Copper handling by astrocytes: Insights into neurodegenerative diseases

Tiffany‐Castiglioni, Evelyn; Hong, Sandra; Qian, Yongchang

doi:10.1016/j.ijdevneu.2011.09.004

Cited by 108 publications

(56 citation statements)

References 138 publications

(187 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The precise mechanisms of Cu induced neurotoxicity remains equivocal. Astrocytes has been proposed as the Cu depots of the brain [28] and their involvement in learning and memory consolidation is gaining momentum [29]. Keeping in consideration the pivotal role of astrocytes in many aspects of brain homeostasis, including Cu homeostasis, glutamate and K ?…”

Section: Discussionmentioning

confidence: 99%

“…Keeping in consideration the pivotal role of astrocytes in many aspects of brain homeostasis, including Cu homeostasis, glutamate and K ? ion uptake, spatial buffering, water excretion from brain and defense against oxidative stress; astrocytes has been hypothesized to play a key role in the biochemical and cellular pathology of several neurodegenerative diseases [28]. Cu-intoxication has been shown to increase Cu content of visual cortex and dorsal hippocampus in Wistar rats along with LTP suppression [15].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Regional Distribution of Copper, Zinc and Iron in Brain of Wistar Rat Model for Non-Wilsonian Brain Copper Toxicosis

Pal

Prasad

2015

Ind J Clin Biochem

View full text Add to dashboard Cite

In previous studies, we have reported first in vivo evidence of copper deposition in the choroid plexus, cognitive impairments, astrocytes swelling (Alzheimer type II cells) and astrogliosis (increase in number of astrocytes), and degenerated neurons coupled with significant increase in the hippocampus copper and zinc content in copper-intoxicated Wistar rats. Nonetheless, hippocampus iron levels were not affected by chronic copper-intoxication. Notwithstanding information on distribution of copper, zinc and iron status in different regions of brain due to chronic copper exposure remains fragmentary. In continuation with our previous study, the aim of this study was to investigate the effects of intraperitoneally injected copper lactate (0.15 mg Cu/100 g body weight) daily for 90 days on copper, zinc and iron levels in different regions of the brain using atomic absorption spectrophotometry. Copper-intoxicated group showed significantly increased cortex, cerebellum and striatum copper content (76, 46.8 and 80.7 % increase, respectively) compared to control group. However, non-significant changes were observed for the zinc and iron content in cortex, cerebellum and striatum due to chronic copper exposure. In conclusion, the current study demonstrates that chronic copper toxicity causes differential copper buildup in cortex, cerebellum and striatum region of central nervous system of male Wistar rats; signifying the critical requirement to discretely evaluate the effect of copper neurotoxicity in different brain regions, and ensuing neuropathological and cognitive dysfunctions.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Regional Distribution of Copper, Zinc and Iron in Brain of Wistar Rat Model for Non-Wilsonian Brain Copper Toxicosis

Pal

Prasad

2015

Ind J Clin Biochem

View full text Add to dashboard Cite

show abstract

“…However the mammal central neural system is an information network system with complex structure and function, with, for example, gliocytes accounting for 90% of all cells in the central system filling in between the neurons to provide nutrients and protection for them. The astrocytes especially have the role of maintaining extracellular ion homeostasis, metabolic regulation of neurons, synaptic transmission and plasticity (Dringen et al 2007;Barreto et al 2011;Tiffany-Castiglioni et al 2011). It is known that neurons are generated from early embryonic development until early postnatal stages, while gliogenesis starts at late embryogenesis with low production of both astrocytes and oligodendrocytes that regulate the development of the diverse neurons.…”

Section: Discussionmentioning

confidence: 99%

Expression and localization of the copper-ATPase ATP7A in mice neural cells

Cheng

Guo

Wang

et al. 2015

Italian Journal of Zoology

View full text Add to dashboard Cite

Copper is an essential micronutrient as its redox properties play a significant biochemistry role in the nervous system. Its essentiality is evidenced by Menkes disease (MD), an X-linked neurodegenerative disease caused by mutations in the ATP7A copper transporter, showing that ATP7A is concerned with the development of the nervous system. To investigate the regulation of ATP7A in the development of neurons, we analyzed the expression of the mRNA, protein and the localization of ATP7A in C57BL/6 mice neural stem cells (NSCs), astrocytes and hippocampal neurons cultured in vitro. The results indicated that ATP7A expression was decreased stepwise in NSC, astrocytes and hippocampal neurons. The fluorescent signals of ATP7A were located between the nucleus and plasma membrane in the three kinds of cells. It can be concluded that ATP7A might be involved in the development of neurons and astrocytes. This research may contribute to knowledge about the severe neurodegeneration characteristic of copper-metabolic diseases caused by mutations in the ATP7A gene.

show abstract

“…However, excess copper also possesses toxicity (32); e.g., it has been established that brain copper accumulation is associated with neurodegeneration (33). Previous studies suggested that there might be a close relationship between copper and the progress of Huntington disease (13)(14)(15).…”

Section: Discussionmentioning

confidence: 99%

Huntington disease arises from a combinatory toxicity of polyglutamine and copper binding

Xiao

Fan

Wang

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

130

View full text Add to dashboard Cite

Huntington disease (HD) is a progressive neurodegenerative disorder caused by dominant polyglutamine (polyQ) expansion within the N terminus of huntingtin (Htt) protein. Abnormal metal accumulation in the striatum of HD patients has been reported for many years, but a causative relationship has not yet been established. Furthermore, if metal is indeed involved in HD, the underlying mechanism needs to be explored. Here using a Drosophila model of HD, wherein Htt exon1 with expanded polyQ (Htt exon1-polyQ) is introduced, we show that altered expression of genes involved in copper metabolism significantly modulates the HD progression. Intervention of dietary copper levels also modifies HD phenotypes in the fly. Copper reduction to a large extent decreases the level of oligomerized and aggregated Htt. Strikingly, substitution of two potential copper-binding residues of Htt, Met8 and His82, completely dissociates the copper-intensifying toxicity of Htt exon1-polyQ. Our results therefore indicate HD entails two levels of toxicity: the copper-facilitated protein aggregation as conferred by a direct copper binding in the exon1 and the copper-independent polyQ toxicity. The existence of these two parallel pathways converging into Htt toxicity also suggests that an ideal HD therapy would be a multipronged approach that takes both these actions into consideration.

show abstract

Copper handling by astrocytes: Insights into neurodegenerative diseases

Cited by 108 publications

References 138 publications

Regional Distribution of Copper, Zinc and Iron in Brain of Wistar Rat Model for Non-Wilsonian Brain Copper Toxicosis

Regional Distribution of Copper, Zinc and Iron in Brain of Wistar Rat Model for Non-Wilsonian Brain Copper Toxicosis

Expression and localization of the copper-ATPase ATP7A in mice neural cells

Huntington disease arises from a combinatory toxicity of polyglutamine and copper binding

Contact Info

Product

Resources

About