Effect of retinoic acid on limb regeneration in Xenopus laevis

1983 ◽  
Vol 61 (12) ◽  
pp. 2698-2702 ◽  
Author(s):  
Steven R. Scadding

The objective of this experiment was to determine the effect of retinoic acid on the process of limb regeneration in the African clawed frog, Xenopus laevis. Limbs were bilaterally amputated through the radio-ulna and then treated for 15 days with retinoic acid in the aquarium water, at 3, 15, or 75 IU/mL. The retinoic acid inhibited limb regeneration in a dose-dependent manner, reduced the length of the regenerates, and produced irregularities in the morphogenesis of the cartilage rod in the regenerate. The regenerated limbs were removed after 150 days by amputation through the humerus, and the limbs were again allowed to regenerate. In the retinoic acid treated animals, despite the fact that retinoic acid treatment had been discontinued over 4 months previously, limb regeneration was still inhibited. These results suggest that retinoic acid has a long-term effect on the treated animals.


2017 ◽  
Vol 95 (9) ◽  
pp. 653-661 ◽  
Author(s):  
C.D. Rand ◽  
G.E. Spencer ◽  
R.L. Carlone

Retinoic acid (RA), an active metabolite of vitamin A, is important for neural development and regeneration and can induce neurite outgrowth. It may also act as a guidance molecule by attracting neurite processes during outgrowth. In the African Clawed Frog (Xenopus laevis (Daudin, 1802)), RA has been shown to play an important role in the development of the anterior–posterior axis. However, whether RA can act as a trophic or tropic molecule on embryonic neurons of this species has not been determined. In this study, we investigated the effects of two retinoid isomers, all-trans retinoic acid (atRA) and 9-cis retinoic acid (9-cisRA), on cultured embryonic spinal cord neurons of X. laevis. Both isomers significantly enhanced neurite outgrowth compared with the vehicle control. In addition, atRA induced growth cone turning, which was blocked with a retinoic acid receptor (RAR) antagonist, selective for the β receptor subtype. Immunostaining also revealed RAR immunoreactivity in the neurites and growth cones of these cells. Interestingly, the 9-cisRA isomer also induced significant growth cone turning and this response was inhibited by a retinoid X receptor (RXR) pan-antagonist. Overall, we have provided evidence for both trophic and chemotropic actions of two naturally occurring retinoid isomers on Xenopus embryonic spinal cord neurons in culture.



1993 ◽  
Vol 71 (5-6) ◽  
pp. 321-325 ◽  
Author(s):  
Morikuni Takigawa ◽  
Hiroshi Maeda ◽  
Kenichi Ueyama ◽  
Hidefumi Tominaga ◽  
Kei Matsumoto

The effect of long-term methamphetamine (MAP) treatment on intracranial self-stimulation of the lateral hypotholamus and locomotor traces was assessed. An attempt was made to provide a useful animal model for understanding anhedonia, stereotypy, and reoccurrence of liability, which are analogous to symptoms of schizophrenia. The frequency of intracranial self-stimulation (ICSS) as used as a measure of the animals' "hedonic–anhedonic" state. Following long-term MAP treatment (3 mg/kg), rats gradually showed stereotyped behavior, and became inactive and unresponsive to ICSS. These behavioral changes and decreased ICSS lasted several weeks after cessation of chronic MAP treatment and seemed to suggest post-MAP chronic psychosis and (or) anhedonia, two of the negative symptoms of schizophrenia. The traces of rat behavior affected by chronic MAP treatment were classified into three types, peripheral, mixed, and fixed, occurring in a dose-dependent manner. Reverse tolerance, similar to the reoccurrence of schizophrenic symptoms, was observed as a fixed stereotypy associated with loss of ICSS. These abnormal phenomena were suppressed by pretreatment with haloperidol. In the present study, the combination of ICSS and locomotor trace affected by chronic MAP treatment was proposed as an animal model of schizophrenia and as a useful technique for gauging the effect of neuroleptics.Key words: self-stimulation, anhedonia, stereotypy, reverse tolerance, animal disease model, schizophrenia, methamphetamine.



2017 ◽  
Vol 43 (4) ◽  
pp. 1449-1459 ◽  
Author(s):  
Renata A. C. Silva ◽  
Andréa F. Gonçalves ◽  
Priscila P. dos Santos ◽  
Bruna Rafacho ◽  
Renan F. T. Claro ◽  
...  

Background/Aims: This study aimed to discern whether the cardiac alterations caused by retinoic acid (RA) in normal adult rats are physiologic or pathologic. Methods and Results: Wistar rats were assigned into four groups: control animals (C, n = 20) received a standard rat chow; animals fed a diet supplemented with 0.3 mg/kg/day all-trans-RA (AR1, n = 20); animals fed a diet supplemented with 5 mg/kg/day all-trans-RA (AR2, n = 20); and animals fed a diet supplemented with 10 mg/kg/day all-trans-RA (AR3, n = 20). After 2 months, the animals were submitted to echocardiogram, isolated heart study, histology, energy metabolism status, oxidative stress condition, and the signaling pathway involved in the cardiac remodeling induced by RA. RA increased myocyte cross-sectional area in a dose-dependent manner. The treatment did not change the morphological and functional variables, assessed by echocardiogram and isolated heart study. In contrast, RA changed catalases, superoxide dismutase, and glutathione peroxidases and was associated with increased values of lipid hydroperoxide, suggesting oxidative stress. RA also reduced citrate synthase, enzymatic mitochondrial complex II, ATP synthase, and enzymes of fatty acid metabolism and was associated with increased enzymes involved in glucose use. In addition, RA increased JNK 1/2 expression, without changes in TGF-β, PI3K, AKT, NFκB, S6K, and ERK. Conclusion: In normal rats, RA induces cardiac hypertrophy in a dose-dependent manner. The non-participation of the PI3K/Akt pathway, associated with the participation of the JNK pathway, oxidative stress, and changes in energy metabolism, suggests that cardiac remodeling induced by RA supplementation is deleterious.





