Abstract
The medial prefrontal cortex (mPFC) is a key area for the regulation of numerous brain functions including stress response and cognitive processes. This brain area is also particularly affected by adversity during early life. Using an animal model in rats, we recently demonstrated that maternal exposure to a high-fat diet (HFD) prevents maternal separation (MS)-induced gene expression alterations in the developing PFC and attenuates several long-term deleterious behavioral effects of MS. In the present study, we ask whether maternal HFD could protect mPFC neurons of pups exposed to early life stress by examining dendritic morphology and spine density in juvenile [postnatal day (PND) 21] and adult rats submitted to MS. Dams were fed either a control or an HFD throughout gestation and lactation, and pups were submitted to MS from PND2 to PND14. We report that maternal HFD prevents MS-induced spine loss at PND21 and dendritic atrophy at adulthood. Furthermore, we show in adult MS rats that PFC-dependent memory extinction deficits are prevented by maternal HFD. Finally, perinatal HFD exposure reverses gut leakiness following stress in pups and seems to exert an anti-stress effect in dams. Overall, our work demonstrates that maternal HFD affects the developing brain and suggests that nutrition, possibly through gut–brain interactions, could modulate mPFC sensitivity to early stress.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ait-Belgnaoui A, Durand H, Cartier C et al (2012) Prevention of gut leakiness by a probiotic treatment leads to attenuated HPA response to an acute psychological stress in rats. Psychoneuroendocrinology 37:1885–1895. doi:10.1016/j.psyneuen.2012.03.024
Awad W, Ferreira G, Maroun M (2015) Dissociation of the role of infralimbic cortex in learning and consolidation of extinction of recent and remote aversion memory. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol 40:2566–2575. doi:10.1038/npp.2015.103
Baker KD, Reichelt AC (2016) Impaired fear extinction retention and increased anxiety-like behaviours induced by limited daily access to a high-fat/high-sugar diet in male rats: implications for diet-induced prefrontal cortex dysregulation. Neurobiol Learn Mem 136:127–138. doi:10.1016/j.nlm.2016.10.002
Baudin A, Blot K, Verney C et al (2012) Maternal deprivation induces deficits in temporal memory and cognitive flexibility and exaggerates synaptic plasticity in the rat medial prefrontal cortex. Neurobiol Learn Mem 98:207–214. doi:10.1016/j.nlm.2012.08.004
Belzung C, Le Pape G (1994) Comparison of different behavioral test situations used in psychopharmacology for measurement of anxiety. Physiol Behav 56:623–628. doi:10.1016/0031-9384(94)90311-5
Blaze J, Roth TL (2013) Exposure to caregiver maltreatment alters expression levels of epigenetic regulators in the medial prefrontal cortex. Int J Dev Neurosci 31:804–810. doi:10.1016/j.ijdevneu.2013.10.001
Bocarsly ME, Fasolino M, Kane GA et al (2015) Obesity diminishes synaptic markers, alters microglial morphology, and impairs cognitive function. Proc Natl Acad Sci USA 112:15731–15736. doi:10.1073/pnas.1511593112
Bock J, Gruss M, Becker S, Braun K (2005) Experience-induced changes of dendritic spine densities in the prefrontal and sensory cortex: correlation with developmental time windows. Cereb Cortex 15:802–808. doi:10.1093/cercor/bhh181
Bourre JM, Pascal G, Durand G et al (1984) Alterations in the fatty acid composition of rat brain cells (neurons, astrocytes, and oligodendrocytes) and of subcellular fractions (myelin and synaptosomes) induced by a diet devoid of n-3 fatty acids. J Neurochem 43:342–348. doi:10.1111/j.1471-4159.1984.tb00906.x
