Unknown,Transcriptomics,Genomics,Proteomics

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Estradiol facilitates functional integration of induced pluripotent stem cell-derived dopaminergic neurons into striatal neuronal circuits via activation of integrin Î±5Î²1

ABSTRACT: To realize cell transplantation therapy for Parkinson's disease (PD), the grafted neurons should be integrated into the host neuronal circuit in order to restore the lost neuronal function. Here, using wheat germ agglutinin-based trans-synaptic tracing, we show that integrin Î±5 is selectively expressed in striatal neurons that are innervated by midbrain dopaminergic (DA) neurons from the mouse experiments. Additionally, we found that integrin Î±5Î²1 was activated by the administration of estradiol-2-benzoate (E2B) in striatal neurons of adult female rats. Importantly, we observed that the systemic administration of E2B into hemi-parkinsonian rat models facilitates the functional integration of grafted DA neurons derived from human induced pluripotent stem cells into the host striatal neuronal circuit via the activation of integrin Î±5Î²1. Finally, methamphetamine-induced abnormal rotation was recovered earlier in E2B-administrated rats than in rats that received other regimens. Our results suggest that the simultaneous administration of E2B with stem cell-derived DA progenitors can enhance the efficacy of cell transplantation therapy for PD. 0.5 ÂµL of 1% WGA Alexa Fluor 488 solution was stereotactically injected into the bilateral SNpc (from the bregma: A -3.0, L Â±1.2, V -4.2 and TB 0) of mouse. Two days after injection, a striatum sample was dissected from the mouse brain and dissociated into a single cell population by Accumax (Innovated Cell Technologies, Inc., CA, USA). To separate a two-cell population, Alexa Fluor 488+ cells and Alexa Fluor 488- cells were sorted using a FACSAria III cell sorter. Dead cells were identified and eliminated by 7-amino-actinomycin D (7-AAD) staining.

ORGANISM(S): Mus musculus

SUBMITTER: Kaneyasu Nishimura

PROVIDER: E-GEOD-77274 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Vagal afferent neurons are thought to convey primarily physiological information, whereas spinal afferents transmit noxious signals from the viscera to the central nervous system. In order to elucidate molecular identities for these different properties, we compared gene expression profiles of neurons located in nodose ganglia (NG) and dorsal root ganglia (DRG) in mice. Intraperitoneal administration of Alexa Fluor-488 conjugated Cholera toxin B allowed identification of neurons projecting to the viscera. Fluorescent neurons in DRG (from T10 to T13) and NG were isolated using laser capture microdissection. Gene expression profiles of visceral afferent neurons, obtained by microarray hybridization, were analysed using multivariate spectral map analysis, SAM algorithm (Significance Analysis of Microarray data) and fold-difference filtering. A total of 1996 genes were found to be differentially expressed in DRG versus NG, including 41 G-protein coupled receptors and 60 ion channels. Expression profiles obtained on laser-captured neurons were contrasted to those obtained on whole ganglia demonstrating striking differences and the need for microdissection when studying visceral sensory neurons because of dilution of the signal by somatic sensory neurons. Furthermore, a detailed catalogue of all adrenergic and cholinergic, GABA, glutamate, serotonin and dopamine receptors, voltage-gated potassium, sodium and calcium channels and transient receptor potential cation channels present in visceral afferents is provided. Our genome-wide expression profiling data provide novel insight into molecular signatures that underlie both functional differences and similarities between NG and DRG visceral sensory neurons. Moreover, these findings will offer novel insight into mode of action of pharmacologic agents modulating visceral sensation. Experiment Overall Design: Three separate experiments were performed. First, 5 whole dorsal root ganglia were compared to 7 whole nodose ganglia. Second, Laser captured visceral neurons derived from 5 dorsal root ganglia and 5 nodose ganglia were compared on MG-U74Av2. Third, Laser captured visceral neurons derived from 9 dorsal root ganglia and 11 nodose ganglia were compared on Mouse430_2.

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Estradiol facilitates functional integration of induced pluripotent stem cell-derived dopaminergic neurons into striatal neuronal circuits via activation of integrin Î±5Î²1

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