Adult emotionality and neural plasticity as a function of adolescent nutrient supplementation in male rats

Abstract

The present study explored the effects of supplementing male rats with either choline, omega-3 fatty acids, or phytoestrogens, from weaning into early adulthood, on emotionality and hippocampal plasticity. Because of the neuroprotective properties of these nutrients, we hypothesized that they would positively affect both behavior and hippocampal function when compared to non-supplemented control rats. To test this hypothesis, male Sprague Dawley rats were assigned to one of four nutrient conditions after weaning: 1) control (normal rat chow); 2) choline (supplemented in drinking water); 3) omega 3 fatty acids (daily oral supplements); or 4) phytoestrogens (supplemented in chow). After 4 weeks on their respective diets, a subset of rats began 3 weeks of behavioral testing, while the remaining behaviorally naïve rats were sacrificed after 6 weeks on the diets to assess numbers of adult-born hippocampal neurons using the immature neuron marker, doublecortin. The results revealed that choline supplementation affected emotional functioning; compared to rats in other diet conditions, rats in this group were less anxious in an open field and after exposure to predator odor and showed less behavioral despair after forced swimming. Similar behavioral findings were evident following supplementation with omega-3 fatty acids and phytoestrogens supplementation, though not on all tests and not to the same magnitude. Histological findings followed a pattern consistent with the behavioral findings: choline supplementation, followed by omega-3 fatty acid supplementation, but not phytoestrogen supplementation, significantly increased the numbers of new-born hippocampal neurons. Choline and omega −3 fatty acids have similar biological functions—affecting cell membranes, growth factor levels, and epigenetically altering gene transcription. Thus, the present findings suggest that targeting nutrients with these effects may be a viable strategy to combat adult psychopathologies.

Prenatal choline supplementation attenuates MK-801-induced deficits in memory, motor function, and hippocampal plasticity in adult male rats

“…Past research indicates that dietary supplementation with choline increases cell proliferation and hippocampal neurogenesis (Glenn et al, 2007; 2008; McCall et al, 2015) and accordingly the prenatal choline supplementation of the current study was expected to combat reductions in these markers caused by MK-801 in adult rats. In accordance with this hypothesis, the current investigation revealed that choline-supplemented rats given MK-801 had significantly more newly-divided cells in the dentate gyrus compared to standard-fed rats given MK-801.…”

“…Though dietary choline supplementation is protective throughout the lifespan (Zeisel, 2006), a greater protective capacity is exhibited when the supplementation occurs in early development as opposed to in adolescence or in adulthood (Meck et al, 2008; Wong-Goodrich et al, 2008a; Glenn et al, 2012). Early life choline supplementation in rats, either prenatally, neonatally, or post-weaning, exerts neuroprotection in a wide array of disease models, including epilepsy (Wong-Goodrich et al, 2008b; 2011), Down syndrome (Strupp et al, 2016), Rett syndrome (Nag and Berger-Sweeney et al, 2007; Nag et al, 2009), fetal alcohol syndrome (Thomas et al, 2003; 2007; Schneider and Thomas, 2016), depression (Glenn et al, 2012; McCall et al, 2015: Schulz et al, 2014), and schizophrenia (Corriveau and Glenn, 2012; Stevens et al, 2008; 2014). In addition to these disease models, early life choline supplementation also attenuates the effects of exposure to the neurotoxin, MK-801 (Guo-Ross et al, 2002; 2003).…”

“…Three days following this dose, adult hippocampal neurogenesis and cell proliferation was assessed. Prenatal choline supplementation increases adult hippocampal neurogenesis (Glenn et al, 2007; McCall et al, 2015) and cell proliferation (Glenn et al, 2007; 2008), but there is not a clear understanding of the role of MK-801 in this process: mixed results indicate that MK-801 both increases (Nacher et al, 2003) and decreases neurogenesis (Arvidsson et al, 2001). Therefore, the present research seeks to clarify this inconsistency as well as determine the interactive effects of MK-801 and prenatal choline diet.…”

New method to induce mild traumatic brain injury in rodents produces differential outcomes in female and male Sprague Dawley rats

“…Post-fixed brains were sectioned through the rostral-caudal extent of the hippocampal formation on a vibratome with every 4 th 40-µm section retained for doublecortin (DCX) immunohistochemistry, which was conducted as previously described (Glenn et al, 2007; McCall et al, 2015). Briefly, free floating sections were rinsed in Tris-buffered saline (TBS; pH 7.3) and treated with 0.6% hydrogen peroxide for 30 minutes followed by incubation in 0.1% Triton X-100 (TTX; Sigma-Aldrich Corp., St. Louis, MO) and 3% normal horse serum (NHS; Vector Laboratories, Burlingame, CA) at room temperature to reduce non-specific staining.…”

“…Using the same sections, estimates of the volume of dentate gyrus sampled in each rat was obtained based on the boundaries of the contour tracings and final estimates of numbers of DCX-labeled neurons are shown as numbers per volume of dentate gyrus. This method minimizes the contribution of differences in the contour region traced or region size among rats or groups, particularly occurring as a result of brain size differences between females and males (McCall et al, 2015). …”