Dataset Information

Gene expression profiling of rat postnatal 4 cortex following gestational exposure to 4-Methylimidazole (4-MeI) and maternal seizures.

ABSTRACT: Compromised maternal health and specifically, the occurrence of maternal seizures can have adverse effects on the healthy development of offspring possibly via hypoxia-ischemia, disrupted programmed cell death, or GABA signaling. The current study examined cortical tissue from F2b postnatal day 4 offspring of female Harlan SD rats following a two-generation reproductive and continuous breeding (RACB) study design with daily oral exposure to the seizure genic compound 4-Methylimidazole (0, 750, or 2500 ppm 4-MeI). mRNA levels were determined by qRT-PCR for GABA related genes and by whole genome microarray for differential gene expression (DGE) profiles. While maternal seizures occurred at 2500 ppm, there was no indication of disrupted GABA or glutamatergic signaling. At 750 ppm, DGE suggested adaptation or developmental delay. At 2500 ppm, DGE suggested an impact on critically timed structural events such as synaptogenesis and membrane stability/signaling. Pathways related to growth process and cell signaling showed a negative activation supporting an interpretation of disruption or delay in developmental processes. Further examination across multiple post-partum and preweaning ages for an evaluation of the temporal sequence of development will provide better foundation for biological interpretation.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE231378 | GEO | 2023/11/22

REPOSITORIES: GEO

ACCESS DATA

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

Project description:Succinate semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessive disorder effecting approximately 350 people around the world. Patients suffering from SSADH deficiency experience language acquisition failure, memory deficiencies, autism, increased aggressive behaviors, and seizures. There is a chemical buildup of both gamma-aminobutyric acid (GABA) and gamma-hydroxybutyric acid (GHB) in the neurological system of these patients. The Aldh5a1-/- knock out mouse model of SSADH deficiency shows the same chemical imbalances as the human disease, with additional fatal tonic-clonic seizures at three weeks of age. The elucidation of seizure causing pathways will facilitate treatment of seizure phenotypes in diseases with related epilepsy. Gene expression patterns within the hippocampus, cerebellum, and cortex of SSADH deficient mice (Aldh5a1-/- mice) will be compared to wild type mice at a time point immediately prior to fatal seizures. We hypothesis that the SSADH deficient mice experience a dysfunction of glutamate/GABA/ glutamine neurotransmitter cycle linked to astroglial metabolism and/or uptake of neuronally-released glutamate. The increased levels of GHB and GABA lead to down regulation of GABA-B-Receptor leading to seizures. The SSADH deficient phenotype may also be caused by ongoing oxidative damage and the pathological role of succinic semialdehyde. SSADH deficient mice (Aldh5a1-/- knock out) exhibit fatal seizures around three weeks of age. Mutant and wild type mice will be sacrificed between 17 and 19 days of life, and brain sections will be extracted and frozen (using a standard protocol). Hippocampus, cerebellum, and cortex from three mutant mice and three wild type mice will individually be expression profiled on the Affymetrix platform, giving a total of eighteen arrays. Comparative analysis will then be carried out, evaluating the transcript differences between mutant and wild type mice in each brain region. Keywords: other