Lateralization of hippocampal nitric oxide mediator system in people with Alzheimer disease, multi-infarct dementia and schizophrenia

Krištofíková, Zdena; Kozmiková, Iryna; Hovorková, Petra; Říčný, Jan; Zach, Petr; Majer, E.; Klaschka, Jan; Řı́pová, Daniela

doi:10.1016/j.neuint.2008.06.009

Cited by 28 publications

(39 citation statements)

References 48 publications

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“…In people with AD, the statistically significant shifts to marked L/R asymmetry have been observed in nNOS/eNOS activities and iNOS expression. The changes were uniformly associated with more marked increases in the L side [7]. Our results thus supported previous studies reporting more pronounced impairment of the dominant L hemisphere in AD [1].…”

Section: Introductionsupporting

confidence: 92%

“…The biomarker is usually directly involved in a pathological pathway and its levels positively reflect brain impairment (e.g., iNOS, excessive NO derived from iNOS is the effecter of the inflammatory cascade by contributing to free-radical mediated injury [8]). Our previous results have demonstrated that iNOS expression was not markedly lateralized in the human hippocampi of nondemented controls [7]. Since the dominant L hemisphere is affected earlier or more severely in AD [1], the changes in the ''negative'' physiologically unlateralized biomarker are more marked in the L side and thus associated with increased ''pathological'' asymmetry (Table 4).…”

Section: Discussionmentioning

confidence: 90%

“…In people with AD, the increase especially in the L side (L/R dominance) was found. Lateral changes in enzyme expression were not observed [7] Wistar/Long Evans rat brains: Activities of nNOS estimated in frontal cortexes are expressed as nmoles/30 min/mg of proteins. Results of ANOVA with repeated measures with age as a grouping factor and laterality as a within factor: (1) Wistar rats: age: Human brains: In the hippocampi of non-demented controls, we observed marked R/L asymmetry in eNOS activity.…”

Section: Discussionmentioning

confidence: 98%

“…The reaction was terminated by adding the stop buffer (30 mM HEPES, 3 mM EDTA, pH = 5.5) and by rapid cooling. DOWEX 50WX8-200 (Sigma) was used to separate citrulline from arginine in accordance with our previous study [7].…”

Section: Activities Of Nitric Oxide Synthases (Nos)mentioning

confidence: 99%

“…Secondly, we have investigated the activities/expressions of nitric oxide synthases in the hippocampi of demented people when compared to age-matched controls [7] since all enzyme isoforms (neuronal-nNOS, endothelial eNOS and inducible iNOS) can play a role in the pathogenesis of AD [8]. In the control group, we have found no pronounced asymmetry in nNOS activity/ expression, marked R/L asymmetry in eNOS activity (but not in expression) and mild L/R asymmetry in iNOS activity (but not in its expression).…”

Section: Introductionmentioning

confidence: 99%

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Aging and Lateralization of the Rat Brain on a Biochemical Level

Krištofíková

Říčný

Ort³

et al. 2010

Neurochem Res

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It has been suggested that the lateralization of the human brain underlies hemispheric specialization and that it can be observed also on a biochemical level. Biochemical laterality appears to be a basis of volumetric or functional asymmetry but direct relationships among them are still unclear. Moreover, age-related differences between the right and left hemispheres are not well documented in various rat strains. In the current study, biochemical markers sensitive to Alzheimer disease (activities of high-affinity choline uptake and of nitric oxide synthases, expression of 17beta-hydroxysteroid dehydrogenase type 10) were estimated in both hemispheres of young and old male Wistar/Long Evans rats. Our experiments indicate (1) differences in some biochemical markers between young Wistar and Long Evans rats (the activities of endothelial nitric oxide synthase are higher in Long Evans and those of citrate synthase in Wistar rats), (2) more similar brain asymmetry of healthy human/young Wistar brains when compared to those of young Long Evans, (3) the decrease in asymmetry of the physiologically left/right lateralized biomarker during aging (the activity of the high-affinity choline uptake decreases more markedly in the left side of old Wistar rats) in accordance with the HAROLD model, (4) the age-related shift to reversed left/right asymmetry of the physiologically right/left lateralized biomarker (the activity of inducible nitric oxide synthase increases especially in the left side of old Long Evans rats), and finally (5) age-related differences in physiologically unlateralized biomarkers between Wistar and Long Evans rats (changes in the activities of neural/endothelial nitric oxide synthases or in expression of 17beta-hydroxysteroid dehydrogenase type 10 are more asymmetrical in old Wistar when compared to rather bilateral alterations of old Long Evans animals). It seems that the physiological lateralization of the human or rat brains on a biochemical level and their age-related alterations are dependent on biomarker type/function. By our opinion, it is difficult, perhaps impossible, to make one simple universal model, at least on a biochemical level. Since lateral analyses are of sufficient sensitivity to reveal subtle links, we recommend using Wistar rather than Long Evans rats in modeling of diseases accompanied by alterations in brain asymmetry.

