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Circadian regulation of Limulus visual functions:A role for octopamine and cAMP

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Current Zoology 2010年第5期56卷 518-536页

作者： Jasbir S.DALAL Barbara-Anne BATTELLE Whitney Laboratory for Marine Bioscience and the Departments of Neuroscience and Biology University of Florida Department of Internal Medicine and Division of Human Nutrition and Metabolic Diseases University of Texas Southwestern Medical Center

The purpose of this contribution is to review our current understanding of the source and biochemistry of the circadian efferent input to the eyes of the American horseshoe crab Limuluspolyphemus and the impact of this input on the structure, physiology and biochemistry of Limulus eyes. Special emphasis is given to the role of the biogenic amine octopamine and bio- chemical cascades it activates in the eyes. In addition to reviewing published data, we present new data showing that octopamine elevates cAMP levels in Limulus lateral eyes, and we partially characterize the pharmacology of the receptors involved in this response. We also present new data showing that octopamine regulates gene expression in Limulus lateral eyes by activating a cAMP cascade

关键词： Horseshoe crab Circadian rhythms Oetopamine Photoreceptors Substance P Arrestin

Wnt/β-catenin signaling in midbrain dopaminergic neuron specification and neurogenesis

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Journal of Molecular Cell Biology 2014年第1期8卷 27-33页

作者： Milan Joksimovic Rajeshwar Awatramani Department of Cell Biology Neurobiology and Anatomy Medical College of Wisconsin 8701_ Watertown Plank Road Milwaukee Wl 53226-0509 USA Department of Neurology and Center for Genetic Medicine Northwestern University 303 E Superior Street Chicago IL 6061.1 USA

Loss of midbrain dopaminergic （mDA） neurons underlies the motor symptoms of Parkinson＇s disease. Towards cell replacement, studies have focused on mechanisms underlying embryonic mDA production, as a rational basis for deriving mDA neurons from stem cells. We will review studies of [3-catenin, an obligate component of the Wnt cascade that is critical to mDA specification and neuro- genesis, mDA neurons have a unique origin--the midbrain fLoor plate （FP）. Unlike the hindbrain and spinal cord FP, the midbrain FP is highly neurogenic and Wnt/β-catenin signaling is critical to this difference in neurogenic potential. In β-catenin loss-of-function experiments, the midbrain FP resembles the hindbrain FP, and key mDA progenitor genes such as Otx2, Lmxlo, MsxJ, and Ngn2 are downregulated whereas Shh is maintained. Accordingly, the neurogenic capacity of the midbrain FP is diminished, resulting in fewer mDA neurons. Conversely, in β-catenin *** experiments, the hindbrain FP expresses key mDA progenitor genes, and is highly neurogenic. Interestingly, when excessive β-catenin is supplied to the midbrain FP, less mDA neurons are produced sug- gesting that the dosage ofWntJ β-catenin signaling is critical. These studies of β-catenin have facilitated new protocols to derive mDA neurons from stem cells.

关键词： wnt β-catenin dopamine specification neurogenesis

Transcriptional regulators that differentially control dendrite and axon development

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Frontiers in Biology 2012年第4期7卷 292-296页

作者： Xin WANG Bing YE Life Sciences Institute University of Michigan Ann Arbor MI 48109 USA Department of Cell and Developmental Biology University of Michigan Ann Arbor MI 48109 USA Department of Molecular Cellular and Developmental Biology University of Michigan Ann Arbor MI 48109 USA

Neurons are the basic units of connectivity in the nervous system. As a signature feature, neurons form polarized structures： dendrites and axons, which integrate either sensory stimuli or inputs from upstream neurons and send outputs to target cells, respectively. The separation of dendritic and axonal compartments is achieved in two steps during development： 1） dendrite and axon specification： how neurites are initially specified as dendrites and axons; and 2） dendrite and axon commitment： how dendrites and axons are committed to distinct compartmental fates and architectures. To understand neural circuit assembly and to correct erroneous dendrite or axon growth in a compartment-specific manner, it is essential to understand the regulatory mechanisms underlying dendrite and axon commitment. Compared to extensive studies on dendrite and axon specification, little is known about the molecular mechanisms exclusively dedicated to dendrite or axon commitment. Recent studies have uncovered the requirement of transcriptional regulation in this process. Here, we review the studies on transcriptional regulators： Darl, p300-SnoN, NeuroD, which have been shown to separate dendrite- and axon-specific growth of the same neuron type after compartmental fates are specified.

