Spatial cognitive deficits in an animal model of Wernicke–Korsakoff syndrome are related to changes in thalamic VDAC protein concentrations

Bueno, K.O.; Resende, Letícia de Souza; Ribeiro, Andrea Frozino; Santos, Dalton Muniz; Gonçalves, Evonnildo Costa; Vigil, Fabio A; Silva, I.F. de Oliveira; Ferreira, L.F.; Pimenta, Adriano Monteiro de Castro; Ribeiro, Ângela Maria

doi:10.1016/j.neuroscience.2015.03.001

Cited by 12 publications

(8 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, increases in VDAC levels in the thalamus of mice were shown to be associated with neurodegeneration in the Batten disease model [301]. Similarly spatial cognitive deficits in an animal model of Wernicke-Korsakoff syndrome were reported to be associated with changes in thalamic VDAC levels [302]. The involvement of plasmalemmal VDAC in AD was also proposed [62,63].…”

Section: Over-expression Of Vdac1 In Neurodegenerative Diseasesmentioning

confidence: 99%

Mitochondrial Transport Proteins

2022

View full text Add to dashboard Cite

show abstract

Section: Over-expression Of Vdac1 In Neurodegenerative Diseasesmentioning

confidence: 99%

Mitochondrial Transport Proteins

2022

View full text Add to dashboard Cite

show abstract

“…It has been shown that brains from AD patients contain high levels of nitrated VDAC1, pointing to oxidative damage from VDAC1 ( Sultana et al, 2006 ), and feasibly affecting cell energy and metabolite homeostasis ( Ferrer, 2009 ). Moreover high-levels of VDAC1 were demonstrated in the dystrophic neurites of Aβ deposits in the brains of post-mortem AD patients ( Yoo et al, 2001 ; Perez-Gracia et al, 2008 ; Cuadrado-Tejedor et al, 2011 ; Manczak and Reddy, 2012 ), and in the thalamuses of mice with neurodegeneration in the Batten disease model ( Kielar et al, 2009 ), and changes in thalamic VDAC protein levels were found to be related to spatial cognitive deficits in an animal model of Wernicke–Korsakoff syndrome ( Bueno et al, 2015 ). Interestingly, it is also reported that in AD, VDAC1 levels are decreased in the frontal cortex, and VDAC2 is elevated in the temporal cortex ( Rosa and Cesar, 2016 ).…”

Section: Metformin’s Multiple Effects On Various Diseasesmentioning

confidence: 99%

Adverse Effects of Metformin From Diabetes to COVID-19, Cancer, Neurodegenerative Diseases, and Aging: Is VDAC1 a Common Target?

et al. 2021

View full text Add to dashboard Cite

Metformin has been used for treating diabetes mellitus since the late 1950s. In addition to its antihyperglycemic activity, it was shown to be a potential drug candidate for treating a range of other diseases that include various cancers, cardiovascular diseases, diabetic kidney disease, neurodegenerative diseases, renal diseases, obesity, inflammation, COVID-19 in diabetic patients, and aging. In this review, we focus on the important aspects of mitochondrial dysfunction in energy metabolism and cell death with their gatekeeper VDAC1 (voltage-dependent anion channel 1) as a possible metformin target, and summarize metformin’s effects in several diseases and gut microbiota. We question how the same drug can act on diseases with opposite characteristics, such as increasing apoptotic cell death in cancer, while inhibiting it in neurodegenerative diseases. Interestingly, metformin’s adverse effects in many diseases all show VDAC1 involvement, suggesting that it is a common factor in metformin-affecting diseases. The findings that metformin has an opposite effect on various diseases are consistent with the fact that VDAC1 controls cell life and death, supporting the idea that it is a target for metformin.

show abstract

“…VDAC1 can also be located in other subcellular compartments, where its role remains under discussion [ 16 , 17 ], since independent groups found VDAC1 in the plasma membrane [ 18 – 20 ] and endoplasmic reticulum (ER) [ 21 ]. VDAC1 excess has been observed in pathologies of the nervous system associated with cell loss [ 22 – 24 ], such as in the brains of post-mortem AD patients, AD-like transgenic mice [ 25 , 26 ], and other neurodegenerative disease models [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

VDAC1 regulates neuronal cell loss after retinal trauma injury by a mitochondria-independent pathway

et al. 2022

View full text Add to dashboard Cite

The voltage-dependent anion channel 1 (VDAC1) was first described as a mitochondrial porin that mediates the flux of metabolites and ions, thereby integrating both cell survival and death signals. In the nervous system, the functional roles of VDAC1 remain poorly understood. Herein, the rat retina was employed to study VDAC1. First, it was observed that even subtle changes in VDAC1 levels affect neuronal survival, inducing severe alterations in the retinal morphology. We next examined the regulation of VDAC1 after traumatic retinal injury. After mechanical trauma, SOD1 translocates towards the nucleus, which is insufficient to contain the consequences of oxidative stress, as determined by the evaluation of protein carbonylation. Using in vitro models of oxidative stress and mechanical injury in primary retinal cell cultures, it was possible to determine that inhibition of VDAC1 oligomerization by 4′-diisothiocyano-2,2′-disulfonic acid stilbene (DIDS) rescues cell viability, impacting microglial cell activation. We next focused on the regulation of VDAC1 after retinal mechanical injury. VDAC1 was promptly upregulated 2 h after lesion in the plasma membrane and endoplasmic reticulum rather than in the mitochondria, and multimers of VDAC1 were assembled after lesion. DIDS intraocular application decreased apoptosis and prevented microglial polarization, which confirmed in vitro observations. Considering the role of microglia in neuroinflammation, multiplex evaluation of cytokines showed that DIDS application disorganized the inflammatory response 2 h after the lesion, matching the fast regulation of VDAC1. Taken together, data disclosed that fine regulation of VDAC1 influences neuronal survival, and pharmacological inhibition after trauma injury has neuroprotective effects. This protection may be attributed to the effects on VDAC1 abnormal accumulation in the plasma membrane, thereby controlling the activation of microglial cells. We concluded that VDAC1 is a putative therapeutic target in neuronal disorders since it integrates both death and survival cellular signaling.

show abstract

Spatial cognitive deficits in an animal model of Wernicke–Korsakoff syndrome are related to changes in thalamic VDAC protein concentrations

Cited by 12 publications

References 45 publications

Mitochondrial Transport Proteins

Mitochondrial Transport Proteins

Adverse Effects of Metformin From Diabetes to COVID-19, Cancer, Neurodegenerative Diseases, and Aging: Is VDAC1 a Common Target?

VDAC1 regulates neuronal cell loss after retinal trauma injury by a mitochondria-independent pathway

Contact Info

Product

Resources

About