Front Cell Neurosci
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Front Cell Neurosci · Jan 2015
Age- and sex-dependent susceptibility to phenobarbital-resistant neonatal seizures: role of chloride co-transporters.
Ischemia in the immature brain is an important cause of neonatal seizures. Temporal evolution of acquired neonatal seizures and their response to anticonvulsants are of great interest, given the unreliability of the clinical correlates and poor efficacy of first-line anti-seizure drugs. The expression and function of the electroneutral chloride co-transporters KCC2 and NKCC1 influence the anti-seizure efficacy of GABAA-agonists. ⋯ This study established a novel neonatal mouse model of PB-resistant seizures that demonstrates age/sex-dependent susceptibility. The age-dependent profile of KCC2 expression and its post-insult downregulation may underlie the PB-resistance reported in this model. Blocking NKCC1 with low-dose BTN following PB treatment failed to improve PB-efficacy.
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Front Cell Neurosci · Jan 2015
Neto2-null mice have impaired GABAergic inhibition and are susceptible to seizures.
Neto2 is a transmembrane protein that interacts with the neuron-specific K(+)-Cl(-) cotransporter (KCC2) in the central nervous system (CNS). Efficient KCC2 transport is essential for setting the neuronal Cl(-) gradient, which is required for fast GABAergic inhibition. Neto2 is required to maintain the normal abundance of KCC2 in neurons, and increases KCC2 function by binding to the active oligomeric form of this cotransporter. ⋯ To examine GABAergic inhibition we recorded spontaneous inhibitory postsynaptic currents (sIPSCs) and found that Neto2(-/-) neurons had significant reductions in both their amplitude and frequency. Based on the critical role of Neto2 in regulating GABAergic inhibition we rationalized that Neto2-null mice would be prone to seizure activity. We found that Neto2-null mice demonstrated a decrease in the latency to pentylenetetrazole (PTZ)-induced seizures and an increase in seizure severity.
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Front Cell Neurosci · Jan 2015
A novel rat model of blast-induced traumatic brain injury simulating different damage degree: implications for morphological, neurological, and biomarker changes.
In current military conflicts and civilian terrorism, blast-induced traumatic brain injury (bTBI) is the primary cause of neurotrauma. However, the effects and mechanisms of bTBI are poorly understood. Although previous researchers have made significant contributions to establishing animal models for the simulation of bTBI, the precision and controllability of blast-induced injury in animal models must be improved. ⋯ Compared with the moderate injury group, there were significantly more neurological dysfunctions, cortical contusions, intraparenchymal hemorrhages, cortical expression of S-100β, myelin basic protein, neuron-specific enolase, IL-8, IL-10, inducible nitric oxide synthase, and HIF-1α in the severe injury group. These results demonstrate that we have created a reliable and reproducible bTBI model in rats. This model will be helpful for studying the mechanisms of bTBI and developing strategies for clinical bTBI treatment.
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Front Cell Neurosci · Jan 2015
ReviewAdapting for endocytosis: roles for endocytic sorting adaptors in directing neural development.
Proper cortical development depends on the orchestrated actions of a multitude of guidance receptors and adhesion molecules and their downstream signaling. The levels of these receptors on the surface and their precise locations can greatly affect guidance outcomes. ⋯ We will discuss the cell biology of regulated endocytosis and the impact on neural development. We focus our discussion on endocytic accessory proteins (EAPs) (such as numb and disabled) and how they regulate endocytosis and subsequent post-endocytic trafficking of their cognate receptors (such as Notch, TrkB, β-APP, VLDLR, and ApoER2).
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Front Cell Neurosci · Jan 2015
ReviewCellular and Deafness Mechanisms Underlying Connexin Mutation-Induced Hearing Loss - A Common Hereditary Deafness.
Hearing loss due to mutations in the connexin gene family, which encodes gap junctional proteins, is a common form of hereditary deafness. In particular, connexin 26 (Cx26, GJB2) mutations are responsible for ~50% of non-syndromic hearing loss, which is the highest incidence of genetic disease. In the clinic, Cx26 mutations cause various auditory phenotypes ranging from profound congenital deafness at birth to mild, progressive hearing loss in late childhood. ⋯ However, the detailed cellular mechanisms underlying these pathological changes remain unclear. Also, little is known about specific mutation-induced pathological changes in vivo and little information is available for humans. Such further studies are urgently required.