Morphological Plasticity of Emerging Purkinje Cells in Response to Exogenous VEGF

Herrfurth, Leonard; Theis, Verena; Matschke, Veronika; May, Caroline; Marcus, Katrin; Theiß, Carsten

doi:10.3389/fnmol.2017.00002

Cited by 14 publications

(29 citation statements)

References 80 publications

(105 reference statements)

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“…Similarly, since cry2 and brp are connected (i.e. brp is degraded by cry2 after light stimulation 33 ), a provision of brp mRNA or translated protein at the time point of diapause termination is then necessary. We therefore anticipate that cry2 is another photoreceptor gene (besides a rhodopsin gene 25 ) that plays a significant role in the variation of timing of resting-stage induction in Daphnia .…”

Section: Discussionmentioning

confidence: 99%

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The expression of circadian clock genes in Daphnia magna diapause

Schwarzenberger

Chen

Weiss

2020

Sci Rep

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Diapause is a mechanism necessary for survival in arthropods. Often diapause induction and resurrection is light-dependent and therefore dependent on the photoperiod length and on the number of consecutive short-days. In many organisms, including the microcrustacean Daphnia magna, one functional entity with the capacity to measure seasonal changes in day-length is the circadian clock. There is a long-standing discussion that the circadian clock also controls photoperiod-induced diapause. We tested this hypothesis in D. magna, an organism which goes into a state of suspended animation with the shortening of the photoperiod. We measured gene expression of clock genes in diapause-destined embryos of D. magna in the initiation, resting and resurrection phases and checked it against gene expression levels of continuously developing embryos. We demonstrate that some genes of the clock are differentially expressed during diapause induction but not during its maintenance. Furthermore, the photoreceptor gene cry2 and the clock-associated gene brp are highly expressed during induction and early diapause, probably in order to produce excess mRNA to prepare for immediate resurrection. After resurrection, both types of embryos show a similar pattern of gene expression during development. Our study contributes significantly to the understanding of the molecular basis of diapause induction, maintenance and termination.

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Section: Discussionmentioning

confidence: 99%

“…Interestingly, brp interacts with the circadian clock although it is not part of the core circadian system 32 . Analogous to the light-dependent degradation of the circadian clock gene timeless ( tim ), it is degraded by cryptochrome 33 . Therefore, the circadian clock might play a significant role in diapause termination in Daphnia .…”

Section: Introductionmentioning

confidence: 99%

The expression of circadian clock genes in Daphnia magna diapause

Schwarzenberger

Chen

Weiss

2020

Sci Rep

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“…PC are characterized by a pronounced dendritic tree, covered with a huge number of dendritic spines, which are structurally filled out by highly dynamic actin filaments (Herrfurth et al, ). Stimulation of PC with progesterone positively affects the biosynthesis of actin within these spines (Wessel et al, ).…”

Section: Progesterone and Prsmentioning

confidence: 99%

Progesterone Effects in the Nervous System

Theis

Theiß

2019

The Anatomical Record

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The sex hormone progesterone is mainly known as a key factor in establishing and maintaining pregnancy. In addition, progesterone has been shown to induce morphological changes in the central and peripheral nervous system by increasing dendrito-, spino-, and synaptogenesis in Purkinje cells (Wessel et al.: Cell Mol Life Sci (2014a) 1723-1740 and increasing axonal outgrowth in dorsal root ganglia (Olbrich et al.: Endocrinology (2013) 3784-3795). These effects mediated mainly by the classical progesterone receptors (PRs) A and B seem to be limited to young neurons. It may be assumed that microRNAs (miRNAs), which are potent regulators of nervous system maturation and degeneration, are also involved in the regulation of progesterone-mediated neuronal plasticity by altering the expression patterns of the corresponding PR A/B receptors (Theis and Theiss: Neural Regen Res (2015) 547-549, Pieczora et al.: Cerebellum (2017) 376-387). This review critically discusses current data on the neuroprotective effect of progesterone and its corresponding receptors in the nervous system, with possible regulatory processes by miRNAs. Preclinical studies on stroke and traumatic brain injury revealed neuroprotective and neuroregenerative effects of progesterone in the treatment of severe neurological diseases in animal models, but have so far failed in humans. In this context, the identification of specific miRNAs that regulate the expression of progesterone and PR could help to exploit the neuroprotective potential of progesterone for the treatment of various neurological disorders. The human nervous system is a highly complex tissue composed of neurons and glial cells with a limited ability to regenerate after lesion or degeneration. In particular, the loss of neurons, for example, due to aging processes, stroke, or traumatic brain injury (TBI), is mostly irreversible. The function of the degenerating neurons can be partially compensated by neighboring neurons, but astroglial-fibrotic scar formation minimizes neuronal regeneration .Progesterone, a sexual hormone, is mainly known for its key role in the female reproductive circuit and the maintenance of pregnancy. In this context, the fact that progesterone is also expressed in the male organism is often neglected (Schumacher et al., 2014). Besides this, Abbreviations: BBB = blood brain barrier; CNS = central nervous system; DRG = dorsal root ganglia; GABA = Gamma-amino butyric acid; miRNA = microRNA; NMDAR = N-Methyl-D-aspartate receptor; PC = Purkinje cells; PGRMC1 = progesterone receptor membrane component 1; PNS = peripheral nervous system; PR = progesterone receptor; SCI = spinal cord injury; TBI = traumatic brain injury

