scholarly journals Folic acid, but not folate, regulates different stages of neurogenesis in the ventral hippocampus of adult female rats

2018 ◽  
Author(s):  
Wansu Qiu ◽  
Aarthi R. Gobinath ◽  
Yanhua Wen ◽  
Jehannine Austin ◽  
Liisa A.M. Galea
Keyword(s):  
Folic Acid ◽  
Adult Female ◽  
Ventral Hippocampus ◽  
Plasma Homocysteine ◽  
Hippocampal Neurogenesis ◽  
Female Rats ◽  
Sprague Dawley ◽  
Serum Corticosterone ◽  
Immature Neurons ◽  
Low Levels

ABSTRACTFolate is an important regulator of hippocampal neurogenesis, and in utero spinal cord development. Both high levels of folic acid and low levels of folate can be harmful to health, as low levels of folate have been linked to several diseases while high folic acid supplements can mask a vitamin B12 deficiency. Depressed patients exhibit folate deficiencies, lower levels of hippocampal neurogenesis, elevated levels of homocysteine, and elevated levels of the stress hormone, cortisol, which may be inter-related. Here, we are interested in whether different doses of natural folate or synthetic folic acid diets can influence neurogenesis in the hippocampus, levels of plasma homocysteine, and serum corticosterone in adult female rats. Adult female Sprague-Dawley rats underwent dietary interventions for 29 days. Animals were randomly assigned to six different dietary groups: folate deficient + succinylsulfathiazole (SST), low 5-methyltetrahydrofolate (5-MTHF), low 5-MTHF + (SST), high 5-MTHF + SST, low folic acid, and high folic acid. SST was added to a subset of the 5-MTHF diets to eliminate folic acid production in the gut. Before and after dietary treatment, blood samples were collected for corticosterone and homocysteine analysis, and brain tissue was collected for neurogenesis analysis. High folic acid and low 5-MTHF without SST increased the number of immature neurons (doublecortin-expressing cells) within the ventral hippocampus compared to folate deficient controls. Low 5-MTHF without SST significantly increased the number of immature neurons compared to low and high 5-MTHF + SST, indicating that SST interfered with elevations in neurogenesis. Low folic acid and high 5-MTHF+SST reduced plasma homocysteine levels compared to controls, but there was no significant effect of diet on serum corticosterone levels. Low folic acid and high 5-MTHF+SST reduced the number of mature new neurons in the ventral hippocampus (BrdU/NeuN-positive cells) compared to folate deficient controls. Overall, folic acid dose-dependently influenced neurogenesis, with low levels decreasing but high levels increasing, neurogenesis in the ventral hippocampus, suggesting this region, which is important for regulating stress, is particularly sensitive to folic acid in diets. Furthermore, the addition of SST negated the effects of 5-MTHF to increase neurogenesis in the ventral hippocampus.

scholarly journals Folic acid, but not folate, regulates different stages of neurogenesis in the ventral hippocampus of adult female rats

2019 ◽  
Vol 31 (10) ◽  
Author(s):  
Wansu Qiu ◽  
Aarthi R. Gobinath ◽  
Yanhua Wen ◽  
Jehannine Austin ◽  
Liisa A. M. Galea
Keyword(s):  
Folic Acid ◽  
Adult Female ◽  
Ventral Hippocampus ◽  
Female Rats

scholarly journals Fluoxetine Dose and Administration Method Differentially Affect Hippocampal Plasticity in Adult Female Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Jodi L. Pawluski ◽  
Eva van Donkelaar ◽  
Zipporah Abrams ◽  
Virginie Houbart ◽  
Marianne Fillet ◽  
...  
Keyword(s):  
Adult Female ◽  
Female Rats ◽  
Granule Cell Layer ◽  
Female Rat ◽  
Sprague Dawley ◽  
Osmotic Minipump ◽  
Hippocampal Plasticity ◽  
Fluoxetine Treatment ◽  
Administration Method ◽  
Administration Methods

