Front Cell Neurosci
-
Front Cell Neurosci · Jan 2017
Primary Spinal OPC Culture System from Adult Zebrafish to Study Oligodendrocyte Differentiation In Vitro.
Endogenous oligodendrocyte progenitor cells (OPCs) are a promising target to improve functional recovery after spinal cord injury (SCI) by remyelinating denuded, and therefore vulnerable, axons. Demyelination is the result of a primary insult and secondary injury, leading to conduction blocks and long-term degeneration of the axons, which subsequently can lead to the loss of their neurons. In response to SCI, dormant OPCs can be activated and subsequently start to proliferate and differentiate into mature myelinating oligodendrocytes (OLs). ⋯ In this methodology paper, we show efficient isolation of OPCs from adult zebrafish spinal cord and describe culture conditions that enable analysis up to 10 days in vitro. Finally, we demonstrate that zebrafish OPCs differentiate into Myelin Basic Protein (MBP)-expressing OLs when co-cultured with human motor neurons differentiated from induced pluripotent stem cells (iPSCs). This shows that the basic mechanisms of oligodendrocyte differentiation are conserved across species and that understanding the regulation of zebrafish OPCs can contribute to the development of new treatments to human diseases.
-
Front Cell Neurosci · Jan 2017
ReviewRegulatory Roles of Long Non-Coding RNAs in the Central Nervous System and Associated Neurodegenerative Diseases.
Accumulating studies have revealed that the human genome encodes tens of thousands of long non-coding RNAs (lncRNAs), which participate in multiple biological networks modulating gene expression via transcriptional, post-transcriptional and epigenetic regulation. Strikingly, a large fraction of tissue-specific lncRNAs are expressed in the Central Nervous System (CNS) with precisely regulated temporal and spatial expression patterns. ⋯ However, how lncRNAs contribute to these disorders remains to be further explored and studied. In this review article, we systematically and comprehensively summarize the current studies of lncRNAs, demonstrate the specificity of lncRNAs expressed in the brain, their functions during neural development and expression profiles in major cell types of the CNS, highlight the regulatory mechanisms of several studied lncRNAs that may play essential roles in the pathophysiology of neurodegenerative diseases, and discuss the current challenges and future perspectives of lncRNA studies involved in neurodegenerative and other diseases.
-
Front Cell Neurosci · Jan 2017
Mild Traumatic Brain Injury Evokes Pyramidal Neuron Axon Initial Segment Plasticity and Diffuse Presynaptic Inhibitory Terminal Loss.
The axon initial segment (AIS) is the site of action potential (AP) initiation, thus a crucial regulator of neuronal activity. In excitatory pyramidal neurons, the high density of voltage-gated sodium channels (NaV1.6) at the distal AIS regulates AP initiation. A surrogate AIS marker, ankyrin-G (ankG) is a structural protein regulating neuronal functional via clustering voltage-gated ion channels. ⋯ Also within this non-DAI population, patch-clamp recordings of intact YFP+ pyramidal neurons showed AP acceleration decreased 2 days post-mTBI, consistent with AIS functional plasticity. Simulations of realistic pyramidal neuron computational models using experimentally determined AIS lengths showed a subtle decrease is NaV1.6 density is sufficient to attenuate AP acceleration. Collectively, these findings highlight the complexity of mTBI-induced neocortical circuit disruption, involving changes in extrinsic/presynaptic inhibitory perisomatic input interfaced with intrinsic/postsynaptic intact excitatory neuron AIS output.
-
Front Cell Neurosci · Jan 2016
Rapid Eye Movement Sleep Deprivation Produces Long-Term Detrimental Effects in Spatial Memory and Modifies the Cellular Composition of the Subgranular Zone.
Sleep deprivation (SD) affects spatial memory and proliferation in the dentate gyrus. It is unknown whether these deleterious effects persist in the long run. The aim of this study was to evaluate the proliferation, differentiation and maturation of neural progenitors as well as spatial memory 21 days after suffering SD. ⋯ To date it is unknown whether these deleterious effects are persistent over a long period of time. We analyzed the effects of sleep deprivation in the hippocampus after 21 days of recovery sleep. Our findings indicate that after sleep recovery, the detrimental effects of SD can be observed for at least 2 weeks, as shown by a reduction in memory performance, changes in the hippocampal cellular composition and higher apoptotic rate over a long period of time.