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“…Through VEGFR-2, the receptor that conveys most of the VEGF-driven processes, VEGF mediates endothelial migration, and survival, vasculogenesis, and angiogenesis. VEGFR-2 is also strongly expressed in neuronal cells and plays a key role in proliferation, migration and survival as well as axonal guidance and dendritogenesis of neuronal cells [ 2 , 16 , 17 , 18 ]. Although VEGF has higher affinity to VEGFR-1 than to VEGFR-2, most of the various effects promoted by VEGFR-1, e.g., angiogenesis, haematopoiesis, neuronal survival, and inflammatory cell recruitment, are triggered by the ligand PIGF.…”

Section: Introductionmentioning

confidence: 99%

“…The impact of VEGF as a stimulator of neurogenesis during development, maturation and regeneration processes of neuronal tissue especially has been in the focus of current investigations [ 11 ]. Recent studies pointed out that VEGF is a key player for dendritogenesis, e.g., of Purkinje cells (PC) in the cerebellum [ 16 ] and interneurons in the olfactory bulb [ 28 ]. In the adult nervous system, VEGF stimulates neuronal recovery from injuries after incidents, such as strokes or status epilepticus [ 29 , 30 , 31 ], while low levels of VEGF negatively influence the survival of PC [ 32 ] and neuronal injury outcome [ 33 ].…”

Section: Introductionmentioning

confidence: 99%

Disabling VEGF-Response of Purkinje Cells by Downregulation of KDR via miRNA-204-5p

Gehmeyr

Maghnouj

Tjaden

et al. 2021

IJMS

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The vascular endothelial growth factor (VEGF) is well known for its wide-ranging functions, not only in the vascular system, but also in the central (CNS) and peripheral nervous system (PNS). To study the role of VEGF in neuronal protection, growth and maturation processes have recently attracted much interest. These effects are mainly mediated by VEGF receptor 2 (VEGFR-2). Current studies have shown the age-dependent expression of VEGFR-2 in Purkinje cells (PC), promoting dendritogenesis in neonatal, but not in mature stages. We hypothesize that microRNAs (miRNA/miR) might be involved in the regulation of VEGFR-2 expression during the development of PC. In preliminary studies, we performed a miRNA profiling and identified miR204-5p as a potential regulator of VEGFR-2 expression. In the recent study, organotypic slice cultures of rat cerebella (postnatal day (p) 1 and 9) were cultivated and VEGFR-2 expression in PC was verified via immunohistochemistry. Additionally, PC at age p9 and p30 were isolated from cryosections by laser microdissection (LMD) to analyse VEGFR-2 expression by quantitative RT-PCR. To investigate the influence of miR204-5p on VEGFR-2 levels in PC, synthetic constructs including short hairpin (sh)-miR204-5p cassettes (miRNA-mimics), were microinjected into PC. The effects were analysed by confocal laser scanning microscopy (CLSM) and morphometric analysis. For the first time, we could show that miR204-5p has a negative effect on VEGF sensitivity in juvenile PC, resulting in a significant decrease of dendritic growth compared to untreated juvenile PC. In mature PC, the overexpression of miR204-5p leads to a shrinkage of dendrites despite VEGF treatment. The results of this study illustrate, for the first time, which miR204-5p expression has the potential to play a key role in cerebellar development by inhibiting VEGFR-2 expression in PC.

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Morphological Plasticity of Emerging Purkinje Cells in Response to Exogenous VEGF

Cited by 14 publications

References 80 publications

The expression of circadian clock genes in Daphnia magna diapause

The expression of circadian clock genes in Daphnia magna diapause

Progesterone Effects in the Nervous System

Disabling VEGF-Response of Purkinje Cells by Downregulation of KDR via miRNA-204-5p

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