Selective serotonin reuptake inhibitor medications are one of the most common treatments for mood disorders. In humans, these medications are taken orally, usually once per day. Unfortunately, administration of antidepressant medications in rodent models is often through injection, oral gavage, or minipump implant, all relatively stressful procedures. The aim of the present study was to investigate how administration of the commonly used SSRI, fluoxetine, via a wafer cookie, compares to fluoxetine administration using an osmotic minipump, with regards to serum drug levels and hippocampal plasticity. For this experiment, adult female Sprague-Dawley rats were divided over the two administration methods: (1) cookie and (2) osmotic minipump and three fluoxetine treatment doses: 0, 5, or 10 mg/kg/day. Results show that a fluoxetine dose of 5 mg/kg/day, but not 10 mg/kg/day, results in comparable serum levels of fluoxetine and its active metabolite norfluoxetine between the two administration methods. Furthermore, minipump administration of fluoxetine resulted in higher levels of cell proliferation in the granule cell layer (GCL) at a 5 mg dose compared to a 10 mg dose. Synaptophysin expression in the GCL, but not CA3, was significantly lower after fluoxetine treatment, regardless of administration method. These data suggest that the administration method and dose of fluoxetine can differentially affect hippocampal plasticity in the adult female rat.

scholarly journals Prenatal choline availability modulates hippocampal neurogenesis and neurogenic responses to enriching experiences in adult female rats

2007 ◽  
Vol 25 (8) ◽  
pp. 2473-2482 ◽  
Author(s):  
Melissa J. Glenn ◽  
Erin M. Gibson ◽  
Elizabeth D. Kirby ◽  
Tiffany J. Mellott ◽  
Jan K. Blusztajn ◽  
...  
Keyword(s):  
Adult Female ◽  
Hippocampal Neurogenesis ◽  
Female Rats

scholarly journals Reactive, Adult Neurogenesis From Increased Neural Progenitor Cell Proliferation Following Alcohol Dependence in Female Rats

2021 ◽  
Vol 15 ◽  
Author(s):  
Natalie N. Nawarawong ◽  
K. Ryan Thompson ◽  
Steven P. Guerin ◽  
Chinchusha Anasooya Shaji ◽  
Hui Peng ◽  
...  
Keyword(s):  
Alcohol Dependence ◽  
Dentate Gyrus ◽  
Adult Neurogenesis ◽  
Progenitor Cell ◽  
Neural Progenitor Cell ◽  
Neural Progenitor ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Female Rats ◽  
Immature Neurons

Hippocampal neurodegeneration is a consequence of excessive alcohol drinking in alcohol use disorders (AUDs), however, recent studies suggest that females may be more susceptible to alcohol-induced brain damage. Adult hippocampal neurogenesis is now well accepted to contribute to hippocampal integrity and is known to be affected by alcohol in humans as well as in animal models of AUDs. In male rats, a reactive increase in adult hippocampal neurogenesis has been observed during abstinence from alcohol dependence, a phenomenon that may underlie recovery of hippocampal structure and function. It is unknown whether reactive neurogenesis occurs in females. Therefore, adult female rats were exposed to a 4-day binge model of alcohol dependence followed by 7 or 14 days of abstinence. Immunohistochemistry (IHC) was used to assess neural progenitor cell (NPC) proliferation (BrdU and Ki67), the percentage of increased NPC activation (Sox2+/Ki67+), the number of immature neurons (NeuroD1), and ectopic dentate gyrus granule cells (Prox1). On day seven of abstinence, ethanol-treated females showed a significant increase in BrdU+ and Ki67+ cells in the subgranular zone of the dentate gyrus (SGZ), as well as greater activation of NPCs (Sox2+/Ki67+) into active cycling. At day 14 of abstinence, there was a significant increase in the number of immature neurons (NeuroD1+) though no evidence of ectopic neurogenesis according to either NeuroD1 or Prox1 immunoreactivity. Altogether, these data suggest that alcohol dependence produces similar reactive increases in NPC proliferation and adult neurogenesis. Thus, reactive, adult neurogenesis may be a means of recovery for the hippocampus after alcohol dependence in females.

