Dataset Information

Disruption of Selenium Handling During Puberty Causes Sex-Specific Neurological Impairments in Mice.

ABSTRACT: Selenium is an essential trace element linked to normal development and antioxidant defense mechanisms through its incorporation into selenoproteins via the amino acid, selenocysteine (Sec). Male mice lacking both the Se transporter, selenoprotein P (SELENOP), and selenocysteine lyase (Scly), which plays a role in intracellular Se utilization, require Se supplementation for viability and exhibit neuromotor deficits. Previously, we demonstrated that male SELENOP/Scly double knockout (DKO) mice suffer from loss of motor function and audiogenic seizures due to neurodegeneration, both of which are alleviated by prepubescent castration. The current study examined the neuromotor function of female DKO mice using the rotarod and open field test, as well as the effects of dietary Se restriction. Female DKO mice exhibited a milder form of neurological impairment than their male counterparts. This impairment is exacerbated by removal of Se supplementation during puberty. These results indicate there is a critical time frame in which Se supplementation is essential for neurodevelopment. These sex-specific differences may unveil new insights into dietary requirements for this essential nutrient in humans.

SUBMITTER: Kremer PM

PROVIDER: S-EPMC6523490 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Disruption of Selenium Handling During Puberty Causes Sex-Specific Neurological Impairments in Mice.

Kremer Penny M PM Torres Daniel J DJ Hashimoto Ann C AC Berry Marla J MJ

Antioxidants (Basel, Switzerland) 20190424 4

Selenium is an essential trace element linked to normal development and antioxidant defense mechanisms through its incorporation into selenoproteins via the amino acid, selenocysteine (Sec). Male mice lacking both the Se transporter, selenoprotein P (SELENOP), and selenocysteine lyase (Scly), which plays a role in intracellular Se utilization, require Se supplementation for viability and exhibit neuromotor deficits. Previously, we demonstrated that male SELENOP/Scly double knockout (DKO) mice su ...[more]

PMID: 31022880

Similar Datasets

Project description:Meiosis expressed gene 1 (Meig1) was originally identified in a search for mammalian genes potentially involved in meiosis. Seven mouse Meig1 transcripts with the same coding region, but different 5'-UTRs, have been identified. These transcripts have different tissue distributions, two are only present in the testis. In the testis, Meig1 is present in germ cells and Sertoli cells. A Meig1 conditional knockout model has been generated. When Meig1 was inactivated globally by crossing with Cmv-Cre transgenic mice, the Meig1-deficient males were sterile due to severe spermiogenic defects, and had no obvious defects in meiosis. To further study its role in individual cell types in the testis, the Meig1(flox) mice were crossed with Hsp2a-Cre, Prm-Cre, and Amh-Cre mice, in which the Cre recombinase is driven by the heat shock protein 2 (Hsp2a) gene promoter (expressed in spermatocytes), the protamine 1 gene promoter (expressed in post-meiotic spermatids) and the anti-Mullerian hormone (Amh) gene promoter (expressed in Sertoli cells) respectively. Both Meig1 mRNA and protein were undetectable in testis of the Hsp2a-Cre; Meig1(flox/flox) mice and all the mutant adult males tested were sterile. This phenotype mirrors that of the Cmv-Cre; Meig1(flox/flox) mice. Even though the total testicular Meig1 mRNA and protein expression levels were dramatically reduced in testis of the Prm-Cre; Meig1(flox/flox) males, all the mice tested were fertile, and there was no significant difference in sperm count and sperm motility compared with age-matched Meig1(flox/flox) male mice. Disruption of Meig1 in the Sertoli cells did not affect the MEIG1 protein expression. Amh-Cre; Meig1(flox/flox) males were fertile, and produced the same amount of spermatozoa as age-matched Meig1(flox/flox) mice. The testicular histology was also normal. Our results indicate that MEIG1 regulates spermiogenesis through effects in germ cells alone, and that the Meig1 gene must be active during a discrete period in spermatogenesis after which it is dispensable.

Project description:Background: Neurological impairment (NI) and disability are associated with reduced life expectancy, but the risk and magnitude of premature mortality in children vary considerably across study settings. We conducted a systematic review to estimate the magnitude of premature mortality following childhood-onset NI worldwide and to summarize known risk factors and causes of death. Methods: We searched various databases for published studies from their inception up to 31st October 2020. We included all cohort studies that assessed the overall risk of mortality in individuals with childhood-onset epilepsy, intellectual disability (ID), and deficits in hearing, vision and motor functions. Comparative measures of mortality such as the standardized mortality ratio (SMR), risk factors and causes were synthesized quantitatively under each domain of impairment. This review is registered on the PROSPERO database (registration number CRD42019119239). Results: The search identified 2,159 studies, of which 24 studies were included in the final synthesis. Twenty-two (91.7%) studies originated from high-income countries (HICs). The median SMR was higher for epilepsy compared with ID (7.1 [range 3.1-22.4] vs. 2.9 [range 2.0-11.6]). In epilepsy, mortality was highest among younger age groups, comorbid neurological disorders, generalized seizures (at univariable levels), untreatable epilepsy, soon after diagnosis and among cases with structural/metabolic types, but there were no differences by sex. Most deaths (87.5%) were caused by non-epilepsy-related causes. For ID, mortality was highest in younger age groups and girls had a higher risk compared to the general population. Important risk factors for premature mortality were severe-to-profound severity, congenital disorders e.g., Down Syndrome, comorbid neurological disorders and adverse pregnancy and perinatal events. Respiratory infections and comorbid neurological disorders were the leading causes of death in ID. Mortality is infrequently examined in impairments of vision, hearing and motor functions. Summary: The risk of premature mortality is elevated in individuals with childhood-onset NI, particularly in epilepsy and lower in ID, with a need for more studies for vision, hearing, and motor impairments. Survival in NI could be improved through interventions targeting modifiable risk factors and underlying causes.

Dataset Information

Disruption of Selenium Handling During Puberty Causes Sex-Specific Neurological Impairments in Mice.

Publications

Disruption of Selenium Handling During Puberty Causes Sex-Specific Neurological Impairments in Mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets