Early life diet containing prebiotics and bioactive whey protein fractions increased dendritic spine density of rat hippocampal neurons

Waworuntu, Rosaline; Hanania, Taleen; Boikess, Steven R.; Rex, Christopher S.; Berg, Brian M.

doi:10.1016/j.ijdevneu.2016.09.001

Cited by 19 publications

(12 citation statements)

References 36 publications

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“…5–7 cells (RSC) or 7–8 cells (HC) were sampled per mouse, and each dendrite was analyzed by 3 independent analysts. Afraxis automated image assignment and spine measurement and classification criteria are described previously 21 and follow an established paradigm 22 . For spine density and spine morphological classification, data across analysts were averaged to report data for each dendrite.…”

Section: Methodsmentioning

confidence: 99%

PDE4D regulates Spine Plasticity and Memory in the Retrosplenial Cortex

Baumgärtel

Green

Hornberger

et al. 2018

Sci Rep

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The retrosplenial cortex (RSC) plays a critical role in episodic memory, but the molecular mechanisms governing plasticity in this structure are poorly understood. Diverse studies have demonstrated a role for RSC in acquisition, early consolidation and retrieval similar to the hippocampus (HC), as well as in systems consolidation similar to the anterior cingulate cortex. Here, we asked whether established molecular and structural substrates of memory consolidation in the HC also engage in RSC shortly after learning. We show striking parallels in training induced gene-activation in HC and RSC following contextual conditioning, which is blocked by systemic administration of an NMDA receptor antagonist. Long-term memory is enhanced by retrosplenial and hippocampal knockdown (KD) of the cAMP specific phosphodiesterase Pde4d. However, while training per se induces lasting spine changes in HC, this does not occur in RSC. Instead, increases in the number of mature dendritic spines are found in the RSC only if cAMP signaling is augmented by Pde4d KD, and spine changes are at least partially independent of training. This research highlights parallels and differences in spine plasticity mechanisms between HC and RSC, and provides evidence for a functional dissociation of the two.

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Section: Methodsmentioning

confidence: 99%

PDE4D regulates Spine Plasticity and Memory in the Retrosplenial Cortex

Baumgärtel

Green

Hornberger

et al. 2018

Sci Rep

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“…LAC also promotes learning and signalling pathways involved in neuroplasticity (Chen et al, 2015). Furthermore, GOS, PDX and LAC combined enhance brain structure (Mudd et al, 2016;Waworuntu et al, 2016). Notably, prebiotics may be more effective in early life (Chen et al, 2015;Mudd et al, 2016;Waworuntu et al, 2016;Williams et al, 2016), when the developing brain (Spear, 2000) and microbiota (Agans et al, 2011;Yatsunenko et al, 2012;Ringel-Kulka et al, 2013) are more plastic.…”

Section: Introductionmentioning

confidence: 99%

Early life diets with prebiotics and bioactive milk fractions attenuate the impact of stress on learned helplessness behaviours and alter gene expression within neural circuits important for stress resistance

Mika

Day

Martinez

et al. 2016

Eur J of Neuroscience

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Manipulating gut microbes may improve mental health. Prebiotics are indigestible compounds that increase the growth and activity of health-promoting microorganisms, yet few studies have examined how prebiotics affect CNS function. Using an acute inescapable stressor known to produce learned helplessness behaviours such as failure to escape and exaggerated fear, we tested whether early life supplementation of a blend of two prebiotics, galactooligosaccharide (GOS) and polydextrose (PDX), and the glycoprotein lactoferrin (LAC) would attenuate behavioural and biological responses to stress later in life. Juvenile, male F344 rats were fed diets containing either GOS and PDX alone, LAC alone, or GOS, PDX and LAC. All diets altered gut bacteria, while diets containing GOS and PDX increased Lactobacillus spp. After 4 weeks, rats were exposed to inescapable stress, and either immediately killed for blood and tissues, or assessed for learned helplessness 24 h later. Diets did not attenuate stress effects on spleen weight, corticosterone and blood glucose; however, all diets differentially attenuated stress-induced learned helplessness. Notably, in situ hybridization revealed that all diets reduced stress-evoked cfos mRNA in the dorsal raphe nucleus (DRN), a structure important for learned helplessness behaviours. In addition, GOS, PDX and LAC diet attenuated stress-evoked decreases in mRNA for the 5-HT autoreceptor in the DRN and increased basal BDNF mRNA within the prefrontal cortex. These data suggest early life diets containing prebiotics and/or LAC promote behavioural stress resistance and uniquely modulate gene expression in corresponding circuits.

