Evidence for oxidative stress in the frontal cortex in patients with recurrent depressive disorder—a postmortem study

Somatic variation in DNA can cause cells to deviate from the preordained genomic path in both disease and healthy conditions. Here, using exome sequencing of paired tissue samples, we show that the normal human brain harbors somatic single base variations measuring up to 0.48% of the total variations. Interestingly, about 64% of these somatic variations in the brain are expected to lead to non-synonymous changes, and as much as 87% of these represent G:C>T:A transversion events. Further, the transversion events in the brain were mostly found in the frontal cortex, whereas the corpus callosum from the same individuals harbors the reference genotype. We found a significantly higher amount of 8-OHdG (oxidative stress marker) in the frontal cortex compared to the corpus callosum of the same subjects (p<0.01), correlating with the higher G:C>T:A transversions in the cortex. We found significant enrichment for axon guidance and related pathways for genes harbouring somatic variations. This could represent either a directed selection of genetic variations in these pathways or increased susceptibility of some loci towards oxidative stress. This study highlights that oxidative stress possibly influence single nucleotide somatic variations in normal human brain.

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Strawberry Intake Ameliorates Oxidative Stress and Decreases GABA Levels Induced by High-Fat Diet in Frontal Cortex of Rats

Antioxidants ◽

10.3390/antiox8030070 ◽

2019 ◽

Vol 8 (3) ◽

pp. 70 ◽

Cited By ~ 1

Author(s):

Cuauhtémoc Sandoval-Salazar ◽

Cecilia Oviedo-Solís ◽

Edmundo Lozoya-Gloria ◽

Herlinda Aguilar-Zavala ◽

Martha Solís-Ortiz ◽

...

Keyword(s):

Oxidative Stress ◽

Lipid Peroxidation ◽

Oxidative Damage ◽

Frontal Cortex ◽

Protein Oxidation ◽

High Fat Diet ◽

High Fat ◽

Gaba Concentration ◽

Obese Rats ◽

Lipid And Protein Oxidation

It has been proposed that there is a correlation between high-fat diet (HFD), oxidative stress and decreased γ-aminobutyric acid (GABA) levels, but this has not been thoroughly demonstrated. In the present study, we determined the effects of strawberry extract intake on the oxidative stress and GABA levels in the frontal cortex (FC) of obese rats. We observed that an HFD increased lipid and protein oxidation, and decreased GABA levels. Moreover, UV-irradiated strawberry extract (UViSE) decreased lipid peroxidation but not protein oxidation, whereas non-irradiated strawberry extract (NSE) reduced protein oxidation but not lipid peroxidation. Interestingly, NSE increased GABA concentration, whereas UViSE was not as effective. In conclusion, our results suggest that an HFD increases oxidative damage in the FC, whereas strawberry extract intake may ameliorate the disturbances associated with HFD-induced oxidative damage.

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Environmental Enrichment Attenuates Oxidative Stress and Alters Detoxifying Enzymes in an A53T α-Synuclein Transgenic Mouse Model of Parkinson’s Disease

Antioxidants ◽

10.3390/antiox9100928 ◽

2020 ◽

Vol 9 (10) ◽

pp. 928

Author(s):

Jung Hwa Seo ◽

Seong-Woong Kang ◽

Kyungri Kim ◽

Soohyun Wi ◽

Jang Woo Lee ◽

...

