Aging modifies brain region-specific vulnerability to experimental oxidative stress induced by low dose hydrogen peroxide

Crivello, Natalia A.; Rosenberg, Irwin H.; Shukitt‐Hale, Barbara; Bielinski, Donna F.; Dallal, Gerard E.; Joseph, James A.

doi:10.1007/s11357-007-9039-7

Cited by 12 publications

(6 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An oxidized redox environment during aging has been suggested to alter a number of Ca 2+ signaling processes that are important for learning and memory [16,17]. Thus, it is likely that in addition to NMDAR function, overexpression of SOD1 influences other age-sensitive processes including Ca 2+ -dependent regulation of cell excitability [6,31] and downstream signaling [5,8,12]. As such, overexpression of neuronal SOD1 may provide a model for studies on the role of oxidative stress in senescent physiology and the progression of age-related neurodegenerative diseases.…”

Section: Discussionmentioning

confidence: 99%

Role of antioxidant enzymes in redox regulation of N-methyl-D-aspartate receptor function and memory in middle-aged rats

Lee

Kumar

Rani

et al. 2014

Neurobiology of Aging

View full text Add to dashboard Cite

Overexpression of superoxide dismutase 1 (SOD1) in the hippocampus results in age-dependent impaired cognition and altered synaptic plasticity suggesting a possible model for examining the role of oxidative stress in senescent neurophysiology. However, it is unclear if SOD1 overexpression involves an altered redox environment and a decrease in N-methyl-D-aspartate receptor (NMDAR) synaptic function reported for aging animals. Viral vectors were used to express SOD1 and green fluorescent protein (SOD1+GFP), SOD1 and catalase (SOD1+CAT), or GFP alone in the hippocampus of middle-age (17 mo) male Fischer 344 rats. We confirm that SOD1+GFP and SOD1+CAT reduced lipid peroxidation indicating superoxide metabolites were primarily responsible for lipid peroxidation. SOD1+GFP impaired learning, decreased glutathione peroxidase (GPx) activity, decreased glutathione (GSH) levels, decreased NMDAR-mediated synaptic responses, and impaired long-term potentiation (LTP). Co-expression of SOD1+CAT rescued the effects of SOD1 expression on learning, redox measures, and synaptic function suggesting the effects were mediated by excess hydrogen peroxide. Application of the reducing agent dithiolthreitol (DTT) to hippocampal slices increased the NMDAR-mediated component of the synaptic response in SOD1+GFP animals relative to animals that overexpress SOD1+CAT indicating that the effect of antioxidant enzyme expression on NMDAR function was due to a shift in the redox environment. The results suggest that overexpression of neuronal SOD1 and CAT in middle-age may provide a model for examining the role of oxidative stress in senescent physiology and the progression of age-related neurodegenerative diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Role of antioxidant enzymes in redox regulation of N-methyl-D-aspartate receptor function and memory in middle-aged rats

Lee

Kumar

Rani

et al. 2014

Neurobiology of Aging

View full text Add to dashboard Cite

show abstract

“…This may be partially because the double mutant transgenes, APPswe and PS1dE9, cause increased production of reactive oxygen species (ROSs) selectively in the cerebrum. Previous studies have shown that the cerebrum shows the most significant increase of ROSs with age (Baek et al 1999) and the cerebral cortex is the most vulnerable brain regions to ROS insult (Crivello et al 2007). It is also possible that the region-specific accumulation of GFPu in the AD mouse model may reflect distinct cellular susceptibility to the toxicity caused by the expressions of the mutant genes APPswe and PS1deE9 in the mice.…”

Section: Resultsmentioning

confidence: 99%

The Proteasome Function Reporter GFPu Accumulates in Young Brains of the APPswe/PS1dE9 Alzheimer’s Disease Mouse Model

