scholarly journals Maternal feeding patterns affect the offspring’s brain: focus on serotonin 5-HT2C and 5-HT2A receptors

Author(s):  
Kinga Gawlińska ◽  
Dawid Gawliński ◽  
Małgorzata Filip ◽  
Edmund Przegaliński

Abstract Background Recent studies have shown a relationship between the composition of the maternal diet and acquiring a risk of mental illnesses through changes in the offspring’s brain. This study assessed the role of a modified maternal diet on the levels of serotonin (5-HT)2C and 5-HT2A receptors in the offspring brain. Methods Wistar rat dams during gestation and lactation were maintained either on a standard (SD) or special diets: high-fat (HFD), high-carbohydrate (rich in sucrose, HCD) or mixed (MD). Offspring were weaned to SD after lactation, and at postnatal days (PNDs) 28 and 63 changes in the 5-HT2C and 5-HT2A receptor levels were evaluated in their prefrontal cortex (PFCx), nucleus accumbens (NAc), dorsal striatum (DSTR) and hippocampus (HIP). Results Maternal HFD reduced the expression of 5-HT2C receptors in male rats at PND 28 in the PFCx, NAc, and DSTR but increased it at PND 63 in male animals in the NAc and DSTR. HCD induced a decrease in the expression of 5-HT2C receptors in male offspring at PND 28 but increased it in female rats at PND 63 in the PFCx. MD reduced 5-HT2C receptor expression in males at PND 28 in the PFCx and increased it in male and female offspring at PND 28 in the HIP. Moreover, maternal HFD reduced 5-HT2A receptor levels within the PFCx in adolescent male offspring. Conclusion Our findings indicate that a modified maternal diet induces age- and sex-specific adaptive changes mainly in 5-HT2C receptors, which may contribute to disturbances in the offspring brain. Graphic abstract

2007 ◽  
Vol 292 (5) ◽  
pp. R1810-R1818 ◽  
Author(s):  
Claire J. Stocker ◽  
Ed Wargent ◽  
Jacqueline O'Dowd ◽  
Claire Cornick ◽  
John R. Speakman ◽  
...  

Absence of leptin is known to disrupt the development of energy balance regulatory mechanisms. We investigated whether administration of leptin to normally nourished rats affects energy balance in their offspring. Leptin (2 mg·kg−1·day−1) was administered from day 14 of pregnancy and throughout lactation. Male and female offspring were fed either on chow or on high-fat diets that elicited similar levels of obesity in the sexes from 6 wk to 15 mo of age. Treatment of the dams with leptin prevented diet-induced increases in the rate of weight gain, retroperitoneal fat pad weight, area under the intraperitoneal glucose tolerance curve, and fasting plasma insulin concentration in female offspring. In the male offspring, the diet-induced increase in weight gain was prevented and increased fat pad weight was reduced. Energy intake per rat was higher in response to the obesogenic diet in male offspring of saline-treated but not leptin-treated dams. A similar trend was seen in 3-mo-old female offspring. Energy expenditure at 3 mo of age was higher for a given body weight in female offspring of leptin-treated compared with saline-treated dams when these animals were fed on the obesogenic diet. A similar trend was seen for male rats fed on the obesogenic diet. Thus leptin levels during pregnancy and lactation can affect the development of energy balance regulatory systems in their offspring.


2018 ◽  
Vol 96 (8) ◽  
pp. 882-887 ◽  
Author(s):  
Chao Yin ◽  
Guofu Wang ◽  
Shixing Gao ◽  
Yanping Huang ◽  
Ruqian Zhao ◽  
...  

This study evaluated the effect of maternal restraint stress during the gestation period on behaviors, biochemical parameters, and antioxidant capacities of offspring rats (Rattus norvegicus (Berkenhout,1769)) at weaning age. Behaviors, plasma biochemical indices, and antioxidant ability of the liver, soleus muscle, and gastrocnemius muscle of mother and (or) offspring rats were analyzed. Significant increases were found in the immobility and swinging behavior frequencies of offspring male rats; no difference was found in behaviors of female rats. The antioxidant indices including superoxide dismutase, nitric oxide synthase, and total antioxidant capacity in the soleus muscle of offspring male rats were significantly decreased in the restraint group. Female offspring rats showed significant lower glutathione and higher malondialdehyde levels in the gastrocnemius muscle and liver, respectively. No difference was found in the productive performance and plasma biochemical indices of maternal rats, nor in the biochemical parameters of the two groups of weaning rats. The results suggested that maternal chronic stresses negatively affected the behaviors and antioxidant abilities of offspring rats, and that these effects possibly have a greater impact on offspring male rats than on female rats.


Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1462
Author(s):  
Dawid Gawliński ◽  
Kinga Gawlińska ◽  
Małgorzata Frankowska ◽  
Małgorzata Filip

Recent studies have emphasized the role of the maternal diet in the development of mental disorders in offspring. Substance use disorder is a major global health and economic burden. Therefore, the search for predisposing factors for the development of this disease can contribute to reducing the health and social damage associated with addiction. In this study, we focused on the impact of the maternal diet on changes in melanocortin-4 (MC-4) receptors as well as on behavioral changes related to cocaine addiction. Rat dams consumed a high-fat diet (HFD), high-sugar diet (HSD, rich in sucrose), or mixed diet (MD) during pregnancy and lactation. Using an intravenous cocaine self-administration model, the susceptibility of female offspring to cocaine reward and cocaine-seeking propensities was evaluated. In addition, the level of MC-4 receptors in the rat brain structures related to cocaine reward and relapse was assessed. Modified maternal diets did not affect cocaine self-administration in offspring. However, the maternal HSD enhanced cocaine-seeking behavior in female offspring. In addition, we observed that the maternal HSD and MD led to increased expression of MC-4 receptors in the nucleus accumbens, while increased MC-4 receptor levels in the dorsal striatum were observed after exposure to the maternal HSD and HFD. Taken together, it can be concluded that a maternal HSD is an important factor that triggers cocaine-seeking behavior in female offspring and the expression of MC-4 receptors.


2005 ◽  
Vol 289 (4) ◽  
pp. R1131-R1136 ◽  
Author(s):  
Lori L. Woods ◽  
Julie R. Ingelfinger ◽  
Ruth Rasch

Modest maternal dietary protein restriction in the rat leads to hypertension in adult male offspring. The purpose of this study was to determine whether female rats are resistant to developing the increased blood pressure seen in male rats after maternal protein restriction. Pregnant rats were fed a normal protein (19%, NP) or low-protein (8.5%, LP) diet throughout gestation. Renal renin protein and ANG II levels were reduced by 50–65% in male LP compared with NP pups, but were not suppressed in female LP compared with female NP. Mean arterial pressure in conscious, chronically instrumented adult female offspring (22 wk) was not different in LP (LP: 120 ± 3 mmHg vs. NP: 121 ± 2 mmHg), and glomerular filtration rate was also not different in LP vs. NP. The number of glomeruli per kidney was similar in adult LP and NP female offspring (LP: 26,050 ± 2,071 vs. NP: 26,248 ± 1,292, NP), and individual glomerular volume was also not different (LP: 0.92 ± 0.11 106μm3, LP vs. NP: 1.07 ± 0.11 106μm3); the total volume of all glomeruli per kidney was also not significantly different. Thus female rats are relatively resistant to the programming for adult hypertension by perinatal protein restriction that we have described in males. This resistance may be due to the fact that modest maternal protein restriction does not reduce the number of glomeruli with which females are endowed as it does in males. The intrarenal renin-angiotensin system during development may play a key role in this protective effect of female gender.


1989 ◽  
Vol 3 (3) ◽  
pp. 229-237 ◽  
Author(s):  
S. Tejura ◽  
G. R. Rodgers ◽  
M. H. Dunion ◽  
M. A. Parsons ◽  
J. C. E. Underwood ◽  
...  

ABSTRACT The results of this study confirm our previous report of increased androgen receptor expression in livers of female SUAH Wistar rats during development of liver tumours induced by diethylnitrosamine (DENA). In adult female rats not treated with DENA, removal of the ovary increased liver androgen receptor levels but testosterone did not further enhance the androgen receptor status of ovariectomized rats. In normal adult males the testis and/or testosterone maintained high levels of androgen receptors but oestrogen reduced them in castrated rats. Oestrogen receptor levels were not significantly changed in either males or females by gonadectomy. Treatment of female rats with DENA for 10 and 16 weeks increased liver androgen receptors but oestrogen receptors were only reduced by 16 weeks of DENA treatment, whether the rats were intact or ovariectomized. Concentrations of liver androgen receptors were increased in intact and castrated male rats by 10 and 16 weeks of DENA treatment, an increase not seen in the previous experiments. Oestrogen appeared to inhibit both the increases in liver androgen receptor expression and liver tumour development in rats treated with the weakly carcinogenic dose of 10 weeks of DENA. However, the full carcinogenic dose of 16 weeks of DENA increased liver androgen receptors and decreased oestrogen receptors in female rats regardless of sex-steroid status. Development of malignant hepatocellular carcinoma (HCC) was associated with both an increase in liver androgen receptors and a decrease in oestrogen receptors. Maintenance of relatively high levels of liver oestrogen receptors appeared to protect the liver against development of HCC.


