Mice Exposed to Combined Chronic Low-Dose Irradiation and Modeled Microgravity Develop Long-Term Neurological Sequelae.
Eliah G OverbeyAmber M PaulWillian A da SilveiraCandice G T TahimicSigrid S ReinschNathaniel J SzewczykSeta StanboulyCharles WangJonathan M GalazkaXiao Wen MaoPublished in: International journal of molecular sciences (2019)
Spaceflight poses many challenges for humans. Ground-based analogs typically focus on single parameters of spaceflight and their associated acute effects. This study assesses the long-term transcriptional effects following single and combination spaceflight analog conditions using the mouse model: simulated microgravity via hindlimb unloading (HLU) and/or low-dose γ-ray irradiation (LDR) for 21 days, followed by 4 months of readaptation. Changes in gene expression and epigenetic modifications in brain samples during readaptation were analyzed by whole transcriptome shotgun sequencing (RNA-seq) and reduced representation bisulfite sequencing (RRBS). The results showed minimal gene expression and cytosine methylation alterations at 4 months readaptation within single treatment conditions of HLU or LDR. In contrast, following combined HLU+LDR, gene expression and promoter methylation analyses showed multiple altered pathways involved in neurogenesis and neuroplasticity, the regulation of neuropeptides, and cellular signaling. In brief, neurological readaptation following combined chronic LDR and HLU is a dynamic process that involves pathways that regulate neuronal function and structure and may lead to late onset neurological sequelae.
Keyphrases
- gene expression
- dna methylation
- rna seq
- single cell
- low dose
- late onset
- cerebral ischemia
- genome wide
- mouse model
- early onset
- blood brain barrier
- magnetic resonance
- magnetic resonance imaging
- radiation therapy
- transcription factor
- computed tomography
- brain injury
- skeletal muscle
- metabolic syndrome
- oxidative stress
- smoking cessation
- multiple sclerosis
- molecular docking
- intensive care unit
- neural stem cells
- molecular dynamics simulations
- type diabetes
- aortic dissection
- high fat diet induced
- heat shock protein