Nardilysin regulates axonal maturation and myelination in the central and peripheral nervous system

Ohno, Mikiko; Hiraoka, Yutaka; Matsuoka, Toshihiro; Tomimoto, Hidekazu; Takao, Keizo; Miyakawa, Tsuyoshi; Oshima, Naoko; Kanazawa, Hiroshi; Kimura, Takeshi; Kita, Toru; Nishi, Eiichiro

doi:10.1038/nn.2438

Cited by 75 publications

(111 citation statements)

References 40 publications

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“…We have obtained a large set of raw data of more than 1200 mice, and have reported the data for the T-maze performance in several strains of mutant mice 3,[16][17][18][19][20][21][22] . The data of strains already published in the research article are included in the "Mouse Behavioral Phenotype Database" as a public database (URL: http://www.mousephenotype.org/).…”

Section: Representative Resultsmentioning

confidence: 99%

T-maze Forced Alternation and Left-right Discrimination Tasks for Assessing Working and Reference Memory in Mice

Shoji

Hagihara

Takao

et al. 2012

JoVE

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Forced alternation and left-right discrimination tasks using the T-maze have been widely used to assess working and reference memory, respectively, in rodents. In our laboratory, we evaluated the two types of memory in more than 30 strains of genetically engineered mice using the automated version of this apparatus. Here, we present the modified T-maze apparatus operated by a computer with a video-tracking system and our protocols in a movie format. The T-maze apparatus consists of runways partitioned off by sliding doors that can automatically open downward, each with a start box, a T-shaped alley, two boxes with automatic pellet dispensers at one side of the box, and two L-shaped alleys. Each L-shaped alley is connected to the start box so that mice can return to the start box, which excludes the effects of experimenter handling on mouse behavior. This apparatus also has an advantage that in vivo microdialysis, in vivo electrophysiology, and optogenetics techniques can be performed during T-maze performance because the doors are designed to go down into the floor. In this movie article, we describe T-maze tasks using the automated apparatus and the T-maze performance of α-CaMKII+/-mice, which are reported to show working memory deficits in the eight-arm radial maze task. Our data indicated that α-CaMKII+/-mice showed a working memory deficit, but no impairment of reference memory, and are consistent with previous findings using the eight-arm radial maze task, which supports the validity of our protocol. In addition, our data indicate that mutants tended to exhibit reversal learning deficits, suggesting that α-CaMKII deficiency causes reduced behavioral flexibility. Thus, the T-maze test using the modified automatic apparatus is useful for assessing working and reference memory and behavioral flexibility in mice.

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Section: Representative Resultsmentioning

confidence: 99%

T-maze Forced Alternation and Left-right Discrimination Tasks for Assessing Working and Reference Memory in Mice

Shoji

Hagihara

Takao

et al. 2012

JoVE

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“…BACE-1 and TACE is positively regulated by nardilysin (NRDc) [22][23][24][25][26][27][28]. BACE-1 and TACE are known to cleave NRG1 type III at distinct cleavage sites and, interestingly, BACE-1 positively regulates myelination and TACE negatively regulates myelination [25][26][27]29].…”

Section: Nrgs and The Pnsmentioning

confidence: 99%

The Role of Neuregulin-1 In the Response To Nerve Injury

Fricker

Bennett

2011

Future Neurol.

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Axons and Schwann cells exist in a highly interdependent relationship: damage to one cell type invariably leads to pathophysiological changes in the other. Greater understanding of communication between these cell types will not only give insight into peripheral nerve development, but also the reaction to and recovery from peripheral nerve injury. The type III isoform of neuregulin-1 (NRG1) has emerged as a key signaling factor that is expressed on axons and, through binding to erbB2/3 receptors on Schwann cells, regulates multiple phases of their development. In adulthood, NRG1 is dispensable for the maintenance of the myelin sheath; however, this factor is required for both axon regeneration and remyelination following nerve injury. The outcome of NRG1 signaling depends on interactions with other pathways within Schwann cells such as Notch, integrin and cAMP signaling. In certain circumstances, this signaling pathway may be maladaptive; for instance, direct binding of Mycobacterium leprae onto erbB2 receptors produces excessive activation and can actually promote demyelination. Attempts to modulate this pathway in order to promote nerve repair will therefore need to give consideration to the exact isoform used, as well as how it is processed and the context in which it is presented to the Schwann cell. Keywordsneuregulin-1; neuropathy; peripheral nerve injury; regeneration; remyelination; repair; Schwann cell Peripheral nerve injury causes significant morbidity and reduced quality of life as a consequence of weakness, sensory loss and neuropathic pain. In total, 6% of the elderly population suffer from peripheral neuropathy [1], which can be caused by metabolic diseases such as diabetes, inherited genetic disorders such as Charcot-Marie-Tooth disease, infectious and inflammatory disorders including Guillan-Barré syndrome and traumatic injury to the nerve (which alone effects up to 300,000 people in Europe per year [1,2]). In contrast to the CNS, peripheral nerves have a significant regenerative capacity [3]; however, in patients, regeneration and the clinical outcome are often poor. Axons regenerate at a rate of approximately 1 mm per day, depending on the site of the lesion. There may be a delay of months if not years before the target zone is re-innervated, and by this time, the target organ and supporting cells may have irreversibly changed, becoming much less receptive to reinnervation. The current approaches to peripheral nerve repair following nerve transection are either to surgically suture the nerve or to bridge the gap between the two cut ends. Financial & competing interests disclosureThe authors have no other rel evant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. Europe PMC Funders Group NRGs & the PNSNRGs Neuregulins are a family of growth factors en...

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“…The generation of Nrdc -/-mice with a C57BL/6 background was as previously described (13). To generate mice overexpressing murine Nrdc under the control of the Villin promoter, the Nrdc transgene consisting of the murine Nrdc cDNA downstream of the mouse Villin promoter was microinjected into fertilized C57BL/6 mouse eggs, and 2 lines were established from 4 founders.…”

Section: Methodsmentioning

confidence: 99%

“…Although NRDC is a soluble cytosolic protein with no apparent signal peptide, a portion of NRDC is secreted through an unconventional secretory pathway and distributed on the cell surface (7)(8)(9). We originally identified NRDC as a cell-surface receptor for heparin-binding epidermal growth factor-like growth factor (HB-EGF) (8), and our subsequent studies have demonstrated that NRDC enhances ectodomain shedding of multiple membrane proteins including HB-EGF (10)(11)(12)(13)(14). For instance, forced expression of NRDC or administration of the NRDC protein enhances ectodomain shedding of TNF-α through the activation of a disintegrin and metalloproteinase 17 (ADAM17) (12).…”

Section: Introductionmentioning

confidence: 99%

Nardilysin controls intestinal tumorigenesis through HDAC1/p53–dependent transcriptional regulation

Kanda¹,

Sakamoto

Matsumoto³

et al. 2018

JCI Insight

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Nardilysin regulates axonal maturation and myelination in the central and peripheral nervous system

Cited by 75 publications

References 40 publications

T-maze Forced Alternation and Left-right Discrimination Tasks for Assessing Working and Reference Memory in Mice

T-maze Forced Alternation and Left-right Discrimination Tasks for Assessing Working and Reference Memory in Mice

The Role of Neuregulin-1 In the Response To Nerve Injury

Nardilysin controls intestinal tumorigenesis through HDAC1/p53–dependent transcriptional regulation

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