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Section: Introductionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 98%

Section: Activities Of Nitric Oxide Synthases (Nos)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Aging and Lateralization of the Rat Brain on a Biochemical Level

Krištofíková

Říčný

Ort³

et al. 2010

Neurochem Res

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Proteomics reveal rat hippocampal lateral asymmetry

et al. 2010

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Brain laterality has been observed in animals and humans structurally, functionally, and behaviorally. MRI and CT scans have revealed pathological and normal brain asymmetry. A coarse assessment of rat or human brain fails to expose profound left/right differences, while a finer examination of its structure reveals an array of asymmetric features. This lateralization may be derived from evolutionary, genetic, developmental, epigenetic, and pathologic factors. However, brain structure and function is complex and macroscopic or microscopic asymmetries may be hard to discern from random fluctuations. This study concentrated on the hippocampus and we explored lateralization employing a molecular high-throughput approach. Using proteomic analysis based on a combined approach of 2-D PAGE and MS, we examined differential protein expression in the hippocampi (left vs. right) of young adult male rats. Initial proteomic analysis demonstrated quantitative differences of approximately eighty proteins between the right (RH) and left hippocampus (LH). These were primarily energy-, cell metabolism-, stress-inducible chaperone proteins and cytoskeleton- proteins. Analysis revealed higher abundance of metabolic enzymes related to cellular energy metabolism, in the RH than the LH. In contrast, higher concentrations of proteins which are located mainly in astrocytes were shown in the LH than the RH. Immunoblotting of brain-specific proteins, on single animal hippocampal lysates confirmed the expression of Dynamin-1, DRP2, synapsin-1 and others, to be higher in the RH than LH lysates. These findings demonstrate major laterality in the expression of protein molecules between the two hippocampi providing a fertile field for mapping studies relating molecular, neuroimaging and functional data. Undoubtedly, asymmetries found at the animal level are hard to extrapolate to humans; however, studies in animal models will increase our understanding of the developing and adult brain and the healthy and diseased brain.

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Dynamic study of the hippocampal volume by structural MRI in a rat model of depression

et al. 2014

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The reduction of hippocampal volume remains controversial in depression because of the variability among individuals in clinical studies. Here, a reliable experimental rat model of depression, established by chronic unpredictable mild stress (CUMS), was used. Thirty rats were randomly divided into two groups (CUMS group and control group). Hippocampal volume was dynamically measured every 2 weeks in a 56-day chronic stress procedure using structural magnetic resonance imaging, and the correlation between the hippocampal volume and the learning and memory changes was investigated. Our results demonstrated that CUMS rats showed significantly smaller volumes of the bilateral hippocampus compared to that of the controls, changing dramatically with the development of CUMS procedure. The left hippocampal volume was reduced earlier and more markedly than the right one from the 2nd week to the 8th week of the CUMS procedure (on the 8th week: left: approximately 15.3 %; right: approximately 8.4 % reduction). Additionally, the hippocampal volume of CUMS rats was significantly negatively correlated with the learning and memory changes. Of note, it showed that the more obviously the hippocampal volume reduced, the more severely the learning and memory damaged. In conclusion, the hippocampal volume decreased gradually and dynamically and was correlated with the impairment of the learning and memory in depression.

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Lateralization of hippocampal nitric oxide mediator system in people with Alzheimer disease, multi-infarct dementia and schizophrenia

Cited by 28 publications

References 48 publications

Aging and Lateralization of the Rat Brain on a Biochemical Level

Aging and Lateralization of the Rat Brain on a Biochemical Level

Proteomics reveal rat hippocampal lateral asymmetry

Dynamic study of the hippocampal volume by structural MRI in a rat model of depression

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