplementation of the iron-exporter,ceruloplasmin,selectively corrected nigral iron elevation in the 1-meth...Iron deposition in Parkinson’s disease(PD)is a potential disease-modifying target.We previously showed that supplementation of the iron-exporter,ceruloplasmin,selectively corrected nigral iron elevation in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)model.Ceruloplasmin delivers iron to transferrin(Tf),the extracellular iron-transporting protein.We show that Tf protein levels are decreased in the nigra of post-mortem PD brains compared with controls(−35%;n=10 each).Because Tf traffics iron away from iron-replete tissues,we hypothesized that Tf supplementation could selectively facilitate iron export from the nigra in PD.In cultured neurons,Tf treatment corrected iron accumulation,and subcutaneous Tf to mice ameliorated iron accumulation and motor deficits in the MPTP model of PD.Although these data support a role for Tf in the disease mechanism for PD,and its potential use for correcting disorders of iron overload,Tf therapy also caused systemic iron depletion,which could limit its application for PD.展开更多
文摘Although the functional neuroanatomy of the midbrain dopamine （mDA） system has been well characterized, the literature regarding its capacity to innervate the hippocampal formation has been inconsistent. The lack of expression of definitive markers for dopaminergic fibers, such as the dopamine transporter, in the hippocampus has complicated studies in this area. Here we have used immunohistochemical techniques to characterize the tyrosine hydroxylase expressing fiber network in the rat hippocampus, combined with retrograde tracing from the dentate gyrus to assess the capacity for afferent innervation by mDA neurons. The results indicate that virtually all tyrosine hydroxylase fibers throughout the hippocampus are of a noradrenergic phenotype, while the overlying cortex contains both dopaminergic and noradrenergic fiber networks. Furthermore, retrograde tracing from the dentate gyrus robustly labels tyrosine hydroxylase-immunoreactive noradrenergic neurons in the locus coeruleus but not mDA neurons.
基金This work was supported by funds from the Australian Research Council,the Australian National Health&Medical Research Council(GNT1100441 and GNT1044542)the CRC for Mental Health and Operational Infrastructure Support Victorian State Government。
文摘Iron deposition in Parkinson’s disease(PD)is a potential disease-modifying target.We previously showed that supplementation of the iron-exporter,ceruloplasmin,selectively corrected nigral iron elevation in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)model.Ceruloplasmin delivers iron to transferrin(Tf),the extracellular iron-transporting protein.We show that Tf protein levels are decreased in the nigra of post-mortem PD brains compared with controls(−35%;n=10 each).Because Tf traffics iron away from iron-replete tissues,we hypothesized that Tf supplementation could selectively facilitate iron export from the nigra in PD.In cultured neurons,Tf treatment corrected iron accumulation,and subcutaneous Tf to mice ameliorated iron accumulation and motor deficits in the MPTP model of PD.Although these data support a role for Tf in the disease mechanism for PD,and its potential use for correcting disorders of iron overload,Tf therapy also caused systemic iron depletion,which could limit its application for PD.
