Deficits in developmental neurogenesis and dendritic spine maturation in mice lacking the serine protease inhibitor neuroserpin

Hermann, Melanie; Reumann, Rebecca; Kement, Dilara; Gelderblom, Mathias; Bernreuther, Christian; Frischknecht, Renato; Schipanski, Angela; Marik, Sergej; Krasemann, Susanne; Sepulveda‐Falla, Diego; Schweizer, Michaela; Magnus, Tim; Glatzel, Markus; Galliciotti, Giovanna

doi:10.1016/j.mcn.2019.103420

Cited by 16 publications

(12 citation statements)

References 48 publications

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“…Low level of ACAN mRNA in undifferentiated cultures was previously shown in ADSCs, and in human MSCs from either umbilical cord blood (UCB-MSCs) or bone-marrow (BM-MSCs) ( Mwale et al, 2006a , b ; Guasti et al, 2012 ; Gomez-Leduc et al, 2016 ). This is not surprising, as ACAN is detected in several tissues, including in the brain parenchyma, and not restricted to mature cartilage ( Hering et al, 2020 ; Hermann et al, 2020 ; Mitlohner et al, 2020 ). Also, RUNX2 expression was previously shown in undifferentiated hBM-MSCs ( Mwale et al, 2006a ).…”

Section: Discussionmentioning

confidence: 89%

Modeling Normal and Pathological Ear Cartilage in vitro Using Somatic Stem Cells in Three-Dimensional Culture

Zucchelli

Birchall

Bulstrode

et al. 2020

Front. Cell Dev. Biol.

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Section: Discussionmentioning

confidence: 89%

Modeling Normal and Pathological Ear Cartilage in vitro Using Somatic Stem Cells in Three-Dimensional Culture

Zucchelli

Birchall

Bulstrode

et al. 2020

Front. Cell Dev. Biol.

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“…These findings raised the possibility that neuroserpin could play a general role in neuronal maturation during development, while in the mature brain its function could be more restricted to specific processes. However, the analyses of neuroserpin expression conducted so far, which have excluded its synthesis by non-neuronal cells of the nervous system [ 11 , 12 , 17 ], have not detected the presence of neuroserpin in a particular neuronal subtype. Instead, it was found in several classes of glutamatergic pyramidal neurons as well as GABA-ergic interneurons, suggesting a pan-neuronal expression that disagrees with the assignment of a role in a specific type of neuron [ 11 , 13 , 18 ].…”

Section: Identification and Tissue Expression Of Neuroserpinmentioning

confidence: 99%

“…A high perinatal expression throughout the developing nervous system supports a role for neuroserpin in late developmental processes involving neuronal differentiation, synaptogenesis and refinement of synaptic connections. The absence of neuroserpin during brain formation in knock-out mice resulted in deficient neurogenesis, with reduced proliferation of neuronal precursors in the granular cell layer of the dentate gyrus [ 17 ]. This was accompanied by early neuronal differentiation and resulted in decreased cellularity of the adult dentate gyrus, demonstrating a key role for neuroserpin in regulating the formation of the hippocampus.…”

Section: Physiological Roles Of Neuroserpinmentioning

confidence: 99%

Neuroserpin: structure, function, physiology and pathology

D'Acunto

Fra

Visentin

et al. 2021

Cell. Mol. Life Sci.

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Neuroserpin is a serine protease inhibitor identified in a search for proteins implicated in neuronal axon growth and synapse formation. Since its discovery over 30 years ago, it has been the focus of active research. Many efforts have concentrated in elucidating its neuroprotective role in brain ischemic lesions, the structural bases of neuroserpin conformational change and the effects of neuroserpin polymers that underlie the neurodegenerative disease FENIB (familial encephalopathy with neuroserpin inclusion bodies), but the investigation of the physiological roles of neuroserpin has increased over the last years. In this review, we present an updated and critical revision of the current literature dealing with neuroserpin, covering all aspects of research including the expression and physiological roles of neuroserpin, both inside and outside the nervous system; its inhibitory and non-inhibitory mechanisms of action; the molecular structure of the monomeric and polymeric conformations of neuroserpin, including a detailed description of the polymerisation mechanism; and the involvement of neuroserpin in human disease, with particular emphasis on FENIB. Finally, we briefly discuss the identification by genome-wide screening of novel neuroserpin variants and their possible pathogenicity.