2007 ◽  
Vol 292 (5) ◽  
pp. R1916-R1925 ◽  
Author(s):  
Monika Sundqvist

Little is known about the purinergic regulation of intestinal motor activity in amphibians. Purinergic control of intestinal motility is subject to changes during development in mammals. The aim of this study was to investigate purinergic control of intestinal smooth muscle in the amphibian Xenopus laevis and explore possible changes in this system during the developmental phase of metamorphosis. Effects of purinergic compounds on mean force and contraction frequency in intestinal circular muscle strips from prometamorphic, metamorphic, and juvenile animals were investigated. Before metamorphosis, low concentrations of ATP reduced motor activity, whereas the effects were reversed at higher concentrations. ATP-induced relaxation was not inhibited by the P2-receptor antagonist pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS) but was blocked by the ecto-nucleotidase inhibitor 6- N, N-diethyl-d-β,γ-dibromomethylene ATP ( ARL67256 ), indicating that an ATP-derived metabolite mediated the relaxation response at this stage. Adenosine induced relaxation before, during, and after metamorphosis, which was blocked by the A1-receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). The stable ATP-analog adenosine 5′-[γ-thio]-triphosphate (ATPγS) and 2-methylthioATP (2-MeSATP) elicited contractions in the circular muscle strips in prometamorphic tadpoles. However, in juvenile froglets, 2-MeSATP caused relaxation, as did ATPγS at low concentrations. The P2Y11/P2X1-receptor antagonist NF157 antagonized the ATPγS-induced relaxation. The P2X-preferring agonist α-β-methyleneadenosine 5′-triphosphate (α-β-MeATP) evoked PPADS-sensitive increases in mean force at all stages investigated. This study demonstrates the existence of an adenosine A1-like receptor mediating relaxation and a P2X-like receptor mediating contraction in the X. laevis gut before, during, and after metamorphosis. Furthermore, the development of a P2Y11-like receptor-mediated relaxation during metamorphosis is shown.



Blood ◽  
1997 ◽  
Vol 90 (7) ◽  
pp. 2747-2756 ◽  
Author(s):  
Richard S. Larson ◽  
David C. Brown ◽  
Larry A. Sklar

All-trans retinoic acid (tRA) is a potent differentiation agent that is effective therapy for acute promyelocytic leukemia (APL). However, 5% to 25% of patients develop retinoic acid syndrome, a potentially life-threatening complication in which the pathogenesis relates to adhesive alterations of APL cells. Therefore, we investigated the relationship between tRA-induced differentiation and the adhesive properties of APL cells. After confirming differentiation-related morphological changes of NB-4 cells in response to tRA, we showed that homotypic aggregation of NB-4 cells grown in tRA for 72 hours is dose-dependent with a median effective dose of approximately 50 nmol/L. Maximal aggregation occurred at mean and peak therapeutic serum concentrations (100 and 1,000 nmol/L, respectively). Aggregation also increased with the length of tRA exposure over 168 hours. Aggregation was inhibited by neutralizing antibodies against LFA-1 and ICAM-2. Notably, antibodies directed against VLA-4, other β2 integrins (Mac-1 and p150), or other potential LFA-1 counterstructures that were expressed on the cell surface (ICAM-1 and ICAM-3) did not block aggregation. Aggregation occurred with similar kinetics regardless of the presence of phorbol ester or the “activating” monoclonal antibody (MoAb) KIM 185, suggesting that the avidity of LFA-1 is not modulated on NB-4 cells in a manner similar to other leukocytes. Consistent with the prompt clinical effectiveness of methyl prednisolone sodium succinate (MPSS) in retinoic acid syndrome, MPSS rapidly inhibited homotypic aggregation in a dose-dependent manner. Thus, tRA alters the adhesive properties of APL cells by inducing the expression of high-avidity β2 integrins, aggregation is inhibited by LFA-1 and ICAM-2 MoAb, and tRA effects are rapidly reversible by MPSS. Taken together, our findings provide a clinically relevant system for study of LFA-1/ICAM-2 interaction and suggest a mechanism in part for retinoic acid syndrome and the effectiveness of MPSS in ameliorating retinoic acid syndrome.





2008 ◽  
Vol 23 (1) ◽  
pp. 131-144 ◽  
Author(s):  
Chun-Sik Yoon ◽  
Jung-Hyo Jin ◽  
Joo-Hung Park ◽  
Chang-Yeol Yeo ◽  
Song-Ja Kim ◽  
...  


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