Androgens and the developing hippocampus

Kight, Katherine E.; McCarthy, Margaret M.

doi:10.1186/s13293-020-00307-6

Cited by 37 publications

(22 citation statements)

References 165 publications

(192 reference statements)

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“…The hippocampus is a critical brain region for regulating both the physiological response to stress, by mediating negative feedback control on glucocorticoid release, and to the process of forming and storing memories, particularly those that include a spatial component. These divergent and complex functions also differ in males and females in a variety of ways that depend on life stage, context and past experience [ 24 ]. Sex differences in neurophysiological parameters in the adult hippocampus abound [ 25 , 26 ], including aspects of adult neurogenesis [ 26 ], but there has been relatively little attention paid to the potential for sex differences in the hippocampus as it develops.…”

Section: Discussionmentioning

confidence: 99%

Neurogenesis in the neonatal rat hippocampus is regulated by sexually dimorphic epigenetic modifiers

et al. 2022

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Background Neurogenesis in the hippocampus endures across the lifespan but is particularly prolific during the first postnatal week in the developing rodent brain. The majority of new born neurons are in the dentate gyrus (DG). The number of new neurons born during the first postnatal week in the DG of male rat pups is about double the number in females. In other systems, the rate of cell proliferation is controlled by epigenetic modifications in stem cells. We, therefore, explored the potential impact of DNA methylation and histone acetylation on cell genesis in the developing DG of male and female rats. Methods Cell genesis was assessed by quantification of BrdU + cells in the DG of neonatal rats following injections on multiple days. Methylation and acetylation were manipulated pharmacologically by injection of well vetted drugs. DNA methylation, histone acetylation and associated enzyme activity were measured using commercially available colorimetric assays. mRNA was quantified by PCR. Multiple group comparisons were made by one- or two-way ANOVA followed by post-hoc tests controlling for multiple comparisons. Two groups were compared by t test. Results We found higher levels of DNA methylation in male DG and treatment with the DNA methylating enzyme inhibitor zebularine reduced the methylation and correspondingly reduced cell genesis. The same treatment had no impact on either measure in females. By contrast, treatment with a histone deacetylase inhibitor, trichostatin-A, increased histone acetylation in the DG of both sexes but increased cell genesis only in females. Females had higher baseline histone deacetylase activity and greater inhibition in response to trichostatin-A treatment. The mRNA levels of the proproliferative gene brain-derived neurotrophic factor were greater in males and reduced by inhibiting both DNA methylation and histone deacetylation only in males. Conclusions These data reveal a sexually dimorphic epigenetically based regulation of neurogenesis in the DG but the mechanisms establishing the distinct regulation involving DNA methylation in males and histone acetylation in females is unknown.

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Section: Discussionmentioning

confidence: 99%

Neurogenesis in the neonatal rat hippocampus is regulated by sexually dimorphic epigenetic modifiers

et al. 2022

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“…Steroid hormones, including testosterone and aromatization of testosterone to estrogen, is essential in regulating many key neural functions. [105][106][107][108] Reductions in these steroid hormones, especially estrogen, is linked to later neurobehavioral disorders, such as Alzheimer's Disease. 105,106 Biosynthesis of unsaturated fatty acids is another pathway likely reduced in response to increases in Prevotella spp.…”

Section: Discussionmentioning

confidence: 99%

Developmental Exposure to Silver Nanoparticles Leads to Long Term Gut Dysbiosis and Neurobehavioral Alterations

Lyu

Ghoshdastidar

Rekha

et al. 2020

Preprint

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Due to their antimicrobial properties, silver nanoparticles (NPs) are used in a wide range of consumer products that includes topical wound dressings, coatings for biomedical devices, and food-packaging to extend the shelf-life. Despite their beneficial antimicrobial effects, developmental exposure to such NPs may lead to gut dysbiosis and long-term health consequences in exposed offspring. Silver NPs can cross the placenta and blood-brain-barrier to translocate in the brain of offspring. The underlying hypothesis tested in the current study was that developmental exposure of male and female mice to silver NPs disrupts the microbiome-gut-brain axis. To examine for such effects, C57BL6 female mice were exposed orally to silver NPs at a dose of 3 mg/kg BW or vehicle control two weeks prior to breeding and throughout gestation. Male and female offspring were tested in various mazes that measure different behavioral domains, and the gut microbial profiles were surveyed from 30 through 120 days of age. Our study results suggest that developmental exposure results in increased likelihood of engaging in repetitive behaviors and reductions in resident microglial cells. Echo-MRI results indicate increased body fat in offspring exposed to NP exhibit. Coprobacillus spp., Mucispirillum spp., and Bifidobacterium spp. were reduced, while Prevotella spp., Bacillus spp., Planococcaceae, Staphylococcus spp., Enterococcus spp., and Ruminococcus spp. were increased in those developmentally exposed to NPs. These bacterial changes were linked to behavioral and metabolic alterations. In conclusion, developmental exposure of silver NPs results in long term gut dysbiosis, body fat increase and neurobehavioral alterations in offspring.

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“…Androgens such as testosterone and dihydrotestosterone enhance the survival of immature hippocampal neurons in adult male rodents ( Duarte-Guterman, 2019 , Hamson et al, 2013 , Spritzer and Galea, 2007 ), and estrogens have similar effects in adult female rodents ( Barha et al, 2009 , Mazzucco et al, 2006 ). Estrogens and androgens also promote morphological maturation of adult-born granule cell neurons, evidenced by increased dendritic complexity and spine density ( Hatanaka et al, 2015 , Kight and McCarthy, 2020 , Sheppard et al, 2019 ). In the rodent medial amygdala, androgens increase the number of excitatory synapses during puberty ( Cooke and Woolley, 2009 , Cooke, 2011 ).…”

Section: Developmental Processes In the Plmentioning

confidence: 99%