Age-related gene expression changes in substantia nigra dopamine neurons of the rat

Parkinson, Gemma M.; Dayas, Christopher V.; Dw, Smith

doi:10.1016/j.mad.2015.06.002

Cited by 18 publications

(13 citation statements)

References 103 publications

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“…More controlled animal models have found some mixed results. Rat models of aging did not show this variation in DRD1 expression by age, though other genes that contribute to dopamine activity (such as NURR1 , GCH1 , NTRK2 , and GFRA1 ) showed a relationship to aging [ 15 ]. Mouse models of aging demonstrate a relationship with DRD2 expression but not with other dopamine receptors [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Expression of Dopamine-Related Genes in Four Human Brain Regions

Stanfill

Cao

2020

Brain Sciences

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A better understanding of dopaminergic gene expression will inform future treatment options for many different neurologic and psychiatric conditions. Here, we utilized the National Institutes of Health’s Genotype-Tissue Expression project (GTEx) dataset to investigate genotype by expression associations in seven dopamine pathway genes (ANKK1, DBH, DRD1, DRD2, DRD3, DRD5, and SLC6A3) in and across four human brain tissues (prefrontal cortex, nucleus accumbens, substantia nigra, and hippocampus). We found that age alters expression of DRD1 in the nucleus accumbens and prefrontal cortex, DRD3 in the nucleus accumbens, and DRD5 in the hippocampus and prefrontal cortex. Sex was associated with expression of DRD5 in substantia nigra and hippocampus, and SLC6A3 in substantia nigra. We found that three linkage disequilibrium blocks of SNPs, all located in DRD2, were associated with alterations in expression across all four tissues. These demographic characteristic associations and these variants should be further investigated for use in screening, diagnosis, and future treatment of neurological and psychiatric conditions.

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Section: Discussionmentioning

confidence: 99%

Expression of Dopamine-Related Genes in Four Human Brain Regions

Stanfill

Cao

2020

Brain Sciences

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“…Furthermore, they identified a significant age-dependent decline in the number of Nurr1-immunoreactive neurons in the substantia nigra of middle-aged and aged individuals compared with in young subjects ( 19 ). In aged rats, Nurr1 gene expression has been reported to be significantly decreased by 33% in dopaminergic neurons of the substantia nigra ( 20 ); as such, it was suggested that age-dependent decrease of Nurr1 in dopaminergic neurons may be associated with impairment of nigrostriatal signaling and compromised motor function with age ( 20 ). In addition, it has been reported that heterozygous Nurr1 knockout mice exhibit accelerated age-dependent reduction in the number of dopaminergic neurons and impaired dopamine signaling compared with wild-type littermate controls ( 30 ).…”

Section: Discussionmentioning

confidence: 99%

“…A number of studies on Nurr1 have been performed in dopaminergic neurons, and significant decrease in Nurr1 expression has been reported in dopaminergic neurons of the substantia nigra in aged humans and rats ( 19 , 20 ). However, whether there is age-related change of Nurr1 expression in the hippocampus, a region which has been associated with neurogenesis and neural activity ( 21 ), is yet to be fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

Age‑dependent decrease of Nurr1 protein expression in the gerbil hippocampus

et al. 2018

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Nuclear receptor related-1 protein (Nurr1) serves important roles in hippocampal-dependent cognitive process. In the present study, the protein expression of Nurr1 was compared in the hippocampi of young [postnatal month 3 (PM 3)], adult (PM 12) and aged (PM 24) gerbils using western blot analysis and immunohistochemistry. Results indicated that the protein level of Nurr1 was significantly and gradually decreased in the gerbil hippocampus with increasing age. In addition, strong Nurr1 immunoreactivity was primarily observed in pyramidal neurons and granule cells of the hippocampus in the young group, which was determined to be reduced in the adult group and to a greater extent in the aged group. Collectively the data demonstrated that Nurr1 immunoreactivity was gradually and markedly decreased during normal aging. These results indicate that gradual decrease of Nurr1 expression in the hippocampus may be associated with the normal aging process and a decline in hippocampus-dependent cognitive function.

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“…Aging leads to a reduction in DA content in the striatum and SN of humans [38], and reduction in the expression of age-related genes, including TrkB, which is involved in SN DAergic neuronal function and survival, and is associated with motor impairments in PD, which occur due to aging. The Fischer 344 (F344) rat model showed a significant decrease in TrkB expression in the DAergic neurons of SN [39]. Moreover, telomere shortening was also found to be linked to PD.…”

Section: Correlation Between Bdnf/trkb Signaling and Pdmentioning

confidence: 99%

Regulation of BDNF-TrkB Signaling and Potential Therapeutic Strategies for Parkinson’s Disease

Jin

2020

JCM

126

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Brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase receptor type B (TrkB) are widely distributed in multiple regions of the human brain. Specifically, BDNF/TrkB is highly expressed and activated in the dopaminergic neurons of the substantia nigra and plays a critical role in neurophysiological processes, including neuro-protection and maturation and maintenance of neurons. The activation as well as dysfunction of the BDNF-TrkB pathway are associated with neurodegenerative diseases. The expression of BDNF/TrkB in the substantia nigra is significantly reduced in Parkinson’s Disease (PD) patients. This review summarizes recent progress in the understanding of the cellular and molecular roles of BNDF/TrkB signaling and its isoform, TrkB.T1, in Parkinson’s disease. We have also discussed the effects of current therapies on BDNF/TrkB signaling in Parkinson’s disease patients and the mechanisms underlying the mutation-mediated acquisition of resistance to therapies for Parkinson’s disease.

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Age-related gene expression changes in substantia nigra dopamine neurons of the rat

Cited by 18 publications

References 103 publications

Expression of Dopamine-Related Genes in Four Human Brain Regions

Expression of Dopamine-Related Genes in Four Human Brain Regions

Age‑dependent decrease of Nurr1 protein expression in the gerbil hippocampus

Regulation of BDNF-TrkB Signaling and Potential Therapeutic Strategies for Parkinson’s Disease

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