scholarly journals Prenatal Inflammation Dampens Neurogenesis and Enhances Serotonin Transporter Expression in the Hippocampus of Adult Female Rats

2019 ◽  
Vol 28 (4) ◽  
pp. 352-360 ◽  
Author(s):  
Abdeslam Mouihate ◽  
Samah Kalakh ◽  
Rawan AlMutairi ◽  
Abdelrahman Alashqar
Keyword(s):  
Adult Female ◽  
Female Offspring ◽  
Hippocampal Neurogenesis ◽  
Female Rats ◽  
Pregnant Rats ◽  
Plus Maze ◽  
Age Dependent ◽  
Prenatal Inflammation ◽  
The Impact ◽  
Transporter Expression

Background/Aims: Prenatal exposure to lipopolysaccharide (LPS) dampens hippocampal neurogenesis. This effect is associated with increased anxiety-like behavior in adult offspring. Furthermore, blocking serotonin transporters (SERT) promotes adult neurogenesis. Previous studies were performed largely in males. Therefore, we explored the impact of prenatal LPS on neurogenesis, SERT expression in the hippocampus, and anxiety-like behavior in female rats during prepubertal and adulthood stages. Materials and Methods: Timed pregnant rats were injected with either saline or LPS (100 µg/kg, i.p.) on gestational days 15, 17, and 19. Newly born neurons were monitored by immunohistochemistry, and anxiety-like behavior was monitored using the elevated plus maze and open-field test. SERT expression in the hippocampus was assessed by Western blot and immunofluorescence. Results: Prenatal LPS led to reduced hippocampal neurogenesis in adult but not in prepubertal female offspring. This reduced neurogenesis was associated with enhanced hippocampal expression of SERT protein. However, there was no significant impact of prenatal LPS on anxiety-like behavior. Conclusions: Prenatal LPS-induced reduction in neurogenesis was dissociated from anxiety-like behavior in adult female rats. Furthermore, the long-lasting impact of prenatal LPS on neurogenesis in female offspring was age-dependent.

scholarly journals Sex Differences in Maturation and Attrition of Adult Neurogenesis in the Hippocampus

2019 ◽  
Author(s):  
Shunya Yagi ◽  
Jared E.J. Splinter ◽  
Daria Tai ◽  
Sarah Wong ◽  
Yanhua Wen ◽  
...  
Keyword(s):  
Sex Differences ◽  
Dentate Gyrus ◽  
Adult Neurogenesis ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Female Rats ◽  
Sprague Dawley ◽  
Male And Female Rats ◽  
Maturation Rate ◽  
Adult Born Neurons

ABSTRACTSex differences exist in the regulation of adult neurogenesis in the hippocampus in response to hormones and cognitive training. Here we investigated the trajectory and maturation rate of adult-born neurons in the dentate gyrus (DG) of male and female rats. Sprague-Dawley rats were perfused two hours, 24 hours, one, two or three weeks after BrdU injection, a DNA synthesis marker that labels dividing progenitor cells and their progeny. Adult-born neurons (BrdU/NeuN-ir) matured faster in males compared to females. Males had a greater density of neural stem cells (Sox2-ir) in the dorsal, but not in the ventral, DG and had higher levels of cell proliferation (Ki67-ir) than non-proestrous females. However, males showed a greater reduction in neurogenesis between one and two weeks after mitosis, whereas females showed similar levels of neurogenesis throughout the weeks. The faster maturation and greater attrition of new neurons in males compared to females suggests greater potential for neurogenesis to respond to external stimuli in males and emphasizes the importance of studying sex on adult hippocampal neurogenesis.Significance StatementPreviously studies examining the characteristics of adult-born neurons in the dentate gyrus have used almost exclusively male subjects. Researchers have assumed the two sexes have a similar maturation and attrition of new neurons in the dentate gyrus of adults. However, this study highlights notable sex differences in the attrition, maturation rate and potential of neurogenesis in the adult hippocampus that has significant implications for the field of neuroplasticity. These findings are important in understanding the relevance of sex differences in the regulation of neurogenesis in the hippocampus in response to stimuli or experience and may have consequences for our understanding of diseases that involve neurodegeneration of the hippocampus, particularly those that involve sex differences, such as Alzheimer’s disease and depression.

