ABSTRACT
The visual system plays an important role in our daily life. In this study, we found that loss of dendritic cell factor 1 (DCF1) in the primary visual cortex (V1) caused a sight deficit in mice and induced an abnormal increase in glutamic acid decarboxylase 67, an enzyme that catalyzes the decarboxylation of glutamate to gamma aminobutyric acid and CO, particularly in layer 5. In vivo electrophysiological recordings confirmed a decrease in delta, theta, and beta oscillation power in DCF1-knockout mice. This study presents a previously unknown function of DCF1 in V1, suggests an unknown contact between DCF1 and GABA systems, and provides insight into the mechanism and treatment of visual deficits.
Subject(s)
Animals , Mice , Brain Waves , Genetics , Disease Models, Animal , Electroencephalography , Gene Expression Regulation , Genetics , Geniculate Bodies , Metabolism , Ginkgolides , Therapeutic Uses , Glutamate Decarboxylase , Metabolism , Lactones , Therapeutic Uses , Membrane Proteins , Genetics , Mice, Inbred C57BL , Mice, Knockout , Nerve Tissue Proteins , Genetics , Photic Stimulation , Proto-Oncogene Proteins c-fos , Metabolism , Vision Disorders , Drug Therapy , Genetics , Pathology , Visual Cortex , Metabolism , Pathology , gamma-Aminobutyric Acid , MetabolismABSTRACT
Objective To observe the effects of long term injection sodium salicylate on the auditory brain-stem response(ABR)and expression of glutamic acid decarboxylase -67(GAD67) in rat inferior colliculus .Methods Eighteen healthy Wistar rats were randomly divided into three groups :the sodium salicylate group (intramuscular injection of 10% sodium salicylate ,175 mg/kg ,twice daliy for 28 days) ,the saline group (intramuscular injection with saline on same does at the same time) ,the control group (without any treatment) .The rats received ABR after modeling ,then were decapitated and inferior colliculus tissues were stripped .Western blot was used to study the dif-ferent expression of GAD67 protein levels in the three groups .Results Compared with the saline group and control group ,ABR thresholds of the sodium salicylate group were significantly elevated and latency of wave Ⅲ was aslo sig-nificantly prolonged(P0 .05) .The inferior colliculus GAD67 protein expression level of sodium salicylate group was significantly higher than the saline group and control group(P0 .05) .Conclusion Long term injection of sodium salicylate can cause a change in the inferior colliculus of GAD67 protein expression and the up regulation of GAD67 expression may occur as a com-pensatory response to increase inhibiting effect .The change of GAD67 protein expression is likely as a compensatory and regulatory mechanisms for sodium salicylate ototoxicity .
ABSTRACT
Impairment in spinal inhibition caused by quantitative alteration of GABAergic elements following peripheral nerve injury has been postulated to mediate neuropathic pain. In the present study, we tested whether neuropathic pain could be induced or reversed by pharmacologically modulating spinal GABAergic activity, and whether quantitative alteration of spinal GABAergic elements after peripheral nerve injury was related to the impairment of GABAergic inhibition or neuropathic pain. To these aims, we first analyzed the pain behaviors following the spinal administration of GABA antagonists (1 microgram bicuculline/rat and 5 microgram phaclofen/rat), agonists (1 microgram muscimol/rat and 0.5 microgram baclofen/rat) or GABA transporter (GAT) inhibitors (20 microgram NNC-711/rat and 1 microgram SNAP-5114/rat) into naive or neuropathic animals. Then, using Western blotting, PCR or immunohistochemistry, we compared the quantities of spinal GABA, its synthesizing enzymes (GAD65, 67) and its receptors (GABAA and GABAB) and transporters (GAT-1, and -3) between two groups of rats with different severity of neuropathic pain following partial injury of tail-innervating nerves; the allodynic and non-allodynic groups. Intrathecal administration of GABA antagonists markedly lowered tail-withdrawal threshold in naive animals, and GABA agonists or GAT inhibitors significantly attenuated neuropathic pain in nerve-injured animals. However, any quantitative changes in spinal GABAergic elements were not observed in both the allodynic and non-allodynic groups. These results suggest that although the impairment in spinal GABAergic inhibition may play a role in mediation of neuropathic pain, it is not accomplished by the quantitative change in spinal elements for GABAergic inhibition and therefore these elements are not related to the generation of neuropathic pain following peripheral nerve injury.
Subject(s)
Animals , Rats , Blotting, Western , GABA Agonists , GABA Antagonists , gamma-Aminobutyric Acid , Immunohistochemistry , Negotiating , Neuralgia , Peptides , Peripheral Nerve Injuries , Polymerase Chain ReactionABSTRACT
Objective To observe the distribution of GABA-containing neurons revealed by GFP expression and the colocalization of the GFP with parvalbumin(PV) in the caudal spinal trigeminal nucleus(Vc),the glutamate decarboxylase 67-green fluorescence protein(GAD67-GFP) knock-in mice were used in the present study. Methods Double-labeled techniques were used by in situ hybridization combined with immunohistochemistry for GFP and double immunofluorescence histochemistry for GFP and NeuN(neuronal nuclei protein,a neuronal marker) or PV.The stained sections were observed under light microscope and a confocal laser-scanning microscope. Results 1.Over 90% of GFP-positive neuronal cell bodies in the laminae Ⅰ and Ⅱ of the Vc showed hybridization signals for GAD67 mRNA,and that almost all neuronal cell bodies with GAD67 mRNA signals were GFP-positive;2.GFP-positive neurons were mainly distributed in the laminae Ⅰ and Ⅱ of the Vc and the vast majority of them were small neurons.The considerable number of GFP-positive processes and somata were most densely observed in the lamina Ⅱ of the Vc.The proportion of GFP-positive neurons in the NeuN-labeled neurons of the Vc was about 19.4% and 24.3% in laminae Ⅰ and Ⅱ,respectively;3.Double-labeled neurons for GFP/PV are mainly found in laminae Ⅰ and Ⅱ of the Vc.The proportion of GFP/PV double-labeled neurons was about 62.4% and 12.8% of total population of PV-and GFP-positive neurons in laminae Ⅰ-Ⅱ of the Vc,respectively.Conclusion GABAergic neurons are mainly distributed in the laminae Ⅰ and Ⅱ of the Vc which related closely to transmission of the nociceptive primary afferent information,and the majority of PV-positive neurons are GABAergic neurons.