Effects of cadmium on <i>Bcl-2</i>/<i>Bax</i> expression ratio in rat cortex brain and hippocampus

Mahdavi, Seyed Mohammad; Khodarahmi, Parvin; Roodbari, Nasim Hayati

doi:10.1177/0960327117703687

Cited by 46 publications

(18 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, our findings of lower cadmium levels in Brodmann's area 10 from patients with bipolar disorders is in contrast to a prior study reporting higher levels of this biometal in urine and blood of patients with the disorder (González-Estecha et al, 2011). However, combining our data with these peripheral data supports an argument that low levels of cadmium in CNS are caused by excess excretion of the biometal in patients with bipolar disorders and could be relevant given its role in controlling cortical apoptosis (Mahdavi et al, 2017), the actions of estrogen (Aquino et al, 2012) and the functioning of calcium channels (Hinkle et al, 1992), all of which are reported as being altered in patients with the disorder (Fountoulakis and Vieta, 2008;Group, 2011;Kim et al, 2010).…”

Section: Discussioncontrasting

confidence: 66%

Changes in cortical protein markers of iron transport with gender, major depressive disorder and suicide

Dean

Tsatsanis

Lam

et al. 2019

The World Journal of Biological Psychiatry

View full text Add to dashboard Cite

Background: Changes in levels of metals have been suggested to contribute to the pathophysiologies of several neurodegenerative disorders but to our knowledge this is the first metallomic study in CNS from patients with mood disorders. The focus of this study was on cortical regions affected by the pathophysiologies of bipolar disorders and major depressive disorders. Methods: Levels of metals were measured using inductively coupled plasma mass spectrometry in Brodmann's areas (BA) 6, 10 and 17 from patients with major depressive disorders (n = 13), bipolar disorders (n = 12) and age / sex matched controls (n = 13). Results: There were lower levels of cortical strontium (BA 6 & 10), ruthenium (BA 6 & 17) and cadmium (BA 10) from patients with major depressive disorder as well as lower levels of strontium in BA 10 from patients with bipolar disorders. Unexpectedly, there were changes in levels of 16 metals in the cortex, mainly BA 6, from suicide completers compared to those who died of other causes. Limitations: Cohort sizes were relatively small but comparable to the majority ofwith many studies using human postmortem CNS. Like all studies on non-treatment naïve patients, drug treatment was a potential confound in our experiments. Conclusions: Our exploratory study suggests there are changes in levels of metals in bipolar disorders and major depressive disorders which could be affecting cortical may have implications with regards to the oxidative balance in the cortex of patients with mood disorders. Our data raises the possibility that measuring levels of also suggest exploring specific biometals in the blood metalome could be useful used as a biomarkers for increased risk of suicide.

show abstract

Section: Discussioncontrasting

confidence: 66%

Changes in cortical protein markers of iron transport with gender, major depressive disorder and suicide

Dean

Tsatsanis

Lam

et al. 2019

The World Journal of Biological Psychiatry

View full text Add to dashboard Cite

show abstract

Section: Discussioncontrasting

confidence: 66%

Cortical biometals: Changed levels in suicide and with mood disorders

Dean

Lam

Scarr

et al. 2019

Journal of Affective Disorders

View full text Add to dashboard Cite

Background: Changes in levels of metals have been suggested to contribute to the pathophysiologies of several neurodegenerative disorders but to our knowledge this is the first metallomic study in CNS from patients with mood disorders. The focus of this study was on cortical regions affected by the pathophysiologies of bipolar disorders and major depressive disorders. Methods: Levels of metals were measured using inductively coupled plasma mass spectrometry in Brodmann's areas (BA) 6, 10 and 17 from patients with major depressive disorders (n = 13), bipolar disorders (n = 12) and age / sex matched controls (n = 13). Results: There were lower levels of cortical strontium (BA 6 & 10), ruthenium (BA 6 & 17) and cadmium (BA 10) from patients with major depressive disorder as well as lower levels of strontium in BA 10 from patients with bipolar disorders. Unexpectedly, there were changes in levels of 16 metals in the cortex, mainly BA 6, from suicide completers compared to those who died of other causes. Limitations: Cohort sizes were relatively small but comparable with many studies using human postmortem CNS. Like all studies on non-treatment naïve patients, drug treatment was a potential confound in our experiments. Conclusions: Our exploratory study suggests changes in levels of metals in bipolar disorders and major depressive disorders could be affecting cortical oxidative balance in patients with mood disorders. Our data raises the possibility that measuring levels of specific biometals in the blood could be used as a biomarker for increased risk of suicide.Abstract.docx [Abstract]

