Hyperhomocysteinemia Is a Result, Rather than a Cause, of Depression under Chronic Stress

Chengfeng, Shen; Liu, Wei; Wang, Xinxing; Wu, Lei; Zhan, Rui; Lei, Qian

doi:10.1371/journal.pone.0106625

Cited by 20 publications

(13 citation statements)

References 34 publications

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“…Furthermore, the beneficial effects of B 12 supplementation on hyperhomocysteinemia in aged rats have confirmed the importance of cobalamine in methionine metabolism in the brain (46). Although, numerous studies have pointed to the key role of hyperhomocysteinemia-induced neurotoxicity in various brain regions, recent research has presented the crucial possibility that hyperhomocysteinemia may be just a result of, rather than a cause of, at least some mood disorders, such as depression under chronic stress (47).…”

Section: Discussionmentioning

confidence: 89%

The Effects of Methionine-Enriched and Vitamins (Folate, Pyridoxine and Cobalamine)-Deficient Diet on Exploratory Activity in Rats - A Brief Report

Mijailović

Selaković

Joksimović

et al. 2017

Serbian Journal of Experimental and Clinical Research

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Th e aim of this study was to evaluate the impact of increased homocysteine levels induced by methionine nutritional overload (twice as standard) and defi ciency of the vitamins folate, pyridoxine and cobalamine, which plays an important role in homocysteine metabolism in anxiety-related behaviour, expressed by means of exploratory activity in rats. Twenty-three male Wistar albino rats (4 weeks old, 100±15 g body weight) were divided into three groups: control (n=8), methionine-enriched (Meth+, 7.7 g of methionine/kg chow, n=7) and methionine-enriched vitamin-defi cient (Meth+Vit-, 7.7 g of methionine/kg chow, defi cient in folate, pyridoxine and cobalamine -0.08, 0.01 and 0.01 mg/kg, n=8). All animals had free access to food and water for 30 days. Behavioural testing was performed using the elevated plus maze (EPM) test. Standard parameters for vertical exploratory activity, the number of rearings and the number of head-dippings, as well as the total exploratory activity (summarizing overall exploratory activity in the EPM) were signifi cantly reduced following 30 days of methionine nutritional overload (p<0.05, p<0.05 and p<0.01, respectively). A methionine-enriched diet coupled with a reduction in some B vitamins resulted in a more pronounced decline in exploratory drive observed in the EPM test compared to the control (p<0.01). Th e decline in total exploratory activity associated with vitamin defi ciency was signifi cant compared to the Meth+ group (p<0.05). Th e results of this study highlight the important role of homocysteine in the modulation of exploratory activity in rats. Decreased exploratory drive induced by both a methionine-enriched and vitamin-defi cient diet could be attributed to an anxiogenic eff ect of hyperhomocysteinemia.

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Section: Discussionmentioning

confidence: 89%

The Effects of Methionine-Enriched and Vitamins (Folate, Pyridoxine and Cobalamine)-Deficient Diet on Exploratory Activity in Rats - A Brief Report

Mijailović

Selaković

Joksimović

et al. 2017

Serbian Journal of Experimental and Clinical Research

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“…Although it is not clear if hyperhomocysteinemia is a result or a cause of depression induced by stress, many clinical and animal studies indicated that the accumulation of homocysteine has been implicated in the pathogenesis of depression and the increased homocysteine concentration in the plasma might be the result of stress-induced depression [28]. Notably, some reports showed that psychological stress could significantly contribute to high levels of plasma homocysteine [7].…”

Section: Discussionmentioning

confidence: 99%

Association of Increased Maternal Plasma Homocysteine with the Adverse Birth Outcomes Following Prenatal Psychological Stress

Li¹

2017

Int J Pediatr Res

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Objective: Disorders in the expression of plasma homocysteine are significantly related to psychological stress. There is also evidence that prenatal maternal psychological stress could lead to adverse birth outcomes. The present study aimed to determine whether disorders in the expression of plasma homocysteine would be associated with the adverse birth outcomes following prenatal psychological stress (PPS). Methods: We enrolled 60 pregnancy women with PPS and 60 ones without PPS. The 24-item Hamilton Rating Scale for Depression and the 14-item Hamilton Rating Scale for Anxiety were applied to assess all subjects. The score of depression ≥ 20 or the score of anxiety ≥ 14 was defined as PPS. Maternal plasma homocysteine were measured by enzymatic cycling assay. Results: Plasma homocysteine were significantly higher in women with PPS than ones without PPS (27.3 ± 15.0 μmol/L vs. 20.9 ± 14.7 μmol/L, P = 0.019). Birth weight, birth length, head circumference and gestation length were significantly lower in the infants of women with PPS than ones without PPS (2849 ± 740 g vs. 3212 ± 578 g, P = 0.003; 48.0 ± 3.7 cm vs.

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“…However, further studies would be warranted to assess it. Second, considering that CUMS is also a commonly used animal model for depression (Chengfeng et al 2014), we cannot exclude the interference of emotional effects on cognition in our study. Further studies are necessary to explore the interactions between emotion and cognition, and we would also like to check the role of Hcy in other stress models with fewer components of emotional changes.…”

Section: Discussionmentioning

confidence: 99%

The involvement of homocysteine in stress-induced Aβ precursor protein misprocessing and related cognitive decline in rats

Xie

Zhao

et al. 2016

Cell Stress and Chaperones

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Chronic stress is a risk factor in the development of cognitive decline and even Alzheimer's disease (AD), although its underlying mechanism is not fully understood. Our previous data demonstrated that the level of homocysteine (Hcy) was significantly elevated in the plasma of stressed animals, which suggests the possibility that Hcy is a link between stress and cognitive decline. To test this hypothesis, we compared the cognitive function, plasma concentrations of Hcy, and the brain beta-amyloid (Aβ) level between rats with or without chronic unexpected mild stress (CUMS). A lower performance by rats in behavioral tests indicated that a significant cognitive decline was induced by CUMS. Stress also disturbed the normal processing of Aβ precursor protein (APP) and resulted in the accumulation of Aβ in the brains of rats, which showed a positive correlation with the hyperhomocysteinemia (HHcy) that appeared in stressed rats. Hcytargeting intervention experiments were used to verify further the involvement of Hcy in stress-induced APP misprocessing and related cognitive decline. The results showed that dietinduced HHcy could mimic the cognitive impairment and APP misprocessing in the same manner as CUMS, while Hcy reduction by means of vitamin B complex supplements and betaine could alleviate the cognitive deficits and dysregulation of Aβ metabolism in CUMS rats. Taken together, the novel evidence from our present study suggests that Hcy is likely to be involved in chronic stress-evoked APP misprocessing and related cognitive deficits. Our results also suggested the possibility of Hcy as a target for therapy and the potential value of vitamin B and betaine intake in the prevention of stress-induced cognitive decline.

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Hyperhomocysteinemia Is a Result, Rather than a Cause, of Depression under Chronic Stress

Cited by 20 publications

References 34 publications

The Effects of Methionine-Enriched and Vitamins (Folate, Pyridoxine and Cobalamine)-Deficient Diet on Exploratory Activity in Rats - A Brief Report

The Effects of Methionine-Enriched and Vitamins (Folate, Pyridoxine and Cobalamine)-Deficient Diet on Exploratory Activity in Rats - A Brief Report

Association of Increased Maternal Plasma Homocysteine with the Adverse Birth Outcomes Following Prenatal Psychological Stress

The involvement of homocysteine in stress-induced Aβ precursor protein misprocessing and related cognitive decline in rats

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