scholarly journals In vivo growth factor expansion of endogenous subependymal neural precursor cell populations in the adult mouse brain

1996 ◽  
Vol 16 (8) ◽  
pp. 2649-2658 ◽  
Author(s):  
CG Craig ◽  
V Tropepe ◽  
CM Morshead ◽  
BA Reynolds ◽  
S Weiss ◽  
...  
2018 ◽  
Vol 29 (10) ◽  
pp. 4381-4397 ◽  
Author(s):  
Jing Zhao ◽  
Chanel J Taylor ◽  
Estella A Newcombe ◽  
Mark D Spanevello ◽  
Imogen O’Keeffe ◽  
...  

Abstract The hippocampal dentate gyrus (DG) is a major region of the adult rodent brain in which neurogenesis occurs throughout life. The EphA4 receptor, which regulates neurogenesis and boundary formation in the developing brain, is also expressed in the adult DG, but whether it regulates adult hippocampal neurogenesis is not known. Here, we show that, in the adult mouse brain, EphA4 inhibits hippocampal precursor cell proliferation but does not affect precursor differentiation or survival. Genetic deletion or pharmacological inhibition of EphA4 significantly increased hippocampal precursor proliferation in vivo and in vitro, by blocking EphA4 forward signaling. EphA4 was expressed by mature hippocampal DG neurons but not neural precursor cells, and an EphA4 antagonist, EphA4-Fc, did not activate clonal cultures of precursors until they were co-cultured with non-precursor cells, indicating an indirect effect of EphA4 on the regulation of precursor activity. Supplementation with d-serine blocked the increased precursor proliferation induced by EphA4 inhibition, whereas blocking the interaction between d-serine and N-methyl-d-aspartate receptors (NMDARs) promoted precursor activity, even at the clonal level. Collectively, these findings demonstrate that EphA4 indirectly regulates adult hippocampal precursor proliferation and thus plays a role in neurogenesis via d-serine-regulated NMDAR signaling.


2002 ◽  
Vol 22 (5) ◽  
pp. 586-595 ◽  
Author(s):  
Karin Pierre ◽  
Pierre J. Magistretti ◽  
Luc Pellerin

Although previous Northern blot and in situ hybridization studies suggested that neurons express the monocarboxylate transporter MCT2, subsequent immunohistochemical analyzes either failed to confirm the presence of this transporter or revealed only a low density of immunolabeled neuronal processes in vivo. The authors report that appropriate section pretreatment (brief warming episode or proteinase K exposure) leads to extensive labeling of the neuropil, which appears as tiny puncta throughout the whole mouse brain. In addition, intense MCT2 immunoreactivity was found in cerebellar Purkinje cell bodies and their processes, on mossy fibers in the cerebellum, and on sensory fibers in the brainstem. Double immunofluorescent labeling with appropriate markers and observation with epifluorescence and confocal microscopy did not show extensive colocalization of MCT2 immunoreactivity with presynaptic or postsynaptic elements, but colocalization could be observed occasionally in the cortex with the postsynaptic density protein PSD95. Observations made at the electron microscopic level in the cortex corroborated these results and showed that MCT2 immunoreactivity was associated with wide membrane segments of neuronal processes. These data provide convincing evidence that MCT2 represents a major neuronal monocarboxylate transporter in the adult mouse brain, and further suggest that mature neurons could use monocarboxylates such as lactate as additional energy substrates.


2010 ◽  
Vol 18 (6) ◽  
pp. 1183-1191 ◽  
Author(s):  
Jochen De Vry ◽  
Pilar Martínez-Martínez ◽  
Mario Losen ◽  
Gerard H Bode ◽  
Yasin Temel ◽  
...  

2007 ◽  
Vol 85 (13) ◽  
pp. 2981-2990 ◽  
Author(s):  
Gui-Ping Han ◽  
Li Li ◽  
Isao Kosugi ◽  
Hideya Kawasaki ◽  
Takashi Tsuchida ◽  
...  

1999 ◽  
Vol 252 (1) ◽  
pp. 75-95 ◽  
Author(s):  
Scott R. Whittemore ◽  
Dante J. Morassutti ◽  
Winston M. Walters ◽  
Rong-Huan Liu ◽  
David S.K. Magnuson

2005 ◽  
Vol 386 (3) ◽  
pp. 461-470 ◽  
Author(s):  
Go KURATOMI ◽  
Akiyoshi KOMURO ◽  
Kouichiro GOTO ◽  
Masahiko SHINOZAKI ◽  
Keiji MIYAZAWA ◽  
...  

Inhibitory Smad, Smad7, is a potent inhibitor of TGF-β (transforming growth factor-β) superfamily signalling. By binding to activated type I receptors, it prevents the activation of R-Smads (receptor-regulated Smads). To identify new components of the Smad pathway, we performed yeast two-hybrid screening using Smad7 as bait, and identified NEDD4-2 (neural precursor cell expressed, developmentally down-regulated 4-2) as a direct binding partner of Smad7. NEDD4-2 is structurally similar to Smurfs (Smad ubiquitin regulatory factors) 1 and 2, which were identified previously as E3 ubiquitin ligases for R-Smads and TGF-β superfamily receptors. NEDD4-2 functions like Smurfs 1 and 2 in that it associates with TGF-β type I receptor via Smad7, and induces its ubiquitin-dependent degradation. Moreover, NEDD4-2 bound to TGF-β-specific R-Smads, Smads 2 and 3, in a ligand-dependent manner, and induced degradation of Smad2, but not Smad3. However, in contrast with Smurf2, NEDD4-2 failed to induce ubiquitination of SnoN (Ski-related novel protein N), although NEDD4-2 bound to SnoN via Smad2 more strongly than Smurf2. We showed further that overexpressed NEDD4-2 prevents transcriptional activity induced by TGF-β and BMP, whereas silencing of the NEDD4-2 gene by siRNA (small interfering RNA) resulted in enhancement of the responsiveness to TGF-β superfamily cytokines. These data suggest that NEDD4-2 is a member of the Smurf-like C2-WW-HECT (WW is Trp-Trp and HECT is homologous to the E6-accessory protein) type E3 ubiquitin ligases, which negatively regulate TGF-β superfamily signalling through similar, but not identical, mechanisms to those used by Smurfs.


FEBS Letters ◽  
2004 ◽  
Vol 569 (1-3) ◽  
pp. 293-300 ◽  
Author(s):  
Ruijin Shao ◽  
Fu-Ping Zhang ◽  
Fei Tian ◽  
P Anders Friberg ◽  
Xiaoyang Wang ◽  
...  

Science ◽  
1979 ◽  
Vol 204 (4391) ◽  
pp. 427-429 ◽  
Author(s):  
P Walker ◽  
M. Weichsel ◽  
D. Fisher ◽  
S. Guo ◽  
D. Fisher

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