关键词： dendrite and axon commitment Darl p300-SnoN NeuroD

Activity-dependent signaling mechanisms regulating adult hippocampal neural stem cells and their progeny

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Neuroscience Bulletin 2014年第4期30卷 542-556页

作者： Andrew J.Crowther Juan Song Graduate Program of Neurobiology Curriculum University of North CarolinaChapel HillNC 27599USA Department of Pharmacology University of North CarolinaChapel HillNC 27599USA Neuroscience Center/Neurobiology Curriculum University of North CarolinaChapel HillNC 27599USA School of Medicine University of North CarolinaChapel HillNC 27599USA

Adult neural stem cells （NSCs） reside in a restricted microenvironment, where their development is controlled by subtle and presently underexplored cues. This raises a significant question： what instructions must be provided by this supporting niche to regulate NSC development and functions？ Signaling from the niche is proposed to control many aspects of NSC behavior, including balancing the quiescence and proliferation of NSCs, determining the cell division mode （symmetric versus asymmetric）, and preventing premature depletion of stem cells to maintain neurogenesis throughout life. Interactions between neurogenic niches and NSCs also govern the homeostatic regulation of adult neurogenesis under diverse physiological, environmental, and pathological conditions. An important implication from revisiting many previously-identified regulatory factors is that most of them （e.g., the antidepressant fluoxetine and exercise） affect gross neurogenesis by acting downstream of NSCs at the level of intermediate progenitors and neuroblasts, while leaving the NSC pool unaffected. Therefore, it is critically important to address how various niche components, signaling pathways, and environmental stimuli differentially regulate distinct stages of adult neurogenesis.

关键词： neural stem cell neuronal development neuronal plasticity

Diazepam reduces synaptic GABA type areceptor availability via multiple trafficking mechanisms

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中国药理学与毒理学杂志 2017年第10期31卷 952-952页

作者： Joshua M LORENZ-GUERTIN Sabyasachi DAS Tija C JACOB Department of Pharmacology & Chemical Biology University of Pittsburgh

OBJECTIVE Investigate the effects of diazepam(DZP) on γ2 subunit containing GABA type A receptor(GABA A R) *** Immunofluorescence microscopy measured surface GABA A Rs and gephyrin in rat cortical neurons after 24 h exposure of 1.0 μmol·L^(-1) *** studies of mice injected with 10 mg·kg^(-1) DZP vs vehicle were assessed for γ2 subunit and total gephyrin cortical levels 12 h *** of the γ2 subunit was studied by immunoprecipitation after 12 h of 1.0 μmol·L^(-1) DZP exposure.A γ2 subunit encoding an N terminal fluorogen-activating peptide and pH-sensitive green fluorescent protein(γ2 pH FAP) measured lysosomal targeting of γ2 containing GABA A ***-gephyrin and γ2 pH FAP synaptic diffusion rates were examined using fluorescence recovery after photobleaching(FRAP).RESULTS Extrasynaptic levels of γ2 GABA A Rs decreased by 12.2%,while synaptic gephyrin S270 phosphorylation increased by 18.3% in DZP-treated neurons after 24 h compared to control(P<0.05).Dendritic levels of gephyrin were also reduced to 74.1% of control,while S270 phosphorylation was elevated by 25.2%(P<0.05;P<0.01).Mice 12 h post-DZP injection demonstrated a 12.7% and 26.1% decrease in total γ2 and gephyrin levels,respectively(P<0.05;P<0.01).12 h DZP treatment enhanced γ2 subunit ubiquitination 1.13-fold relative to control(P<0.05).Internalized γ2 pH FAP GABA A Rs associated with lysosomes was 8.0% higher in neurons treated with 12-16 h DZP compared to *** FRAP experiments suggest gephyrin and γ2 have increased mobility and turnover at synapses following *** DZP treatment decreases γ2 GABA A R levels and gephyrin scaffolding function after one day of exposure,which may contribute to the formation of DZP tolerance.

关键词： GABA type A receptor gephyrin trafficking diazepam