Background and purpose: Parkinson's disease is a common degenerative disease of the central nervous system with complex pathogenesis. More and more studies have found that inflammatory response promotes the occurrence and development of the disease, in which the activation of microglia plays an important role. PGC-1α (peroxisome proliferator activated receptor-γ coactivator-1α) is the main factor in mitochondrial biogenetic, and is closely related to the inflammatory response. Our immunofluorescence test results showed that PGC-1α and microglia (Iba1) have double-labeled phenomenon. The expression of microglia in the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) group increased, and PGC-1α/Iba1 double label increased. To test whether lowering the expression of PGC-1α can reduce the activation of microglia and protect the substantia nigra dopaminergic neurons, we constructed PGC-1α interference lentivirus.Methods: Immunofluorescence, western blot, and ELISA were used to detect microglial phenotype.Results: The results showed that PGC-1α interfering with lentivirus can transfect microglial cells in substantia nigra, and the PGC-1α protein level decreased in substantia nigra accordingly; TH protein expression had no statistical difference compared with MPTP group; PGC-1α interfering lentivirus reduced microglia number and activation, and at the same time the expression of iNOS and Arg1 significantly reduced compared with MPTP group. The IL-6 expression in blood detected using ELISA was significantly reduced compared with MPTP group.Conclusion: PGC-1α downregulation inhibited microglia activity, and both M1 and M2 microglial activities are reduced.
Objective: To explore the signal pathways of acupoint stimulation and reveal the underlying mechanisms in the treatment of tinnitus.Methods: Thirty-two SD adult rats were randomly divided into four groups: control group(n=8),non-point group(n=8),Yifeng(TE17) point group(n=8),and Fengchi(GB20) point group(n=8).Non-point group rats,Fengchi(GB20) and Yifeng(TE17) experimental groups were stimulated with acupuncture needle for 20 minutes under anesthesia,while the control group was not given any simulation.Two hours later,all rats were perfused,and the brains were removed and immersed in sucroser.Then the brains were sectioned serially with freezing microtome.Immunohistochemistry technique was used to show the Fos-LI neurons.The distribution and amount of Fos-LI neurons were observed under the microscope.Results: In the Fengchi(GB20) point group,Fos-LI neurons were distributed in the left and right lateral segment of Sp5C specifically;in the Yifeng(TE17) point group,Fos-LI neurons were distributed in the left lateral and ventral segment of Sp5I specifically.There were a large number of Fos-LI neurons in brainstem auditory nuclei,specifically in DCN and VCN.Fos-LI neurons were also specifically distributed in the nuclei of median raphe,such as Rob,RMg and DR.Conclusion: Signals of needling Fengchi(GB20) and Yifeng(TE17) have the specific pathway to the spinal trigeminal nucleus and can activate the neurons in auditory center and raphe nuclei.It is indicated that the afferent signal of point stimulation of Yifeng(TE17) and Fengchi(GB20) can affect the activity of central auditory system and the raphe system neurons.
Although many pathogenic copy number variations (CNVs) are associated with neuropsychiatric diseases, few of them have been functionally characterised. Here we report multiple schizophrenia cases with CNV abnormalities specific to unc-51-like kinase 4 (ULK4), a novel serine/threonine kinase gene. Deletions spanning exons 21–34 of ULK4 were present in 4 out of 3,391 schizophrenia patients from the International Schizophrenia Consortium, but absent in 3,181 controls. Deletions removing exons 33 and 34 of the large splice variant of ULK4 also were enriched in Icelandic schizophrenia and bipolar patients compared to 98,022 controls (P=0.0007 for schizophrenia plus bipolar disorder). Combining the two cohorts gives a p value less than 0.0001 for schizophrenia, or for schizophrenia plus bipolar disorder. The expression of ULK4 is neuron-specific and developmentally regulated. ULK4 modulates multiple signalling pathways including ERK, p38, PKC, and JNK, which are involved in stress responses and implicated in schizophrenia. Knockdown of ULK4 disrupts the composition of microtubules and compromises neuritogenesis and cell motility. Targeted Ulk4 deletion causes corpus callosum agenesis in mice. Our findings indicate that ULK4 is a rare susceptibility gene for schizophrenia.