Hettinger

Zhang

et al. 2013

Cell Mol Neurobiol

View full text Add to dashboard Cite

Alzheimer’s disease (AD), the most common cause of dementia, is neuropathologically characterized by accumulation of insoluble fibrous inclusions in the brain in the form of intracellular neurofibrillary tangles and extracellular senile plaques. Perturbation of the ubiquitin-proteasome system (UPS) has long been considered an attractive hypothesis to explain the pathogenesis of AD. However, studies on UPS functionality with various methods and AD models have achieved non-conclusive results. To get further insight into UPS functionality in AD, we have crossed a well-documented APPswe/PS1dE9 AD mouse model with a UPS functionality reporter, GFPu, mouse expressing green fluorescence protein (GFP) fused to a constitutive degradation signal (CL-1) that facilitates its rapid turnover in conditions of a normal UPS. Our western blot results indicate that GFPu reporter protein was accumulated in the cortex and hippocampus but not striatum in the APPswe/PS1dE9 AD mouse model at 4 weeks of age, which is confirmed by fluorescence microscopy and elevated levels of p53, an endogenous UPS substrate. In accordance with this, the levels of ubiquitinated proteins were elevated in the AD mouse model. These results suggest that UPS is either impaired or functionally insufficient in specific brain regions in the APPswe/PS1dE9 AD mouse model at a very young age, long before senile plaque formation and the onset of memory loss. These observations may shed new light on the pathogenesis of AD.

show abstract

“…However, BDNF affects down-stream targets through three alternate routes; the phospholipase C-γ, the phosphoinositide-3 kinase and the extracellular signal-regulated kinase (ERK) regulated pathway; all leading to transcription factor activation [ 33 ]. In vitro, Asc and SVCT2 overexpression have been shown to increase ERK 1/2 phosphorylation [ 37 ] known to be important for long term spatial memory formation [ 65 ] and sensitive to oxidative stress [ 66 ]. Synapsin 1 has several phosphorylation sites, including one activated by ERK 1/2 [ 67 ].…”

Section: Discussionmentioning

confidence: 99%

Early Life Vitamin C Deficiency Does Not Alter Morphology of Hippocampal CA1 Pyramidal Neurons or Markers of Synaptic Plasticity in a Guinea Pig Model

et al. 2018

View full text Add to dashboard Cite

Approximately 15% of the Western world population, including pregnant women and their children, is characterized as vitamin C (vitC) deficient. In guinea pigs, early life vitC deficiency causes spatial memory deficits, decreased hippocampal volume and neuron numbers, in otherwise clinically healthy animals. We hypothesized that vitC deficiency leads to decreased brain-derived neurotrophic factor and synaptic plasticity markers in selected brain areas (frontal cortex, hippocampus and striatum) and cause morphological changes in cornu ammonis 1 pyramidal neurons of the hippocampus either through a direct effect or indirectly by increased oxidative stress. Fifty-seven female guinea pigs were allocated to three groups receiving either 1390, 100 or 0–50 mg vitC/kg feed for 11 weeks. Dietary vitC levels were reflected in the plasma, cortical and adrenal gland levels, however, redox imbalance was only present in the adrenal glands allowing for the investigation of a direct influence of vitC deficiency on the chosen parameters in the brain. Synaptic plasticity markers were not affected in the investigated brain areas and no differences in isolated pyramidal neuron morphology was recorded. Based on our findings, it appears that vitC deficiency may primarily elicit impaired neuronal function through increased levels of oxidative stress.

show abstract

Aging modifies brain region-specific vulnerability to experimental oxidative stress induced by low dose hydrogen peroxide

Cited by 12 publications

References 84 publications

Role of antioxidant enzymes in redox regulation of N-methyl-D-aspartate receptor function and memory in middle-aged rats

Role of antioxidant enzymes in redox regulation of N-methyl-D-aspartate receptor function and memory in middle-aged rats

The Proteasome Function Reporter GFPu Accumulates in Young Brains of the APPswe/PS1dE9 Alzheimer’s Disease Mouse Model

Early Life Vitamin C Deficiency Does Not Alter Morphology of Hippocampal CA1 Pyramidal Neurons or Markers of Synaptic Plasticity in a Guinea Pig Model

Contact Info

Product

Resources

About