Cerqueira JJ, Taipa R, Uylings HBM et al (2007) Specific configuration of dendritic degeneration in pyramidal neurons of the medial prefrontal cortex induced by differing corticosteroid regimens. Cereb Cortex 17:1998–2006. doi:10.1093/cercor/bhl108
Champagne DL, Bagot RC, van Hasselt F et al (2008) Maternal care and hippocampal plasticity: evidence for experience-dependent structural plasticity, altered synaptic functioning, and differential responsiveness to glucocorticoids and stress. J Neurosci 28:6037–6045. doi:10.1523/JNEUROSCI.0526-08.2008
Chocyk A, Bobula B, Dudys D et al (2013) Early-life stress affects the structural and functional plasticity of the medial prefrontal cortex in adolescent rats. Eur J Neurosci 38:2089–2107. doi:10.1111/ejn.12208
Cook SC, Wellman CL (2004) Chronic stress alters dendritic morphology in rat medial prefrontal cortex. J Neurobiol 60:236–248. doi:10.1002/neu.20025
Cubelos B, Briz CG, Esteban-Ortega GM, Nieto M (2015) Cux1 and Cux2 selectively target basal and apical dendritic compartments of layer II–III cortical neurons. Dev Neurobiol 75:163–172. doi:10.1002/dneu.22215
Dallman MF, Pecoraro N, Akana SF et al (2003) Chronic stress and obesity: a new view of “comfort food”. Proc Natl Acad Sci USA 100:11696–11701. doi:10.1073/pnas.1934666100
de Haan JJ, Thuijls G, Lubbers T, Hadfoune M, Reisinger K, Heineman E, Greve JW, Buurman WA (2010) Protection against early intestinal compromise by lipid-rich enteral nutrition through cholecystokinin receptors. Crit Care Med 38:1592–1597. doi:10.1097/CCM.0b013e3181e2cd4d
De Palma G, Blennerhassett P, Lu J et al (2015) Microbiota and host determinants of behavioural phenotype in maternally separated mice. Nat Commun 6:7735. doi:10.1038/ncomms8735
Del Rio D, Cano V, Martín-Ramos M et al (2015) Involvement of the dorsomedial prefrontal cortex in high-fat food conditioning in adolescent mice. Behav Brain Res 283:227–232. doi:10.1016/j.bbr.2015.01.039
Deroulers C, Ameisen D, Badoual M et al (2013) Analyzing huge pathology images with open source software. Diagn Pathol 8:92. doi:10.1186/1746-1596-8-92
Dias-Ferreira E, Sousa JC, Melo I et al (2009) Chronic stress causes frontostriatal reorganization and affects decision-making. Science 325:621–625. doi:10.1126/science.1171203
Dingess PM, Darling RA, Kurt Dolence E et al (2017) Exposure to a diet high in fat attenuates dendritic spine density in the medial prefrontal cortex. Brain Struct Funct 222:1077–1085. doi:10.1007/s00429-016-1208-y
Euston DR, Gruber AJ, McNaughton BL (2012) The role of medial prefrontal cortex in memory and decision making. Neuron 76:1057–1070. doi:10.1016/j.neuron.2012.12.002
Farrell MR, Holland FH, Shansky RM, Brenhouse HC (2016) Sex-specific effects of early life stress on social interaction and prefrontal cortex dendritic morphology in young rats. Behav Brain Res 310:119–125. doi:10.1016/j.bbr.2016.05.009
Finger BC, Dinan TG, Cryan JF (2011) High-fat diet selectively protects against the effects of chronic social stress in the mouse. Neuroscience 192:351–360. doi:10.1016/j.neuroscience.2011.06.072
Franklin TB, Saab BJ, Mansuy IM (2012) Neural mechanisms of stress resilience and vulnerability. Neuron 75:747–761. doi:10.1016/j.neuron.2012.08.016
García-Ródenas CL, Bergonzelli GE, Nutten S et al (2006) Nutritional approach to restore impaired intestinal barrier function and growth after neonatal stress in rats. J Pediatr Gastroenterol Nutr 43:16–24. doi:10.1097/01.mpg.0000226376.95623.9f
Gareau MG, Jury J, Yang PC et al (2006) Neonatal maternal separation causes colonic dysfunction in rat pups including impaired host resistance. Pediatr Res 59:83–88. doi:10.1203/01.pdr.0000190577.62426.45
