RESUMO
There is intensive gap-junctional coupling between glial processes, but their significance in sensory functions remains unknown. Connexin-43 (Cx43), a major component of astrocytic gap-junction channels, is abundantly expressed in astrocytes. To investigate the role of Cx43-mediated gap junctions between astrocytes in sensory functions, we generated Cx43 knockout (KO) mice with a mouse line carrying loxP sites flanking exon 2 of the Cx43 gene and the transgenic line expressing Cre recombinase under control of the glial fibrillary acidic protein promoter, which exhibited a significant loss of Cx43 in astrocytes in the barrel cortex. Although Cx43 expression between the astrocytes measured by immunohistochemistry was virtually abolished in Cx43 KO mice, they had normal architecture in the barrel cortex but the intensity of cytochrome oxide histochemistry decreased significantly. In vivo electrophysiological analysis revealed that the long-term potentiation of the vibrissal evoked responses in the barrel cortex evoked by high-frequency rhythmic vibrissal stimuli (100 Hz, 1 s) was abolished in Cx43 KO mice. Current source density analysis also revealed that astrocytic Cx43 was important to the flow of excitation within the laminar connections in barrel cortex. Behavioral tests showed that the ability of Cx43 KO mice to sense the environment with their whiskers decreased. Even so, the jump-stand experiment showed that they could still discriminate rough from smooth surfaces. Our findings suggest that Cx43-mediated gap-junctional coupling between astrocytes is important in the neuron-glia interactions required for whisker-related sensory functions and plasticity.
Assuntos
Astrócitos/fisiologia , Conexina 43/metabolismo , Potenciais Somatossensoriais Evocados , Deleção de Genes , Potenciação de Longa Duração , Córtex Somatossensorial/fisiologia , Animais , Astrócitos/metabolismo , Conexina 43/genética , Junções Comunicantes/metabolismo , Camundongos , Neurônios/fisiologia , Córtex Somatossensorial/citologia , Córtex Somatossensorial/metabolismo , Vibrissas/inervação , Vibrissas/fisiologiaRESUMO
Interactions between neurons and glial cells in the brain have important roles in brain functions such as development and plasticity of neural circuits or functions. Glial cells are much more actively involved in brain functions than previously thought. Here, we used vibrissal stimuli to induce sensoryevoked responses and multiunit spikes in the contralateral barrel cortex in a rat model. Local application of the gliotoxin DL-alpha-aminoadipate (AA) revealed that glial cells were involved in the sensoryevoked responses. The increases in the amplitude of somatosensory-evoked potential (SEP) and multiunit sensory-evoked spike rates in barrel cortex after AA injection were dramatic. Immunohistochemical staining of brain lipid binding protein (BLBP) and NeuN showed AA decreased cell number of astrocytes but not neurons in the barrel cortex. In conclusion, our results suggested an important role for astrocyte metabolism in normal synaptic activities.
Assuntos
Neuroglia/fisiologia , Vibrissas/fisiologia , Ácido 2-Aminoadípico/farmacologia , Trifosfato de Adenosina/metabolismo , Animais , Astrócitos/fisiologia , Potenciais Somatossensoriais Evocados , Feminino , Masculino , Ratos , Ratos Sprague-Dawley , Córtex Somatossensorial/fisiologiaRESUMO
Gap junction is the aggregate of some intercellular channels, which allows ions and small molecules to transport or transfer between cells. There are about 20 proposed members of the connexin family found in mammalian tissues now, and more than 10 reported are expressed in the nervous system. The astrocytes and oligodendrocytes express some specific connexins. In the present article, we review the recent literatures to illustrate the importance of gap junction for the intercellular communication between glial cells, astrocytes and neurons, and neuronal cells, which is crucial for brain functions.
Assuntos
Encéfalo/fisiologia , Junções Comunicantes/metabolismo , Encéfalo/metabolismo , Conexinas/metabolismo , Junções Comunicantes/fisiologia , Humanos , Neuroglia/metabolismo , Neuroglia/fisiologia , Neurônios/metabolismo , Neurônios/fisiologiaRESUMO
Pyrophosphate synthetase-1(PRS-1) is a crucial enzyme that catalyzes the synthesis of phosphoribosylpyrophosphate (PRPP) with substrate: adenosine triphosphate (ATP) and ribose-5-phophate(R5P) in the de novo pathways of purine and pyrimidine nucleotide synthesis. Mutation in PRPS1 can result in a series of diseases of purine metabolism, which includes PRS-1 superactivity. The common clinical phenotypes are hyperuricemia and hyperuricosuria. We identified a novel missense mutation in X-chromosomal gene PRPS1 in a young Chinese woman while her mother has heterogeneous genotype and phenotype. A 24-year-old Chinese female patient suffered hyperuricemia, gout, and recurrent hyperpyrexia for more than 6 years, and then was diagnosed with hyperandrogenism, insulin resistance (IR), and polycystic ovary syndrome (PCOS). A novel missense mutation, c.521(exon)G>T, p.(Gly174Val) was detected by next-generation sequencing (NGS) and confirmed by Sanger sequencing in the patient and her parents. Interestingly, her mother has the same heterozygous missense mutation but without uric acid overproduction which can be explained by the phenomenon of the skewed X-chromosome inactivation. The substituted amino acid Val for Gly174 is positioned in the pyrophosphate (PPi) binding loop, and this mutation impacts the binding rate of Mg2+-ATP complex to PRS-1, thus the assembling of homodimer is affected by changed Val174 leading to the instability of the allosteric site. Our report highlights the X-linked inheritance of gout in females caused by mutation in PRPS1 accompanied with severe metabolic disorders and recurrent hyperpyrexia.