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“…MFGM has also been shown to improve cognitive development and performance in preclinical rodent models. Rodents fed MFGM exhibited improved performance on spatial and passive avoidance tasks (40), increased hippocampal spine density (70), and increased hippocampal ATP concentrations concurrent with increases in expression of genes related to mitochondrial electron transport (71). In a dose-response study, rats fed diets containing 1% complex milk lipids (Fonterra Research Center, Palmerston North, New Zealand) had increased exploratory behavior in response to a novel object.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Dietary Bovine Milk Fat Globule Membrane Supplementation on Growth, Serum Cholesterol and Lipoproteins, and Neurodevelopment in the Young Pig

et al. 2019

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Introduction: Milk fat globule membrane (MFGM) is a protein- and phospholipid-rich membrane that surrounds the lipid droplet in milk. We have previously reported that a diet composed of a combination of prebiotics, bovine MFGM (bMFGM), and lactoferrin (bLf) supported brain development in young pigs. Due to the growing interest of its potential benefits in neurodevelopment, the present study focused on the effects of dietary bMFGM alone using the pig as a translational model.Methods: Male pigs were provided ad libitum access to milk replacer with added whey protein-lipid concentrate (source of bMFGM) at 0 (CONT), 2.5 (MFGM-2.5), or 5 (MFGM-5.0) g/L from postnatal day (PND) 2 to 31. Blood was collected from pigs at PND 15 and 31, and pigs underwent behavioral testing using the novel object recognition task starting at PND 25. At PND 31, magnetic resonance imaging was conducted and animals were subsequently euthanized for tissue collection.Results: No group differences in body weight gain or milk intake were observed. At PND 31, few group differences were detected in absolute and relative brain volumes, brain water diffusivity outcomes, or behavioral parameters using the novel object recognition task. Serum lipoprotein was higher in pigs receiving diets with added dietary bMFGM compared with the CONT group. Serum cholesterol and high-density lipoprotein significantly higher (all P < 0.05) in the MFGM-2.5 compared with the CONT group. However, cholesterol concentrations within the brain prefrontal cortex and hippocampus did not differ among dietary groups.Conclusion: In this pig model, dietary supplementation with bMFGM was well-tolerated and supported growth and dietary intake similar to the control formula. Added dietary bMFGM was associated with increased serum lipoprotein, but no group differences in early brain cholesterol concentrations, macrostructure, microstructure, or recognition memory pigs at 31 days of age. Further examination of longitudinal brain development and myelination in the pig, particularly at later ages/maturation, is warranted.

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Early life diet containing prebiotics and bioactive whey protein fractions increased dendritic spine density of rat hippocampal neurons

Cited by 19 publications

References 36 publications

PDE4D regulates Spine Plasticity and Memory in the Retrosplenial Cortex

PDE4D regulates Spine Plasticity and Memory in the Retrosplenial Cortex

Early life diets with prebiotics and bioactive milk fractions attenuate the impact of stress on learned helplessness behaviours and alter gene expression within neural circuits important for stress resistance

Evaluation of Dietary Bovine Milk Fat Globule Membrane Supplementation on Growth, Serum Cholesterol and Lipoproteins, and Neurodevelopment in the Young Pig

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