Garrett JE, Wellman CL (2009) Chronic stress effects on dendritic morphology in medial prefrontal cortex: sex differences and estrogen dependence. Neuroscience 162:195–207. doi:10.1016/j.neuroscience.2009.04.057
Goodfellow NM, Benekareddy M, Vaidya VA, Lambe EK (2009) Layer II/III of the prefrontal cortex: inhibition by the serotonin 5-HT1A receptor in development and stress. J Neurosci 29:10094–10103. doi:10.1523/JNEUROSCI.1960-09.2009
Hatanaka Y, Wada K, Kabuta T (2016) Maternal high-fat diet leads to persistent synaptic instability in mouse offspring via oxidative stress during lactation. Neurochem Int 97:99–108. doi:10.1016/j.neuint.2016.03.008
Janthakhin Y, Rincel M, Costa A-M et al (2017) Maternal high-fat diet leads to hippocampal and amygdala dendritic remodeling in adult male offspring. Psychoneuroendocrinology 83:49–57. doi:10.1016/j.psyneuen.2017.05.003
Kelly JR, Kennedy PJ, Cryan JF et al (2015) Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders. Front Cell Neurosci 9:392. doi:10.3389/fncel.2015.00392
Kolb B, Mychasiuk R, Muhammad A et al (2012) Experience and the developing prefrontal cortex. Proc Natl Acad Sci USA 109(Suppl 2):17186–17193. doi:10.1073/pnas.1121251109
Krolow R, Noschang CG, Arcego D et al (2010) Consumption of a palatable diet by chronically stressed rats prevents effects on anxiety-like behavior but increases oxidative stress in a sex-specific manner. Appetite 55:108–116. doi:10.1016/j.appet.2010.03.013
Labouesse MA, Lassalle O, Richetto J et al (2017) Hypervulnerability of the adolescent prefrontal cortex to nutritional stress via reelin deficiency. Mol Psychiatry 22:961–971. doi:10.1038/mp.2016.193
Lam YY, Ha CW, Hoffmann JM, Oscarsson J, Dinudom A, Mather TJ, Cook DI, Hunt NH, Caterson ID, Holmes AJ, Storlien LH (2015) Effects of dietary fat profile on gut permeability and microbiota and their relationships with metabolic changes in mice. Obesity (Silver Spring) 23:1429–1439. doi:10.1002/oby.21122
Larrieu T, Hilal ML, Hilal LM et al (2014) Nutritional omega-3 modulates neuronal morphology in the prefrontal cortex along with depression-related behaviour through corticosterone secretion. Transl Psychiatry 4:e437. doi:10.1038/tp.2014.77
Larrieu T, Hilal ML, De Smedt-Peyrusse V et al (2016) Nutritional omega-3 deficiency alters glucocorticoid receptor-signaling pathway and neuronal morphology in regionally distinct brain structures associated with emotional deficits. Neural Plast 2016:8574830. doi:10.1155/2016/8574830
Lépinay AL, Larrieu T, Joffre C et al (2015) Perinatal high-fat diet increases hippocampal vulnerability to the adverse effects of subsequent high-fat feeding. Psychoneuroendocrinology 53:82–93. doi:10.1016/j.psyneuen.2014.12.008
Li M, Xue X, Shao S et al (2013) Cognitive, emotional and neurochemical effects of repeated maternal separation in adolescent rats. Brain Res 1518:82–90. doi:10.1016/j.brainres.2013.04.026
Liston C, Miller MM, Goldwater DS et al (2006) Stress-induced alterations in prefrontal cortical dendritic morphology predict selective impairments in perceptual attentional set-shifting. J Neurosci 26:7870–7874. doi:10.1523/JNEUROSCI.1184-06.2006
Luczynski P, Whelan SO, O’Sullivan C et al (2016) Adult microbiota-deficient mice have distinct dendritic morphological changes: differential effects in the amygdala and hippocampus. Eur J Neurosci 44:2654–2666. doi:10.1111/ejn.13291
Maniam J, Morris MJ (2010a) Palatable cafeteria diet ameliorates anxiety and depression-like symptoms following an adverse early environment. Psychoneuroendocrinology 35:717–728. doi:10.1016/j.psyneuen.2009.10.013
Maniam J, Morris MJ (2010b) Long-term postpartum anxiety and depression-like behavior in mother rats subjected to maternal separation are ameliorated by palatable high fat diet. Behav Brain Res 208:72–79. doi:10.1016/j.bbr.2009.11.005
