Janssen Carola I F, Zerbi Valerio, Mutsaers Martina P C, Jochems Mieke, Vos Claudia A, Vos Julle O, Berg Brian M, van Tol Eric A F, Gross Gabriele, Jouni Zeina E, Heerschap Arend, Kiliaan Amanda J
Department of Anatomy, Donders Institute for Brain, Cognition, and Behaviour, Radboud university medical center, Nijmegen, The Netherlands.
Mead Johnson Pediatric Nutrition Institute, Nijmegen/Evansville, the Netherlands/USA; Mead Johnson Pediatric Nutrition Institute, Evansville, USA.
Neurochem Int. 2015 Oct;89:157-69. doi: 10.1016/j.neuint.2015.05.002. Epub 2015 May 7.
Evidence suggests that flavanol consumption can beneficially affect cognition in adults, but little is known about the effect of flavanol intake early in life. The present study aims to assess the effect of dietary flavanol intake during the gestational and postnatal period on brain structure, cerebral blood flow (CBF), cognition, and brain metabolism in C57BL/6J mice. Female wild-type C57BL/6J mice were randomly assigned to either a flavanol supplemented diet or a control diet at gestational day 0. Male offspring remained on the corresponding diets throughout life and performed cognitive and behavioral tests during puberty and adulthood assessing locomotion and exploration (Phenotyper and open field), sensorimotor integration (Rotarod and prepulse inhibition), and spatial learning and memory (Morris water maze, MWM). Magnetic resonance spectroscopy and imaging at 11.7T measured brain metabolism, CBF, and white and gray matter integrity in adult mice. Biochemical and immunohistochemical analyses evaluated inflammation, synaptic plasticity, neurogenesis, and vascular density. Cognitive and behavioral tests demonstrated increased locomotion in Phenotypers during puberty after flavanol supplementation (p = 0.041) but not in adulthood. Rotarod and prepulse inhibition demonstrated no differences in sensorimotor integration. Flavanols altered spatial learning in the MWM in adulthood (p = 0.039), while spatial memory remained unaffected. Additionally, flavanols increased diffusion coherence in the visual cortex (p = 0.014) and possibly the corpus callosum (p = 0.066) in adulthood. Mean diffusion remained unaffected, a finding that corresponds with our immunohistochemical data showing no effect on neurogenesis, synaptic plasticity, and vascular density. However, flavanols decreased CBF in the cortex (p = 0.001) and thalamus (p = 0.009) in adulthood. Brain metabolite levels and neuroinflammation remained unaffected by flavanols. These data suggest that dietary flavanols results in subtle alterations in brain structure, locomotor activity and spatial learning. Comparison of these data to published findings in aging or neurodegeneration suggests that benefits of dietary flavanols may increase with advancing age and in disease.
有证据表明，摄入黄烷醇对成年人的认知有有益影响，但对于生命早期摄入黄烷醇的影响却知之甚少。本研究旨在评估孕期和产后摄入膳食黄烷醇对C57BL/6J小鼠脑结构、脑血流量（CBF）、认知和脑代谢的影响。在妊娠第0天，将雌性野生型C57BL/6J小鼠随机分为黄烷醇补充饮食组或对照组饮食组。雄性后代终生保持相应饮食，并在青春期和成年期进行认知和行为测试，评估运动和探索能力（表型分析器和旷场试验）、感觉运动整合能力（转棒试验和前脉冲抑制试验）以及空间学习和记忆能力（莫里斯水迷宫，MWM）。在11.7T磁场下进行磁共振波谱和成像，测量成年小鼠的脑代谢、CBF以及白质和灰质完整性。生化和免疫组化分析评估炎症、突触可塑性、神经发生和血管密度。认知和行为测试表明，补充黄烷醇后青春期小鼠在表型分析器试验中的运动增加（p = 0.041），但成年期未增加。转棒试验和前脉冲抑制试验表明感觉运动整合无差异。黄烷醇改变了成年小鼠在莫里斯水迷宫中的空间学习能力（p = 0.039），而空间记忆不受影响。此外，黄烷醇增加了成年小鼠视觉皮层的扩散相干性（p = 0.014），胼胝体可能也有增加（p = 0.066）。平均扩散不受影响，这一发现与我们的免疫组化数据一致，即对神经发生、突触可塑性和血管密度无影响。然而，黄烷醇降低了成年小鼠皮层（p = 0.001）和丘脑（p = 0.009）的CBF。脑代谢物水平和神经炎症不受黄烷醇影响。这些数据表明，膳食黄烷醇会导致脑结构、运动活动和空间学习的细微改变。将这些数据与已发表的关于衰老或神经退行性变的研究结果进行比较表明，膳食黄烷醇的益处可能会随着年龄增长和疾病发展而增加。