show abstract

“…Generally, although Cd +2 is a redox‐inactive metal, it can cross the blood‐brain barrier and induces intrinsic cell death by generation of high quantities of ROS through inhibition of antioxidant enzymes by bindings to their cysteine residue, perturbation of iron homeostasis, and inhibition of mitochondria oxidative phosphorylation . Hence, the associated memory loss with intoxication with memory loss associated with Cd +2 ions is currently attributed to the increased cellular apoptosis of cholinergic and noncholinergic neurons and the subsequent drop in acetylcholine (Ach) levels .…”

Section: Discussionmentioning

confidence: 99%

“…To investigate if SIRT1 is an upstream regulator of AMPK and Akt, we Generally, although Cd +2 is a redox-inactive metal, it can cross the blood-brain barrier and induces intrinsic cell death by generation of high quantities of ROS through inhibition of antioxidant enzymes by bindings to their cysteine residue, perturbation of iron homeostasis, and inhibition of mitochondria oxidative phosphorylation. 35,36 Hence, the associated memory loss with intoxication with memory loss associated with Cd +2 ions is currently attributed to the increased cellular apoptosis of cholinergic and noncholinergic neurons and the subsequent drop in acetylcholine (Ach) levels. 37,38 Indeed, we have recently shown that CdCl 2 -treated rats exhibit lower levels of Ach and activity of choline acyl transferase and increase the activity of Ach esterase (AchE) in their brain homogenates.…”

Section: Sirt1 Is Located Upstream Ampk and Akt Through Treatment Wmentioning

confidence: 99%

Resveratrol protects against cadmium chloride‐induced hippocampal neurotoxicity by inhibiting ER stress and GAAD 153 and activating sirtuin 1/AMPK/Akt

Shati

2019

Environmental Toxicology

View full text Add to dashboard Cite

This study investigated whether the apoptotic effect induced by cadmium chloride (CdCl2) in rat's hippocampi and neuroprotection afforded by resveratrol (RES) are mediated by modulation of ER stress and involve sirtuin 1 (SIRT1)/AMPK/Akt axis. Adult male Wistar rats were divided into four groups (n = 24/group) as control, control + RES (300 mg/kg), CdCl2 (5 mg/kg), and CdCl2 + RES. All treatments were conducted orally for 45 days. Also, cultured hippocampal cells were treated with CdCl2 in the presence or absence of RES and with or without preincubation with SIRT1, AMPK, or PI3K inhibitors. CdCl2 impaired retention and spatial memories of rats and reduced levels and activities of SIRT1 and inhibited AMPK/Akt axis in their hippocamapi where SIRT1 was the upstream regulator. It also enahnced hippocampal levels of reactive oxygen species (ROS) and expression of caspase‐12 and caspase‐3, depleted glutathione (GSH) levels, and activated GRP78, activating transcription factor‐6, GAAD 153, X‐box binding protein‐1 arms of ER stress. On the contrary, RES coadminsitration completley abolished all these events. Interstingly and in control rats, RES not only increased levels of GSH, but also enhenced protein levels of B‐cell lymphoma 2 (Bcl‐2) and dwonregulated GAAD 153. In both control and CdCl2‐treated rats, pharmacological inhibtion of SIRT1, AMPK, and Akt compleltely abolished all effects afforded by RES. In conclusion, CdCl2‐induced hippocampal apopotis is associated with reduction of SIRT1/AMPK/Akt activity levels, ROS generation, downregulation of Bcl‐2, and activities, activation of ER stress, and GAAD 153, whereas RES is able to reverse these effects through activation of SIRT1/AMPK/Akt.

show abstract

Effects of cadmium on Bcl-2/Bax expression ratio in rat cortex brain and hippocampus

Cited by 46 publications

References 52 publications

Changes in cortical protein markers of iron transport with gender, major depressive disorder and suicide

Changes in cortical protein markers of iron transport with gender, major depressive disorder and suicide

Cortical biometals: Changed levels in suicide and with mood disorders

Resveratrol protects against cadmium chloride‐induced hippocampal neurotoxicity by inhibiting ER stress and GAAD 153 and activating sirtuin 1/AMPK/Akt

Contact Info

Product

Resources

About