scholarly journals The effects of folic acid supplementation during pregnancy in the rat

1978 ◽  
Vol 40 (3) ◽  
pp. 529-533 ◽  
Author(s):  
B. L. G. Morgan ◽  
M. Winick
Keyword(s):  
Folic Acid ◽  
Nucleic Acid ◽  
Folic Acid Supplementation ◽  
Diet Group ◽  
Female Rats ◽  
Sprague Dawley ◽  
Products Of Conception ◽  
Group A ◽  
Nucleic Acid Biosynthesis ◽  
Rate Limiting

1. Twenty-four Sprague-Dawley female rats were randomly assigned to three groups (groups A, B, C). Group A was given a folic acid-free diet and groups B and C received 0.0018 g folic acid/kg diet. Rats in group C were also given a supplement of 1 mg folic acid/d by intraperitoneal injection.2. After 14 d of feeding the rats were mated. The diets were continued throughout gestation. On day 21, of gestation the dams were killed and their livers and products of conception assayed for RNA, DNA, protein and tetrahydrofolate dehydrogenase (5,6,7,8-tetrahydrofolate dehydrogenase; EC1.5.1.3) activity.3. The foetuses, placentas and livers from supplemented rats (group C) were significantly larger than those from groups A and B and had a higher content of RNA, DNA and protein. Those tissues from group A dams were smaller than those from the other groups and had a correspondingly reduced nucleic acid and protein content.4. The activity of tetrahydrofolate dehydrogenase, the first and rate-limiting enzyme in the metabolism of folate, was increased in the folate supplemented rats (group C) and reduced in the rats given a folic acid-free diet (group A). These changes in enzyme activity could explain the differences in nucleic acid biosynthesis and growth shown by the different groups.

Maternal Folic Acid Supplementation During Pregnancy Promotes Neurogenesis and Synaptogenesis in Neonatal Rat Offspring

2018 ◽  
Vol 29 (8) ◽  
pp. 3390-3397 ◽  
Author(s):  
Xinyan Wang ◽  
Wen Li ◽  
Zhenshu Li ◽  
Yue Ma ◽  
Jing Yan ◽  
...  
Keyword(s):  
Folic Acid ◽  
Neuronal Differentiation ◽  
Folic Acid Supplementation ◽  
Normal Diet ◽  
Hippocampal Neurogenesis ◽  
Neonatal Rat ◽  
Female Rats ◽  
Deficient Diet ◽  
Acid Supplementation ◽  
Periconceptional Period

Abstract Maternal folic acid supplementation during pregnancy is associated with improved cognitive performances in offspring. However, the effect of supplementation on offspring’s neurogenesis and synaptogenesis is unknown, and whether supplementation should be continued throughout pregnancy is controversial. In present study, 3 groups of female rats were fed a folate-normal diet, folate-deficient diet, or folate-supplemented diet from 1 week before mating until the end of pregnancy. A fourth group fed folate-normal diet from 1 week before mating until mating, then fed folate-supplemented diet for 10 consecutive days, then fed folate-normal diet until the end of pregnancy. Offspring were sacrificed on postnatal day 0 for measurement of neurogenesis and synaptogenesis by immunofluorescence and western blot. Additionally neural stem cells (NSCs) were cultured from offspring’s hippocampus for immunocytochemical measurement of their rates of proliferation and neuronal differentiation. The results demonstrated that maternal folic acid supplementation stimulated hippocampal neurogenesis by increasing proliferation and neuronal differentiation of NSCs, and also enhanced synaptogenesis in cerebral cortex of neonatal offspring. Hippocampal neurogenesis was stimulated more when supplementation was continued throughout pregnancy instead of being limited to the periconceptional period. In conclusion, maternal folic acid supplementation, especially if continued throughout pregnancy, improves neurogenesis and synaptogenesis in neonatal offspring.

Sign in / Sign up

Export Citation Format

Share Document