Effect of stromal cell-derived factor-1/CXCR4 axis in neural stem cell transplantation for Parkinson’s disease

Previous studies have shown that neural stem cell transplantation has the potential to treat Parkinson’s disease,but its specific mechanism of action is still unclear.Stromal cell-derived factor-1 and its receptor,chemokine receptor 4(CXCR4),are important regulators of cell migration.We speculated that the CXCR4/stromal cell-derived factor 1 axis may be involved in the therapeutic effect of neural stem cell transplantation in the treatment of Parkinson’s disease.A Parkinson’s disease rat model was injected with 6-hydroxydopamine via the right ascending nigrostriatal dopaminergic pathway,and then treated with 5μL of neural stem cell suspension(1.5×104/L)in the right substantia nigra.Rats were intraperitoneally injected once daily for 3 days with 1.25 mL/kg of the CXCR4 antagonist AMD3100 to observe changes after neural stem cell transplantation.Parkinson-like behavior in rats was detected using apomorphine-induced rotation.Immunofluorescence staining was used to determine the immunoreactivity of tyrosine hydroxylase,CXCR4,and stromal cell-derived factor-1 in the brain.Using quantitative real-time polymerase chain reaction,the mRNA expression of stromal cell-derived factor-1 and CXCR4 in the right substantia nigra were measured.In addition,western blot assays were performed to analyze the protein expression of stromal cell-derived factor-1 and CXCR4.Our results demonstrated that neural stem cell transplantation noticeably reduced apomorphine-induced rotation,increased the mRNA and protein expression of stromal cell-derived factor-1 and CXCR4 in the right substantia nigra,and enhanced the immunoreactivity of tyrosine hydroxylase,CXCR4,and stromal cell-derived factor-1 in the brain.Injection of AMD3100 inhibited the aforementioned effects.These findings suggest that the stromal cell-derived factor-1/CXCR4 axis may play a significant role in the therapeutic effect of neural stem cell transplantation in a rat model of Parkinson’s disease.This study was approved by the Animal Care and Use Committee of Kunming Medical University,China(approval No.SYXKK2015-0002)on April 1,2014.     

Organization of ventral tegmental area cells projecting to the occipital cortex and forebrain in the rat

Our horseradish peroxidase retrograde tracing study revealed a specific subpopulation of ventral tegmental area (VTA) neurons that send axons to the occipital cortex in the rat. A fluorescent retrograde tracing study demonstrated that neuronal populations in the VTA projecting to the occipital cortex are distributed in a manner separate from those projecting to forebrain structures such as the frontal/anterior cingulate cortices and nucleus accumbens. The scarcity of collateral projections from the VTA contrasts with the extensive collateralization of projection neurons in the substantia nigra pars compacta. Projections to the occipital cortex may define the distribution of cells comprising the VTA and thus the clear hodological separation of the A9 and A10 dopamine cell groups.     

Monoaminergic synapses,including dendro-dendritic synapses in the rat substantia nigra

Summary Intraventricular administration of 1 or 2 mg of the osmiophilic false transmitter 5-hydroxydopamine (5-OHDA) was used to label monoamine storage and release sites in the rat substantia nigra. Vesicles containing unusually dense cores indicative of the presence of the marker were seen forming from the Golgi apparatus in the cell bodies of medium-sized neurons of the substantia nigra, pars compacta, and from smooth endoplasmic reticulum in the dendrites of those neurons and in small unmyelinated axons of unknown origin. In serial sections, both axons and dendrites containing synaptic vesicles marked with 5-OHDA were seen to form synapses en passage in pars compacta, and some presynaptic dendrites containing vesicles filled by the marker were also observed to form contacts with dendrites in pars reticulata. The only identified postsynaptic elements engaging in monoaminergic synapses in the substantia nigra were dendrites of medium-sized pars compacta neurons.     

Topography of the auditory evoked potential in humans reflects differences between vowels embedded in pseudo-words

To study the processing of vowels embedded in more complex linguistic structures, we compared cortical responses for pseudo-words. Auditory evoked potentials were recorded in 11 right-handed females using a passive oddball paradigm, with /pemu/ and /pomu/ as standard stimuli, differing only with respect to the first syllable. Topographic differences in the N100 were observed between the standards: /pemu/ had larger amplitudes than /pomu/ at more posterior electrode sites whereas a reverse pattern was found at more anterior positions along the midline. This topographic difference can be explained by different generators for the two stimuli. Different vowels and/or the initial formant transition possibly activate different neural populations in the auditory cortex, also when the vowels are embedded in pseudo-words.     

Isoprenylated phenolic compounds with tyrosinase inhibition from Morus nigra

A new isoprenylated sanggenon-type flavanone, nigrasin K (1), together with three known analogs (2–4) and five known Diels–Alder adducts (5–9), were isolated from the twigs of Morus nigra. Their structures were elucidated by spectroscopic methods. Sanggenon M (2), chalcomoracin (5), sorocein H (6), kuwanon J (7), sanggenon C (8), and sanggenon O (9) showed significant inhibitory effects on mushroom tyrosinase.     

