scholarly journals Diet-induced obesity has neuroprotective effects in murine gastric enteric nervous system: involvement of leptin and glial cell line-derived neurotrophic factor

2012 ◽  
Vol 590 (3) ◽  
pp. 533-544 ◽  
Author(s):  
Charlotte Baudry ◽  
François Reichardt ◽  
Justine Marchix ◽  
André Bado ◽  
Michael Schemann ◽  
...  
2007 ◽  
Vol 293 (2) ◽  
pp. G461-G468 ◽  
Author(s):  
Sean C. McDonagh ◽  
Jenny Lee ◽  
Angelo Izzo ◽  
Patricia L. Brubaker

The intestinal glucagon-like peptides GLP-1 and GLP-2 inhibit intestinal motility, whereas GLP-2 also stimulates growth of the intestinal mucosa. However, the mechanisms of action of these peptides in the intestine remain poorly characterized. To determine the role of the enteric nervous system in the actions of GLP-1 and GLP-2 on the intestine, the glial cell line-derived neurotropic factor family receptor α2 (GFRα2) knockout (KO) mouse was employed. The mice exhibited decreased cholinergic staining, as well as reduced mRNA transcripts for substance P-ergic excitatory motoneurons in the enteric nervous system (ENS) ( P < 0.05). Examination of parameters of intestinal growth (including small and large intestinal weight and small intestinal villus height, crypt depth, and crypt cell proliferation) demonstrated no differences between wild-type and KO mice in either basal or GLP-2-stimulated mucosal growth. Nonetheless, KO mice exhibited reduced numbers of synaptophysin-positive enteroendocrine cells ( P < 0.05), as well as a markedly impaired basal gastrointestinal (GI) transit rate ( P < 0.05). Furthermore, acute administration of GLP-1 and GLP-2 significantly inhibited transit rates in wild-type mice ( P < 0.05–0.01) but had no effect in GFRα2 KO mice. Despite these changes, expression of mRNA transcripts for the GLP receptors was not reduced in the ENS of KO animals, suggesting that GLP-1 and -2 modulate intestinal transit through enhancement of inhibitory input to cholinergic/substance P-ergic excitatory motoneurons. Together, these findings demonstrate a role for GFRα2-expressing enteric neurons in the downstream signaling of the glucagon-like peptides to inhibit GI motility, but not in intestinal growth.


2005 ◽  
Vol 102 (1) ◽  
pp. 80-89 ◽  
Author(s):  
Takao Yasuhara ◽  
Tetsuro Shingo ◽  
Kenichiro Muraoka ◽  
Kazuki Kobayashi ◽  
Akira Takeuchi ◽  
...  

Object. Glial cell line—derived neurotrophic factor (GDNF) has been shown to confer neuroprotective effects on dopaminergic neurons. The authors investigated the effects of GDNF on 6-hydroxydopamine (6-OHDA)—treated dopaminergic neurons in vitro and in vivo. Methods. First, the authors examined how 1, 10, or 100 ng/ml of GDNF, administered to cells 24 hours before, simultaneously with, or 2 or 4 hours after 6-OHDA was added, affected dopaminergic neurons. In a primary culture of E14 murine ventral mesencephalic neurons, earlier treatment with the higher dosage of GDNF suppressed 6-OHDA—induced loss of dopaminergic neurons better than later treatment. Next, the authors examined whether continuous infusion of GDNF at earlier time points would demonstrate a greater neuroprotective effect in a rat model of Parkinson disease (PD). They established a human GDNF-secreting cell line, called BHK-GDNF, and encapsulated the cells into hollow fibers. The encapsulated cells were unilaterally implanted into the striatum of adult rats 1 week before; simultaneously with; or 1, 2, or 4 weeks after 6-OHDA was given to induce lesions of the same striatum. With the earlier transplantation of a BHK-GDNF capsule, there was a significant reduction in the number of amphetamine-induced rotations displayed by the animals. Rats that had received earlier implantation of BHK-GDNF capsules displayed more tyrosine hydroxylase—positive neurons in the substantia nigra pars compacta and a tendency for glial proliferation in the striatum. Conclusions. These neuroprotective effects may be related to glial proliferation and signaling via the GDNF receptor α1. The results of this study support a role for this grafting technique in the treatment of PD.


2015 ◽  
Vol 7 (4) ◽  
pp. 211-220 ◽  
Author(s):  
T.V. Shishkina ◽  
M.V. Vedunova ◽  
T.A. Mishchenko ◽  
I.V. Mukhina

2011 ◽  
Vol 140 (5) ◽  
pp. S-44
Author(s):  
Simon M. Mwangi ◽  
Smitha Marri ◽  
Behtash G. Nezami ◽  
Ping P. Fu ◽  
Javelin C. Cheng ◽  
...  

Neuroscience ◽  
2003 ◽  
Vol 121 (4) ◽  
pp. 899-906 ◽  
Author(s):  
Y Shimoyama ◽  
Y Morikawa ◽  
M Ichihara ◽  
Y Kodama ◽  
N Fukuda ◽  
...  

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