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“…The correct balance between NSC proliferation and differentiation is essential for the development of brain [13][14] . The hippocampal dentate gyrus (DG) is one of the most important neurogenesis regions other than the subventricular zone (SVZ), which plays a critical role in the formation of hippocampus-dependent spatial learning and memory function [15][16] . In recent years, the effect of general anesthetics on developmental neurogenesis has been highly concerned by researchers [17] .…”

Section: Introductionmentioning

confidence: 99%

Neonatal Anesthesia by Ketamine in Rats Interferes with Proliferation and Differentiation of Hippocampal Neural Stem Cells and Neurocognitive Function in Adulthood via Inhibition of Notch1 Signalling Pathway

He¹,

Zhao²,

Hu³

et al. 2021

Preprint

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Objective: The proliferation and differentiation of developing neural stem cells (NSCs) have been particularly interesting targets to study ketamine-induced neurotoxicity. Our previous findings have shown that neonatal ketamine exposure inhibits the proliferation of NSCs in the hippocampal dentate gyrus (DG) and promotes neuronal differentiation. However, the potential mechanisms are poorly understood. Notch signalling pathway plays an important role in the regulation of neurogenesis. The objective of this study was to investigate whether Notch signalling pathway was involved in neurogenesis impairment and long-term neurocognitive dysfunction caused by neonatal ketamine exposure. Methods: Postnatal day 7 (PND-7) male Sprague-Dawley (SD) rats were intraperitoneally injected with normal saline (NS) or 40 mg/kg ketamine for four consecutive times (40 mg/kg×4) at an interval of 1 h. Notch ligand Jagged1 (0.5 mg/kg) was micro-injected into the hippocampal DG with the stereotactic apparatus at 1 h before NS or ketamine administration. Lentivirus over-expressing Notch1 intracellular domain (LV-NICD1) was micro-injected into the hippocampal DG 4 days before NS or ketamine administration. Western blot was used to detect the changes of Notch1 signalling pathway related proteins in the hippocampal DG at 24 h after administration. The S-phase marker 5-bromodeoxyuridine (BrdU) was administered immediately after the treatment, then the proliferation and differentiation of NSCs in hippocampal DG were detected by using double-immunofluorescence staining at 24 h after treatment. Moreover, the changes of hippocampus-dependent spatial memory in the adult rats were tested by Morris water maze test in 2-month-old rats. Results: Ketamine anesthesia in neonatal rats decreased the expression levels of Jagged1, Notch1, Notch1 intracellular domain (NICD1) and hairy enhancer of split 1 (Hes1), and inhibited the proliferation and astrocytic differentiation of NSCs and promoted neuronal differentiation. Neonatal ketamine exposure induced the deficit in hippocampus-dependent spatial reference memory tasks in 2-month-old rats. The micro-injection of Jagged1 or LV-NICD1 reversed the inhibitory effect of ketamine on the expression of Notch1 related proteins in the hippocampal DG, and attenuated the ketamine-induced interference of NSCs proliferation and differentiation. In addition, Morris water maze test suggested that the administration of Jagged1 or LV-NICD1 could improve cognitive function in 2-month-old rats after neonatal ketamine exposure. Conclusions: These results suggest that neonatal exposure to ketamine in rats interferes with the proliferation and differentiation of hippocampal NSCs and impairs neurocognitive function in adulthood via inhibition of Notch1 signalling pathway. These findings contribute to further understanding of the neonatal neurotoxicity induced by ketamine and its underlying mechanisms.

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Deficits in developmental neurogenesis and dendritic spine maturation in mice lacking the serine protease inhibitor neuroserpin

Cited by 16 publications

References 48 publications

Modeling Normal and Pathological Ear Cartilage in vitro Using Somatic Stem Cells in Three-Dimensional Culture

Modeling Normal and Pathological Ear Cartilage in vitro Using Somatic Stem Cells in Three-Dimensional Culture

Neuroserpin: structure, function, physiology and pathology

Neonatal Anesthesia by Ketamine in Rats Interferes with Proliferation and Differentiation of Hippocampal Neural Stem Cells and Neurocognitive Function in Adulthood via Inhibition of Notch1 Signalling Pathway

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