Behavioural brain research · 2026
Peripheral oxidative stress marker SOD, but not central GSH/GSSG balance, is altered in BDNF heterozygous mice.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Schmidt Michaela, Rossetti Andrea Carlo, Brandwein Christiane, Riva Marco Andrea, Gass Peter, Wiegand Cornelia, Hipler Uta-Christina, Smesny Stefan
Аннотация
BACKGROUND: Brain-derived neurotrophic factor (BDNF) plays a central role in neuronal plasticity and stress-related psychopathology. Alterations in oxidative stress pathways have been proposed as downstream mechanisms of BDNF dysfunction; however, it remains unclear whether BDNF haploinsufficiency primarily affects central or peripheral redox balance.
METHODS: Using a well-characterized mouse model of BDNF haploinsufficiency, we assessed markers of oxidative stress in remaining cerebral cortex tissue and plasma, including superoxide dismutase (SOD) activity and the glutathione redox ratio (GSH/GSSG). Behavioural performance was evaluated using established paradigms of locomotor activity, anxiety-like behaviour, and behavioural habituation. Group differences were analysed using analysis of covariance controlling for sex and prenatal stress exposure. Associations between biochemical markers and behavioural outcomes were examined using Spearman's rank correlation analyses. False discovery rate (FDR) correction according to the Benjamini-Hochberg procedure was applied across all correlation analyses.
RESULTS: BDNF heterozygous mice displayed significantly increased plasma SOD activity compared with wild-type controls, independent of sex and prenatal stress exposure. In contrast, no genotype-dependent differences were observed in brain SOD activity or GSH/GSSG ratios. Peripheral SOD activity was positively associated with plasma phospholipase A₂ (PLA2) activity. Associations between central and peripheral oxidative stress markers did not remain significant after FDR correction. Notably, a robust inverse association was observed between brain SOD activity and the GSH/GSSG ratio. Furthermore, higher brain GSH/GSSG ratios were associated with increased locomotor activity and remained significant after FDR correction, indicating a functional link between central GSH/GSSG balance and behaviour.
CONCLUSIONS: Our findings demonstrate a selective alteration of peripheral antioxidant activity in BDNF haploinsufficiency, while central GSH/GSSG homeostasis remains largely preserved. These results suggest a dissociation between peripheral and central oxidative stress regulation in this model and extend previous evidence linking BDNF-related molecular pathways to systemic biochemical changes.
METHODS: Using a well-characterized mouse model of BDNF haploinsufficiency, we assessed markers of oxidative stress in remaining cerebral cortex tissue and plasma, including superoxide dismutase (SOD) activity and the glutathione redox ratio (GSH/GSSG). Behavioural performance was evaluated using established paradigms of locomotor activity, anxiety-like behaviour, and behavioural habituation. Group differences were analysed using analysis of covariance controlling for sex and prenatal stress exposure. Associations between biochemical markers and behavioural outcomes were examined using Spearman's rank correlation analyses. False discovery rate (FDR) correction according to the Benjamini-Hochberg procedure was applied across all correlation analyses.
RESULTS: BDNF heterozygous mice displayed significantly increased plasma SOD activity compared with wild-type controls, independent of sex and prenatal stress exposure. In contrast, no genotype-dependent differences were observed in brain SOD activity or GSH/GSSG ratios. Peripheral SOD activity was positively associated with plasma phospholipase A₂ (PLA2) activity. Associations between central and peripheral oxidative stress markers did not remain significant after FDR correction. Notably, a robust inverse association was observed between brain SOD activity and the GSH/GSSG ratio. Furthermore, higher brain GSH/GSSG ratios were associated with increased locomotor activity and remained significant after FDR correction, indicating a functional link between central GSH/GSSG balance and behaviour.
CONCLUSIONS: Our findings demonstrate a selective alteration of peripheral antioxidant activity in BDNF haploinsufficiency, while central GSH/GSSG homeostasis remains largely preserved. These results suggest a dissociation between peripheral and central oxidative stress regulation in this model and extend previous evidence linking BDNF-related molecular pathways to systemic biochemical changes.