Maniam J, Antoniadis CP, Le V, Morris MJ (2016) A diet high in fat and sugar reverses anxiety-like behaviour induced by limited nesting in male rats: impacts on hippocampal markers. Psychoneuroendocrinology 68:202–209. doi:10.1016/j.psyneuen.2016.03.007
McEwen BS, Morrison JH (2013) The brain on stress: vulnerability and plasticity of the prefrontal cortex over the life course. Neuron 79:16–29. doi:10.1016/j.neuron.2013.06.028
Michelsen KA, van den Hove DL, Schmitz C et al (2007) Prenatal stress and subsequent exposure to chronic mild stress influence dendritic spine density and morphology in the rat medial prefrontal cortex. BMC Neurosci 8:107. doi:10.1186/1471-2202-8-107
Mogi K, Ishida Y, Nagasawa M, Kikusui T (2016) Early weaning impairs fear extinction and decreases brain-derived neurotrophic factor expression in the prefrontal cortex of adult male C57BL/6 mice. Dev Psychobiol 58:1034–1042. doi:10.1002/dev.21437
Monroy E, Hernández-Torres E, Flores G (2010) Maternal separation disrupts dendritic morphology of neurons in prefrontal cortex, hippocampus, and nucleus accumbens in male rat offspring. J Chem Neuroanat 40:93–101. doi:10.1016/j.jchemneu.2010.05.005
Moussaoui N, Braniste V, Ait-Belgnaoui A et al (2014) Changes in intestinal glucocorticoid sensitivity in early life shape the risk of epithelial barrier defect in maternal-deprived rats. PLoS One 9:e88382. doi:10.1371/journal.pone.0088382
Moya-Pérez A, Perez-Villalba A, Benítez-Páez A et al (2017) Bifidobacterium CECT 7765 modulates early stress-induced immune, neuroendocrine and behavioral alterations in mice. Brain Behav Immun 65:43–56. doi:10.1016/j.bbi.2017.05.011
Muhammad A, Kolb B (2011) Maternal separation altered behavior and neuronal spine density without influencing amphetamine sensitization. Behav Brain Res 223:7–16. doi:10.1016/j.bbr.2011.04.015
Muhammad A, Carroll C, Kolb B (2012) Stress during development alters dendritic morphology in the nucleus accumbens and prefrontal cortex. Neuroscience 216:103–109. doi:10.1016/j.neuroscience.2012.04.041
Paxinos G, Watson C (2014) The rat brain in stereotaxic coordinates, 7th edn. San Diego, Elsevier Academic press
Purcell RH, Sun B, Pass LL et al (2011) Maternal stress and high-fat diet effect on maternal behavior, milk composition, and pup ingestive behavior. Physiol Behav 104:474–479. doi:10.1016/j.physbeh.2011.05.012
Pusceddu MM, El Aidy S, Crispie F et al (2015) N-3 polyunsaturated fatty acids (PUFAs) reverse the impact of early-life stress on the gut microbiota. PLoS One 10:e0139721. doi:10.1371/journal.pone.0139721
Rincel M, Lépinay AL, Delage P et al (2016) Maternal high-fat diet prevents developmental programming by early-life stress. Transl Psychiatry 6:e966. doi:10.1038/tp.2016.235
Rodriguez A, Ehlenberger DB, Dickstein DL et al (2008) Automated three-dimensional detection and shape classification of dendritic spines from fluorescence microscopy images. PLoS One 3:e1997. doi:10.1371/journal.pone.0001997
Romaní-Pérez M, Lépinay AL, Alonso L et al (2017) Impact of perinatal exposure to high-fat diet and stress on responses to nutritional challenges, food-motivated behaviour and mesolimbic dopamine function. Int J Obes 41:502–509. doi:10.1038/ijo.2016.236
Romano-López A, Méndez-Díaz M, García FG et al (2016) Maternal separation and early stress cause long-lasting effects on dopaminergic and endocannabinergic systems and alters dendritic morphology in the nucleus accumbens and frontal cortex in rats. Dev Neurobiol 76:819–831. doi:10.1002/dneu.22361
Soztutar E, Colak E, Ulupinar E (2016) Gender- and anxiety level-dependent effects of perinatal stress exposure on medial prefrontal cortex. Exp Neurol 275(Pt 2):274–284. doi:10.1016/j.expneurol.2015.06.005
