Homeostatic Regulation of Seizure Susceptibility and Cognitive Function by ER Quality Controller Derlin-1 through Maintenance of Adult Neurogenesis
Murao, N.; Matsuda, T.; Kadowaki, H.; Matsushita, Y.; Tanimoto, K.; Katagiri, T.; Nakashima, K.; Nishitoh, H.
Show abstract
Dysfunction of organelle is closely associated with neurological diseases involving disruption of adult neurogenesis. However, the role of the endoplasmic reticulum (ER)-related molecules in this process remains largely unexplored. Here we show that Derlin-1, an ER quality controller, maintains adult neurogenesis in a spatiotemporal manner. Deletion of Derlin-1 in the mouse central nervous system induces ectopic localization of newborn neurons and impairs neural stem cells (NSCs) transition from active to quiescent states, resulting in early depletion of hippocampal NSCs. As a result, Derlin-1- deficient mice exhibit phenotypes of increased seizure susceptibility and impaired cognitive function. Reduced expression of signal transducer and activator of transcription 5b (Stat5b) was found to be responsible for the impairment of adult neurogenesis in Derlin-1-deficient NSCs. Remarkably, the inhibition of histone deacetylase activity ameliorated seizure susceptibility and cognitive dysfunction in Derlin-1-deficient mice by increasing Stat5b expression and restoring abnormal neurogenesis. Overall, our findings demonstrate that Derlin-1, as its characteristic function, plays an essential role in the homeostasis of adult neurogenesis via Stat5b expression, thus regulating seizure susceptibility and cognitive function.
Matching journals
The top 9 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Shh from mossy cells contributes to preventing NSC pool depletion after seizure-induced neurogenesis and in aging 97%
- 7-Dehydrocholesterol-derived oxysterols cause neurogenic defects in Smith-Lemli-Opitz syndrome 95%
- Constitutively active STING causes neuroinflammation and degeneration of dopaminergic neurons in mice 94%
Similar papers in this journal
- Fluctuation of lysosomal protein degradation in neural stem cells of postnatal mouse brain 96%
- Wnt/beta-catenin signalling is dispensable for adult neural stem cell homeostasis and activation. 96%
- Sox9 and Nfi transcription factors regulate the timing of neurogenesis and ependymal maturation in dopamine progenitors 95%
Similar papers in this journal
- The transcription factor ZEB1 regulates stem cell self-renewal and astroglial fate in the adult hippocampus 96%
- Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum 94%
- Role of PARP1 in oligodendrocyte differentiation during developmental myelination and remyelination after myelin damage 94%
Similar papers in this journal
- Dispensable regulation of brain development and myelination by the immune-related protein Serpina3n 95%
- Specific detection and deletion of the Sigma-1 receptor in neurons and glial cells for functional characterization in vivo 95%
- Troriluzole Rescues Glutamatergic Deficits, Amyloid and Tau Pathology, and Synaptic and Memory Impairments in 3xTg-AD Mice 94%
Similar papers in this journal
- Neuronal kinase SGK1.1 protects against brain damage after status epilepticus 94%
- Arfgef1 haploinsufficiency in mice alters neuronal endosome composition and decreases membrane surface postsynaptic GABAA receptors 94%
- Long-term hippocampal low-frequency stimulation alleviates focal seizures, memory deficits and synaptic pathology in epileptic mice 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.