Effect of perinatally supplemented flavonoids on brain structure, circulation, cognition, and metabolism in C57BL/6J mice. (October 2015)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: Neurochemistry international. Volume 89(2015)
• Page Start: 157
• Page End: 169
• Publication Date: 2015-10
• Subjects: Brain development -- Animal models -- Flavanols -- Cognition -- Inflammation -- Cerebral blood flow; 1H MRS proton MR spectroscopy -- apple+GSE apple + grape seed extract -- ASL arterial spin labeling -- ATP adenosine triphosphate -- AUC auditory cortex -- BBB blood–brain barrier -- BDNF brain derived neurotrophic factor -- CBF cerebral blood flow -- CC corpus callosum -- CD36 cluster of differentiation 36 -- CREB cyclicAMP-response element binding -- CRLB Cramér-Rao lower bounds -- DAB-Ni diaminobenzidine-nickel -- DCX doublecortin -- DEPC diethylpyrocarbonate -- DTI diffusion tensor imaging -- EGCG epigallocatechine gallate -- ELISA enzyme-linked immunosorbent assay -- F fornix -- FA fractional anisotropy -- FAIR flow-sensitive alternating inversion recovery -- GAPDH glyceraldehyde 3-phosphate dehydrogenase -- GD gestational day -- GE gradient echo -- Gln glutamine -- Glu glutamate -- Glu+Gln glutamate + glutamine -- GLUT-1 glucose transporter 1 -- GPC glycerophosphocholine -- HC hippocampus -- Iba1 ionized calcium-binding adapter molecule 1 -- IL-1β interleukin-1β -- IL-6 interleukin-6 -- IML inner molecular layer -- MC motor cortex -- MCP-1 monocyte chemoattractant protein-1 -- MD mean diffusivity -- mI myo-Inositol -- mI+Gly myo-Inositol + glycine -- MR magnetic resonance -- MWM Morris water maze -- NAA N-acetylaspartate -- NAAG N-acetylaspartate + N-acetylaspartateglutamate -- OML outer molecular layer -- OT optic tract -- PBS phosphate buffered saline -- PF paraformaldehyde -- PND postnatal day -- PRESS point-resolved spectroscopy sequence -- PSD95 postsynaptic density 95 -- qRT-PCR quantitative real-time polymerase chain reaction -- ROI region of interest -- ROS reactive oxygen species -- RT room temperature -- SC sensory cortex -- SE-EPI spin-echo planar imaging protocol -- SL stratum lucidum -- SR stratum radiatum -- SSC somatosensory cortex -- Tau taurine -- tCho choline + glycerophosphocholine + phosphocholine -- TE echo time -- TNF-α tumor necrosis factor-α -- VC visual cortex -- VEGF vascular endothelial growth factor -- VOI volume of interest; Neurochemistry -- Periodicals; Neurochemistry -- Periodicals; Neurochimie -- Périodiques; Neurochemistry; Periodicals; 612.804205
• DOI: 10.1016/j.neuint.2015.05.002
• Languages: English
• ISSNs: 0197-0186

Abstract

Abstract: 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. Highlights: Dietary flavanols increase locomotion during early development in pubertal mice. Dietary flavanol supplementation alters spatial learning in young adult mice. Dietary flavanols decrease CBF in the thalamus and cortex of young adult mice.