Spruston N (2008) Pyramidal neurons: dendritic structure and synaptic integration. Nat Rev Neurosci 9:206–221. doi:10.1038/nrn2286
Stranahan AM, Norman ED, Lee K et al (2008) Diet-induced insulin resistance impairs hippocampal synaptic plasticity and cognition in middle-aged rats. Hippocampus 18:1085–1088. doi:10.1002/hipo.20470
Thomas AW, Caporale N, Wu C, Wilbrecht L (2016) Early maternal separation impacts cognitive flexibility at the age of first independence in mice. Dev Cogn Neurosci 18:49–56. doi:10.1016/j.dcn.2015.09.005
Thompson JL, Drysdale M, Baimel C et al (2017) Obesity-induced structural and neuronal plasticity in the lateral orbitofrontal cortex. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol 42:1480–1490. doi:10.1038/npp.2016.284
Ulrich-Lai YM, Herman JP (2009) Neural regulation of endocrine and autonomic stress responses. Nat Rev Neurosci 10:397–409. doi:10.1038/nrn2647
Valladolid-Acebes I, Fole A, Martín M et al (2013) Spatial memory impairment and changes in hippocampal morphology are triggered by high-fat diets in adolescent mice. Is there a role of leptin? Neurobiol Learn Mem 106:18–25. doi:10.1016/j.nlm.2013.06.012
Van Eden CG, Uylings HB (1985) Cytoarchitectonic development of the prefrontal cortex in the rat. J Comp Neurol 241:253–267. doi:10.1002/cne.902410302
van Oers HJ, de Kloet ER, Whelan T, Levine S (1998) Maternal deprivation effect on the infant’s neural stress markers is reversed by tactile stimulation and feeding but not by suppressing corticosterone. J Neurosci 18:10171–10179
Wearne SL, Rodriguez A, Ehlenberger DB et al (2005) New techniques for imaging, digitization and analysis of three-dimensional neural morphology on multiple scales. Neuroscience 136:661–680
Yuste R, Bonhoeffer T (2004) Genesis of dendritic spines: insights from ultrastructural and imaging studies. Nat Rev Neurosci 5:24–34. doi:10.1038/nrn1300
Zhou X-Y, Li M, Li X et al (2016) Visceral hypersensitive rats share common dysbiosis features with irritable bowel syndrome patients. World J Gastroenterol 22:5211–5227. doi:10.3748/wjg.v22.i22.5211
Ziv NE, Smith SJ (1996) Evidence for a role of dendritic filopodia in synaptogenesis and spine formation. Neuron 17:91–102
Acknowledgements
This work was supported by the University of Bordeaux, Projet inter-régions Aquitaine et Midi-Pyrénées (Nutristress project), the AlimH department of the Institut National de la Recherche Agronomique (INRA), and by the French National Research Agency (IBISS project ANR-12-DSSA-0004). M. R. and A. L. L. were supported by a stipend of the French Ministry of Research and Higher Education. YJ was the recipient of a Ph.D. fellowship from the Ministry of Science and Technology of Thailand (2013–2016). The authors thank C. Poujol, S. Marais, and F. Cordelières of the Bordeaux Imaging Center for their help in the microscopy experiment, and M. Cadet and C. Testa for taking care of the rats.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflicts of interest.
Research involving human participants and/or animals
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures were in accordance with the ethical standards of the institution or practice at which the studies were conducted. This article does not contain any studies with human participants performed by any of the authors.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Rincel, M., Lépinay, A.L., Janthakhin, Y. et al. Maternal high-fat diet and early life stress differentially modulate spine density and dendritic morphology in the medial prefrontal cortex of juvenile and adult rats. Brain Struct Funct 223, 883–895 (2018). https://doi.org/10.1007/s00429-017-1526-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00429-017-1526-8