2014 ◽  
Vol 112 (12) ◽  
pp. 1933-1937 ◽  
Author(s):  
Thomas M. Wright ◽  
Madeleine V. King ◽  
William G. Davey ◽  
Simon C. Langley-Evans ◽  
Jörg-Peter W. Voigt

There is increasing evidence that hyperenergetic diets have an impact on memory in rodents. However, it is largely unknown how diets, such as a cafeteria diet (CD), that mimic a Western-type diet act on learning and memory, in particular when fed during early stages of development. Here, we fed lactating dams a CD and exposed both male and female offspring to a novel object discrimination (NOD) task, a two-trial test of recognition memory in which rats exposed to two identical objects during a training/familiarisation trial can discriminate a novel from a familiar object during the subsequent choice trial. The choice trial was performed following inter-trial interval (ITI) delays of up to 4 h. Maternal diet did not have an impact on exploration of the objects by either sex during the familiarisation trial. Control males discriminated the novel from the familiar object, indicating intact memory with an ITI of 1 h, but not 2 or 4 h. The CD delayed this natural forgetting in male rats such that discrimination was also evident after a 2 h ITI. In contrast, control females exhibited discrimination following both 1 and 2 h ITI, but the CD impaired performance. In summary, the present study shows that maternal exposure to the CD programmes NOD in the adult. In better-performing females, dietary programming interferes with NOD, whereas NOD was improved in males after lactational CD feeding.


Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 89
Author(s):  
Soniya Xavier ◽  
Jasmine Gili ◽  
Peter McGowan ◽  
Simin Younesi ◽  
Paul F. A. Wright ◽  
...  

Maternal diet is critical for offspring development and long-term health. Here we investigated the effects of a poor maternal diet pre-conception and during pregnancy on metabolic outcomes and the developing hypothalamus in male and female offspring at birth. We hypothesised that offspring born to dams fed a diet high in fat and sugar (HFSD) peri-pregnancy will have disrupted metabolic outcomes. We also determined if these HFSD-related effects could be reversed by a shift to a healthier diet post-conception, in particular to a diet high in omega-3 polyunsaturated fatty acids (ω3 PUFAs), since ω3 PUFAs are considered essential for normal neurodevelopment. Unexpectedly, our data show that there are minimal negative effects of maternal HFSD on newborn pups. On the other hand, consumption of an ω3-replete diet during pregnancy altered several developmental parameters. As such, pups born to high-ω3-fed dams weighed less for their length, had reduced circulating leptin, and also displayed sex-specific disruption in the expression of hypothalamic neuropeptides. Collectively, our study shows that maternal intake of a diet rich in ω3 PUFAs during pregnancy may be detrimental for some metabolic developmental outcomes in the offspring. These data indicate the importance of a balanced dietary intake in pregnancy and highlight the need for further research into the impact of maternal ω3 intake on offspring development and long-term health.


2010 ◽  
Vol 299 (5) ◽  
pp. F1164-F1170 ◽  
Author(s):  
Xiaoyan Wang ◽  
Fengmin Li ◽  
Pedro A. Jose ◽  
Carolyn M. Ecelbarger

