Search Results (2)

The Ataxin-2-like (ATXN2L) protein is required to survive embryonic development, as documented in mice with the constitutive absence of the ATXN2L Lsm, LsmAD, and PAM2 domains due to knock-out (KO) of exons 5–8 with a frameshift. Its less abundant paralog, Ataxin-2 (ATXN2), has an extended N-terminus, where a polyglutamine domain is prone to expansions, mediating vulnerability to the polygenic adult motor neuron disease ALS (Amyotrophic Lateral Sclerosis) or causing the monogenic neurodegenerative processes of Spinocerebellar Ataxia Type 2 (SCA2), depending on larger mutation sizes. Here, we elucidated the physiological function of ATXN2L by deleting the LsmAD and PAM2 motifs via loxP-mediated KO of exons 10–17 with a frameshift. Crossing heterozygous floxed mice with constitutive Cre-deleter animals confirmed embryonic lethality among offspring. Crossing with CamK2a-CreERT2 mice and injecting tamoxifen for conditional deletion achieved chimeric ATXN2L absence in CamK2a-positive frontal cortex neurons and reduced spontaneous horizontal movement. Global proteome profiling of frontal cortex homogenate showed ATXN2L levels decreased to 75% and dysregulations enriched in the alternative splicing pathway. Nuclear proteins with Sm domains are critical to performing splicing; therefore, our data suggest that the Like-Sm (Lsm, LsmAD) domains in ATXN2L serve a role in splice regulation, despite their perinuclear location. Full article

Extremely low frequency electromagnetic field (ELF-EMF) exists widely in public and occupational environments. However, its potential adverse effects and the underlying mechanism on nervous system, especially behavior are still poorly understood. In this study, zebrafish embryos (including a transfected synapsin IIa (syn2a) overexpression plasmid) at 3 h post-fertilization (hpf) were exposed to a 50-Hz magnetic field (MF) with a series of intensities (100, 200, 400 and 800 μT, respectively) for 1 h or 24 h every day for 5 days. Results showed that, although MF exposure did not affect the basic development parameters including hatching rate, mortality and malformation rate, yet MF at 200 μT could significantly induce spontaneous movement (SM) hypoactivity in zebrafish larvae. Histological examination presented morphological abnormalities of the brain such as condensed cell nucleus and cytoplasm, increased intercellular space. Moreover, exposure to MF at 200 μT inhibited syn2a transcription and expression, and increased reactive oxygen species (ROS) level as well. Overexpression of syn2a could effectively rescue MF-induced SM hypoactivity in zebrafish. Pretreatment with N-acetyl-L-cysteine (NAC) could not only recover syn2a protein expression which was weakened by MF exposure, but also abolish MF-induced SM hypoactivity. However, syn2a overexpression did not affect MF-increased ROS. Taken together, the findings suggested that exposure to a 50-Hz MF inhibited spontaneous movement of zebrafish larvae via ROS-mediated syn2a expression in a nonlinear manner. Full article