Intracellular zinc mobilization is required for nNOS (+) neuron loss. Role of zinc in the excitotoxic cascade

Alberto GRANZOTTO

doi:https://doi.org/10.37212/jcnos.584662

Makale detayları

Intracellular zinc mobilization is required for nNOS (+) neuron loss. Role of zinc in the excitotoxic cascade

Yazarlar:

Alberto GRANZOTTO

Yayıncı:

Hücresel Sinir Bilimleri ve Oksidatif Stres Derneği

Ana Başlıklar:

İnsan psikolojisi

Dergi:

Journal of Cellular Neuroscience and Oxidative Stress 2019 Vol.11 Issue 0, pp.5-5

Belge Tipi:

Makale

Yayın Tarihi:

6/2019

Belge Dili:

İngilizce

Document ID (Org No.):

2000708753

Sıklık:

Üç Yıllık

eISSN:

2149-7222

DOI:

https://doi.org/10.37212/jcnos.584662

Özet:

 


NMDA receptor (NMDAR) overstimulation by glutamate promotes massive calcium (Ca2+) entry and initiates a cascade of events leading to the overproduction of Reactive Oxygen Species (ROS), mitochondrial dysfunction, intraneuronal zinc (Zn2+) mobilization, and, ultimately, neuronal demise (Choi 1992).  This glutamate-driven form of neuronal death has been described as excitotoxicity (Olney 1969).  NADPH-diaphorase neurons [nNOS (+) neurons] are a subpopulation of nitric-oxide synthase-overexpressing interneurons that is spared from the NMDAR-mediated neuronal death (Koh and Choi, 1988).  The mechanisms underlying the reduced vulnerability of nNOS (+) neurons to NMDAR-driven neuronal death are still largely unexplored.  In the talk, we will discuss the mechanisms that are involved in the reduced vulnerability of nNOS (+) neurons.  Differences between nNOS (+) and nNOS (-) neurons as far as changes in intracellular Ca2+ levels, mitochondrial functioning, ROS production as well as the intraneuronal accumulation of Zn2+ were investigated.  We found that nNOS (+) neurons differ from nNOS (-) cells by lacking the production of a significant amount of ROS in response to NMDAR activation.  The absence of NMDA-driven oxidative stress shown by the nNOS (+) neurons abolished the neurotoxic accumulation of Zn2+.  Exposure of nNOS (-) neurons to NMDA in the presence of TPEN (a Zn2+ chelator) mimicked the behavior of the nNOS (+) subpopulation and preserved the nNOS (-) population from the excitotoxic damage.  These results indicate that Zn2+ mobilization is the mandatory step of the excitotoxic cascade.  These findings identify the intraneuronal accumulation of Zn2+ as a therapeutic target for the treatment of excitotoxic prone neurological conditions. 

.

Makale detayları

Intracellular zinc mobilization is required for nNOS (+) neuron loss. Role of zinc in the excitotoxic cascade

Yazarlar: Alberto GRANZOTTO

Yayıncı: Hücresel Sinir Bilimleri ve Oksidatif Stres Derneği

Ana Başlıklar: İnsan psikolojisi

Dergi: Journal of Cellular Neuroscience and Oxidative Stress 2019 Vol.11 Issue 0, pp.5-5

Belge Tipi: Makale

Yayın Tarihi: 6/2019

Belge Dili: İngilizce

Document ID (Org No.): 2000708753

Sıklık: Üç Yıllık

eISSN: 2149-7222

DOI: https://doi.org/10.37212/jcnos.584662

Sayı

Yazarlar:

Alberto GRANZOTTO

Yayıncı:

Hücresel Sinir Bilimleri ve Oksidatif Stres Derneği

Ana Başlıklar:

İnsan psikolojisi

Dergi:

Journal of Cellular Neuroscience and Oxidative Stress 2019 Vol.11 Issue 0, pp.5-5

Belge Tipi:

Makale

Yayın Tarihi:

6/2019

Belge Dili:

İngilizce

Document ID (Org No.):

2000708753

Sıklık:

Üç Yıllık

eISSN:

2149-7222

DOI:

https://doi.org/10.37212/jcnos.584662