Dopamine produced by renal proximal tubules increases sodium excretion via a decrease in renal sodium reabsorption. Dopamine natriuresis is impaired in obese Zucker rats; however, the mechanism is not fully understood. To test the hypothesis that renal expression of one or more of the subtypes are altered in these rats, we measured whole kidney protein levels by immunoblotting of D1-like (D1R and D5R) and D2-like (D2R, D3R, and D4R) dopamine receptors in both male and female obese and lean Zucker rats. In obese males on 1% NaCl diet, D1R, D2R, D4R, and D5R were decreased, while D3R was increased, relative to lean rats. Under a 4% NaCl diet, D2R and D3R levels in obese rats were restored to lean levels. 4% NaCl diet reduced D5R in both body types, relative to 1% NaCl diet. Female rats had higher expression of D1R and D3R than did male; however, the sex difference for D1R was markedly blunted in obese rats. In obese rats, dietary candesartan (angiotensin II type 1 receptor blocker) normalized downregulated D1R and D2R, but either decreased (D3R), did not affect (D4R), or further downregulated (D5R) the other subtypes. Candesartan also decreased D4R in lean rats. In summary, reduced renal protein levels of D1R, D2R, D4R, and D5R in obese Zucker rats could induce salt sensitivity and elevate blood pressure. Increased angiotensin II type 1 receptor activity may be mechanistically involved in the decreased expression of D1R and D2R in obese rats. Finally, reduced D1R and D3R in male rats may contribute to sex differences in blood pressure.


2013 ◽  
Vol 305 (8) ◽  
pp. F1099-F1104 ◽  
Author(s):  
Chunhua Jin ◽  
Joshua S. Speed ◽  
Kelly A. Hyndman ◽  
Paul M. O'Connor ◽  
David M. Pollock

The inner medullary collecting duct (IMCD) is the nephron segment with the highest production of endothelin-1 (ET-1) and the greatest expression of ET-1 receptors that function to adjust Na+ and water balance. We have reported that male rats have reduced natriuresis in response to direct intramedullary infusion of ET-1 compared with female rats. Our aim was to determine whether alterations of ET-1 receptor expression and downstream intracellular Ca2+ signaling within the IMCD could account for these sex differences. IMCDs from male and female rats were isolated for radioligand binding or microdissected for intracellular Ca2+ ([Ca2+]i) measurement by fluorescence imaging of fura-2 AM. IMCD from male and female rats had similar ETB expression (655 ± 201 vs. 567 ± 39 fmol/mg protein, respectively), whereas male rats had significantly higher ETA expression (436 ± 162 vs. 47 ± 29 fmol/mg protein, respectively; P < 0.05). The [Ca2+]i response to ET-1 was significantly greater in IMCDs from male compared with female rats (288 ± 52 vs. 118 ± 32 AUC, nM × 3 min, respectively; P < 0.05). In IMCDs from male rats, the [Ca2+]i response to ET-1 was significantly blunted by the ETA antagonist BQ-123 but not by the ETB antagonist BQ-788 (control: 137 ± 27; BQ-123: 53 ± 11; BQ-788: 84 ± 25 AUC, nM × 3 min; P < 0.05), consistent with greater ETA receptor function in male rats. These data demonstrate a sex difference in ETA receptor expression that results in differences in ET-1 Ca2+ signaling in IMCD. Since activation of ETA receptors is thought to oppose ETB receptor activation, enhanced ETA function in male rats could limit the natriuretic effects of ETB receptor activation.


2014 ◽  
Vol 112 (9) ◽  
pp. 2275-2282 ◽  
Author(s):  
Hayes Wong ◽  
Xu-Dong Dong ◽  
Brian E. Cairns

Intramuscular injection of nerve growth factor (NGF) into rat masseter muscle induces a local mechanical sensitization that is greater in female than in male rats. The duration of NGF-induced sensitization in male and female rats was associated with an increase in peripheral N-methyl-d-aspartate (NMDA) receptor expression by masseter muscle afferent fibers that began 3 days postinjection. Here, we investigated the functional consequences of increased NMDA expression on the response properties of masseter muscle mechanoreceptors. In vivo extracellular single-unit electrophysiological recordings of trigeminal ganglion neurons innervating the masseter muscle were performed in anesthetized rats 3 days after NGF injection (25 μg/ml, 10 μl) into the masseter muscle. Mechanical activation threshold was assessed before and after intramuscular injection of NMDA. NMDA injection induced mechanical sensitization in both sexes that was increased significantly following NGF injection in the male rats but not in the female rats. However, in female but not male rats, further examination found that preadministration of NGF induced a greater sensitization in slow Aδ-fibers (2–7 m/s) than fast Aδ-fibers (7–12 m/s). This suggests that preadministration of NGF had a different effect on slowly conducting mechanoreceptors in the female rats compared with the male rats. Although previous studies have found an association between estrogenic tone and NMDA activity, no correlation was observed between NMDA-evoked mechanical sensitization and plasma estrogen level. This study suggests NGF alters NMDA-induced mechanical sensitization in the peripheral endings of masseter mechanoreceptors in a sexually dimorphic manner.


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