Tinnitus is the conscious experience of sound without an external acoustic source. Many years of research effort have contributed to a better understanding of the mechanisms underlying tinnitus, including the neural correlates of tinnitus. Our laboratory has been investigating the modulatory effects of somatosensory and cortical electrical stimulation on the neural correlates of tinnitus in auditory and nonauditory structures. These aspects of tinnitus suppression research are explored in an effort to stimulate further studies and to promote the development of effective strategies in the management of tinnitus through electrical stimulation.
There were extensive efferent and afferent projections in the ventrolateral medulla.The ventrolateral medulla play a key role in the modulation of blood pressure,respiration,pain and so on.The study summarized the results got in the research of the functions and neural pathway of the ventrolateral medulla in last years.
The aim of the present study was to gain insight into the neuroprotection effects and mechanism of thiazolidinedione pioglitazone in both in vitro and in vivo MPP+/MPTP induced PD models. In vivo experimental results showed that oral treatment of pioglitazone resulted in significant improvements in behavior symptoms damaged by MPTP and increase in the survival of TH positive neurons in the pioglitazone intervention groups. In addition, oral treatment of pioglitazone increased the expression of peroxisome proliferator-activated receptor-γ coactivator of 1α (PGC-1α) and increased the number of mitochondria, along with an observed improvement in mitochondrial ultrastructure. From in vitro studies, 2,4-thiazolidinedione resulted in increased levels of molecules regulated function of mitochondria, including PGC-1α, nuclear respiratory factor 1 (NRF1), NRF2, and mitochondria fusion 2 (Mfn2), and inhibited mitochondria fission 1 (Fis1). We show that protein levels of Bcl-2 and ERK were reduced in the MPP+-treated group compared with the control group. This effect was observed to be reversed upon treatment with 2,4-thiazolidinedione, as Bcl-2 and ERK expression levels were increased. We also observed that levels of the apoptotic protein Bax showed opposite changes compared to Bcl-2 and ERK levels. The results from this study confirm that pioglitazone/2,4-thiazolidinedione is able to activate PGC-1α and prevent damage of dopaminergic neurons and restore mitochondria ultrastructure through the regulation of mitochondria function.
Motion sickness (MS) is a disorder of the autonomic nervous system caused by abnormal exercise with symptoms such as nausea, vomiting and drowsiness. More than 90% of the human population has experienced different degrees of MS. At present, anticholinergics, antihistamines, and sympathomimetic drugs are used for treating MS, but these drugs generally have some adverse reactions and are not suitable for all people. Therefore, it is necessary to develop anti-MS drugs that have high efficiency and no adverse effects. Previous studies have found that Chroogomphus rutilus polysaccharide (CRP) is effective at preventing and treating MS in rats and mice. However, its mechanism of action is not clear. To clarify whether the CRP has anti-MS effects in mice, and to clarify its mechanism, we performed behavioral, biochemical, and morphological tests in a Kunming mouse model. Our results indicate that CRPs can significantly relieve the symptoms of MS, and their effect is equivalent to that of scopolamine, a commonly used anti-MS medicine. Our results indicate that CRPs may directly act on the gastrointestinal chromaffin cells to inhibit the synthesis and release of serotonin (5-hydroxytryptamine, or 5-HT) and thus reduce the signal from the gastrointestinal tract.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)
'%3e%3ccircle r='20' fill='%23008'/%3e%3ccircle r='17.5' fill='%23fff'/%3e%3ccircle r='3.5' fill='%23008'/%3e%3cg id='d'%3e%3cg id='c'%3e%3cg id='b'%3e%3cg id='a' fill='%23008'%3e%3ccircle r='.875' transform='rotate(7.5 -8.75 133.5)'/%3e%3cpath d='M0 17.5.6 7 0 2l-.6 5L0 17.5z'/%3e%3c/g%3e%3cuse xlink:href='%23a' transform='rotate(15)'/%3e%3c/g%3e%3cuse xlink:href='%23b' transform='rotate(30)'/%3e%3c/g%3e%3cuse xlink:href='%23c' transform='rotate(60)'/%3e%3c/g%3e%3cuse xlink:href='%23d' transform='rotate(120)'/%3e%3cuse xlink:href='%23d' transform='rotate(-120)'/%3e%3c/g%3e%3c/svg%3e)
'/%3e%3cpath d='M200 752.362h200v300H200z' style='fill:%23fff;fill-opacity:1;stroke:none' transform='translate(0 -752.362)'/%3e%3cpath d='M400 752.362h200v300H400z' style='fill:%23ff883e;fill-opacity:1;stroke:none' transform='translate(0 -752.362)'/%3e%3c/svg%3e)