Differentiation of the midbrain dopaminergic pathways during mouse development

Dopaminergic (DA) neurons in the substantia nigra (SN) and ventral tegmental area (VTA) of the midbrain project to the dorsolateral caudate/putamen and to the ventromedially located nucleus accumbens, respectively, establishing the mesostriatal and the mesolimbic pathways. Disruptions in this system have been implicated in Parkinson's disease, drug addiction, schizophrenia, and attention deficit hyperactivity disorder. However, progress in our understanding has been hindered by a lack of knowledge of how these pathways develop. In this study, different retrograde tracers, placed into the dorsolateral caudate/putamen and the nucleus accumbens, were used to analyze the development of the dopaminergic pathways. In embryonic day 15 mouse embryos, both SN and VTA neurons, as well as their fibers, were doubly labeled by striatal injections into the dorsolateral and ventromedial striatum. However, by birth, the SN DA neurons were labeled exclusively by DiA placed in the dorsolateral striatum, and the VTA DA neurons were labeled only by DiI injected into the ventromedial striatum. These data suggest that initial projections from midbrain DA neurons target nonspecifically to both the dorsolateral striatum and the nucleus accumbens. Later during development, the separate mesostriatal and mesolimbic pathways differentiate through the selective elimination of mistargeted collaterals.     

Loss of insulin receptor immunoreactivity from the substantia nigra pars compacta neurons in Parkinson's disease

Immunohistochemistry using both a newly developed polyclonal, and a commercially available monoclonal, anti-insulin receptor antibody was done on the midbrain from cases of idiopathic Parkinson's disease (PD), Alzheimer's disease, amyotrophic lateral sclerosis, vascular parkinsonism and non-neurological controls. Both antibodies gave indentical patterns of neuronal staining. The neurons of the oculomotor nucleus were immunopositive in all the brains. However, the neurons in the pars compacta of the substantia nigra, paranigral nucleus, parabrachial pigmental nucleus, tegmental pedunculopontine nucleus, supratrocheal nucleus, cuneiform nucleus, subcuneiform nucleus and lemniscus medialis, which were positive in other diseases and in non-neurological controls, were not stained by these antibodies in PD brains. These results suggest that, in PD, a dysfunction of the insulin/insulin receptor system may precede death of the dopaminergic neurons.The work in the Kinsmen Laboratory was supported by the MRC of Canada and the Parkinson Society of Canada     

The effects of

The effects of unilateral application of GABA (10(-5) M) into thalamic motor nuclei (ventralis medialis-ventralis lateralis, VM-VL) on 5-HT transmission in basal ganglia were investigated in halothane-anaesthetized cats implanted with several push-pull cannulae. The release of [3H]5-HT continuously synthesized from [3H]tryptophan was estimated in both caudate nuclei (CN), both substantia nigrae (SN) and in the dorsal raphe nucleus (DRN). [3H]5-HT release was decreased in the two CN and in the two SN but was enhanced in the DRN when GABA was applied into the VM-VL. These results indicate that thalamic motor nuclei are involved in a bilateral regulation of serotoninergic transmission in the basal ganglia.     

Role of thalamic motor nuclei in bilateral regulation of serotoninergic transmission in cat basal ganglia

The effects of unilateral application of GABA (10(-5) M) into thalamic motor nuclei (ventralis medialis-ventralis lateralis, VM-VL) on 5-HT transmission in basal ganglia were investigated in halothane-anaesthetized cats implanted with several push-pull cannulae. The release of [3H]5-HT continuously synthesized from [3H]tryptophan was estimated in both caudate nuclei (CN), both substantia nigrae (SN) and in the dorsal raphe nucleus (DRN). [3H]5-HT release was decreased in the two CN and in the two SN but was enhanced in the DRN when GABA was applied into the VM-VL. These results indicate that thalamic motor nuclei are involved in a bilateral regulation of serotoninergic transmission in the basal ganglia.     

Neuronal uptake of [3H]GABA and [3H]glycine in laminae I-III (substantia gelatinosa Rolandi) of the rat spinal cord. An autoradiographic study

[3H]GABA or [3H]glycine were injected into the subarachnoidal space of adult rats at C4-C5 level. After 10-60 min, the animals were perfused with 4% paraformaldehyde-0.5% glutaraldehyde and thick sections of the cervical spinal cord were postosmicated and Epon embedded. Light microscope autoradiographs of transverse cord sections showed numerous silver grains over the dorsal column and laminae I-III, higher grain densities occurring over lamina I for GABA and lamina III for glycine. In [3H]GABA-injected animals nerve cell bodies in lamina I or at the transition to lamina II appeared strongly labeled in light and electron microscope autoradiographs. These cells were smaller and less rich in RER than marginal cells and poor in axosomatic synaptic contacts. High grain densities appeared over axon terminals synapsing with dendrites in laminae I-II and over the light peripheral axon endings of synaptic glomeruli of laminae II-III. After [3H]glycine treatment, a number of nerve cell bodies were labeled in lamina III. It is suggested that two types of inhibitory interneurons occur in the rat gelatinosa, one GABAergic with cell body in lamina I, and another glycinergic in lamina III.