Keyword(s):

Oxidative Stress ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Olfactory Bulb ◽

Frontal Cortex ◽

Brain Stem ◽

Environmental Enrichment ◽

Brain Regions ◽

Wild Type ◽

Detoxifying Enzymes

Although environmental enrichment (EE) is known to reduce oxidative stress in Parkinson’s disease (PD), the metabolic alternations for detoxifying endogenous and xenobiotic compounds according to various brain regions are not fully elucidated yet. This study aimed to further understand the role of EE on detoxifying enzymes, especially those participating in phase I of metabolism, by investigating the levels of enzymes in various brain regions such as the olfactory bulb, brain stem, frontal cortex, and striatum. Eight-month-old transgenic PD mice with the overexpression of human A53T α-synuclein and wild-type mice were randomly allocated to either standard cage condition or EE for 2 months. At 10 months of age, the expression of detoxifying enzymes was evaluated and compared with wild-type of the same age raised in standard cages. EE improved neurobehavioral outcomes such as olfactory and motor function in PD mice. EE-treated mice showed that oxidative stress was attenuated in the olfactory bulb, brain stem, and frontal cortex. EE also reduced apoptosis and induced cell proliferation in the subventricular zone of PD mice. The overexpression of detoxifying enzymes was observed in the olfactory bulb and brain stem of PD mice, which was ameliorated by EE. These findings were not apparent in the other experimental regions. These results suggest the stage of PD pathogenesis may differ according to brain region, and that EE has a protective effect on the PD pathogenesis by decreasing oxidative stress.

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Brain Biopsy Findings Link Major Depressive Disorder to Neuroinflammation, Oxidative Stress, and Neurovascular Dysfunction: A Case Report

Biological Psychiatry ◽

10.1016/j.biopsych.2013.07.041 ◽

2014 ◽

Vol 75 (12) ◽

pp. e23-e26 ◽

Cited By ~ 14

Author(s):

Souhel Najjar ◽

Daniel M. Pearlman ◽

Scott Hirsch ◽

Kent Friedman ◽

John Strange ◽

...

Keyword(s):

Oxidative Stress ◽

Major Depressive Disorder ◽

Case Report ◽

Depressive Disorder ◽

Brain Biopsy ◽

Major Depressive ◽

Neurovascular Dysfunction

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Regionally specific alterations in functional connectivity of the anterior cingulate cortex in major depressive disorder

Psychological Medicine ◽

10.1017/s0033291712000323 ◽

2012 ◽

Vol 42 (10) ◽

pp. 2071-2081 ◽

Cited By ~ 89

Author(s):

C. G. Davey ◽

B. J. Harrison ◽

M. Yücel ◽

N. B. Allen

Keyword(s):

Major Depressive Disorder ◽

Functional Connectivity ◽

Depressive Disorder ◽

Frontal Cortex ◽

Caudate Nucleus ◽

Anterior Cingulate Cortex ◽

Cingulate Cortex ◽

Anterior Cingulate ◽

Major Depressive ◽

Close Link

BackgroundDepression has been associated with functional alterations in several areas of the cingulate cortex. In this study we have taken a systematic approach to examining how alterations in functional connectivity vary across the functionally diverse subregions of the rostral cingulate cortex.MethodEighteen patients with major depressive disorder, aged 15 to 24 years, were matched with 20 healthy control participants. Using resting-state functional connectivity magnetic resonance imaging (fcMRI), we systematically investigated the functional connectivity of four subregions of the rostral cingulate cortex. Voxelwise statistical maps of each subregion's connectivity with other brain areas were compared between the patient and control groups.ResultsThe depressed participants showed altered patterns of connectivity with ventral cingulate subregions. They showed increased connectivity between subgenual anterior cingulate cortex (ACC) and dorsomedial frontal cortex, with connectivity strength showing positive correlation with illness severity. Depressed participants also showed increased connectivity between pregenual ACC and left dorsolateral frontal cortex, and decreased connectivity between pregenual ACC and the caudate nucleus bilaterally.ConclusionsThe results reinforce the importance of subgenual ACC for depression, and show a close link between brain regions that support self-related processes and affective visceromotor function. The pregenual ACC also has an important role, with its increased connectivity with dorsolateral frontal cortex suggesting heightened cognitive regulation of affect; and reduced connectivity with the caudate nucleus potentially underlying symptoms such as anhedonia, reduced motivation and psychomotor dysfunction.

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