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Modulation of Serotonergic Stress Neurocircuitry by Dietary Prebiotics and Lactoferrin
Author(s) -
Chichlowski Maciej,
Mika Agnieszka,
Berg Brian,
Fleshner Monika
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.691.34
Subject(s) - endocrinology , dorsal raphe nucleus , medicine , locus coeruleus , serotonergic , corticosterone , in situ hybridization , biology , raphe nuclei , serotonin , chemistry , central nervous system , messenger rna , hormone , biochemistry , receptor , gene
Early life nutrition impacts many aspects of physiology and behavior. In our previous studies, rats fed prebiotic diets exhibited reduced anxiety and depressive‐like behavior produced by uncontrollable stress. The current study tested if 4 weeks of early life diets that vary in prebiotics (galactooligosaccharide, GOS + polydextrose, PDX) and globular glycoprotein (lactoferrin, LAC) would change the activation ( cfos mRNA expression) of brain regions associated with the central stress response. The brain regions examined were the dorsal raphe nucleus (DRN), the locus coeruleus (LC), and nucleus of the solitary tract (NTS). Male F344 rats (p24) were pair‐housed in a barrier facility and fed experimental or control diet. The diet formulations were as follows: Control diet; LAC; GOS + PDX; and GOS + PDX+ LAC. After 4 weeks, rats were exposed to 100, 1.6mA, 5‐s, unpredictable, inescapable tail shocks (100 IS) or remained in their home cages. Immediately after stressor termination, rats were rapidly decapitated and blood, brain and peripheral tissues were collected. Brains were processed for assessment of mRNA expression using in situ hybridization. Expected increases in food intake and body weight were observed over time but not affected by diets. Stressor exposure reduced spleen wt (a proxy for sympathetic nervous system activation), corticosterone and glucose; and diet did not impact these responses. Stress increased cfos mRNA expression in all regions of the DRN. Mice fed diets including GOS+PDX exhibited reduced stress‐evoked cfos mRNA expression in the rostral DRN (dorsal, ventral and lateral regions); whereas GOS+PDX, LAC and LAC+GOS+PDX diets attenuated stress‐evoked cfos mRNA expression in the ventral mid and lateral mid regions of the DRN. In contrast, stress robustly increased cfos mRNA expression in the LC and NTS and diet did not modulate this effect. We further tested if diet would impact the effect of stress on 5‐HT 1a receptor mRNA. The 5‐HT 1a receptor is a serotonergic inhibitory autoreceptor that regulates DRN activation; prior work has demonstrated that enhanced stress resistance is associated with increased gene expression for the 5‐HT 1a receptor. Stress decreased 5‐HT 1a receptor mRNA in the rostral and mid DRN and this decrease was attenuated in all experimental diets (GOS+PDX, LAC and LAC+GOS+PDX) within the rostral DRN, whereas within the mid DRN, this decrease was only attenuated by diets containing GOS+PDX. These data suggest early life diets that contain prebiotics and/or lactoferrin may selectively modulate the serotonergic stress neurocircuitry in a manner that supports behavioral stress resistance. Support or Funding Information Supported by Mead Johnson Nutrition.