scholarly journals Sleep Deprivation Effects on Growth Factor Expression in Neonatal Rats: A Potential Role for BDNF in the Mediation of Delta Power

2004 ◽  
Vol 91 (4) ◽  
pp. 1586-1595 ◽  
Author(s):  
Ilana S. Hairston ◽  
Christelle Peyron ◽  
Daniel P. Denning ◽  
Norman F. Ruby ◽  
Judith Flores ◽  
...  

The sleeping brain differs from the waking brain in its electrophysiological and molecular properties, including the expression of growth factors and immediate early genes (IEG). Sleep architecture and homeostatic regulation of sleep in neonates is distinct from that of adults. Hence, the present study addressed the question whether the unique homeostatic response to sleep deprivation in neonates is reflected in mRNA expression of the IEG cFos, brain-derived nerve growth factor (BDNF), and basic fibroblast growth factor (FGF2) in the cortex. As sleep deprivation is stressful to developing rats, we also investigated whether the increased levels of corticosterone would affect the expression of growth factors in the hippocampus, known to be sensitive to glucocorticoid levels. At postnatal days 16, 20, and 24, rats were subjected to sleep deprivation, maternal separation without sleep deprivation, sleep deprivation with 2 h recovery sleep, or no intervention. mRNA expression was quantified in the cortex and hippocampus. cFos was increased after sleep deprivation and was similar to control level after 2 h recovery sleep irrespective of age or brain region. BDNF was increased by sleep deprivation in the cortex at P20 and P24 and only at P24 in the hippocampus. FGF2 increased during recovery sleep at all ages in both brain regions. We conclude that cortical BDNF expression reflects the onset of adult sleep-homeostatic response, whereas the profile of expression of both growth factors suggests a trophic effect of mild sleep deprivation.

1999 ◽  
Vol 276 (2) ◽  
pp. R522-R529 ◽  
Author(s):  
Jennie E. Larkin ◽  
H. Craig Heller

Electroencephalographic slow-wave activity (SWA) in non-rapid eye movement (NREM) sleep is directly related to prior sleep/wake history, with high levels of SWA following extended periods of wake. Therefore, SWA has been thought to reflect the level of accumulated sleep need. The discovery that euthermic intervals between hibernation bouts are spent primarily in sleep and that this sleep is characterized by high and monotonically declining SWA has led to speculation that sleep homeostasis may play a fundamental role in the regulation of the timing of bouts of hibernation and periodic arousals to euthermia. It was proposed that because the SWA profile seen after arousal from hibernation is strikingly similar to what is seen in nonhibernating mammals after extended periods of wakefulness, that hibernating mammals may arouse from hibernation with significant accumulated sleep need. This sleep need may accumulate during hibernation because the low brain temperatures during hibernation may not be compatible with sleep restorative processes. In the present study, golden-mantled ground squirrels were sleep deprived during the first 4 h of interbout euthermia by injection of caffeine (20 mg/kg ip). We predicted that if the SWA peaks after bouts of hibernation reflected a homeostatic response to an accumulated sleep need, sleep deprivation should simply have displaced and possibly augmented the SWA to subsequent recovery sleep. Instead we found that after caffeine-induced sleep deprivation of animals just aroused from hibernation, the anticipated high SWA typical of recovery sleep did not occur. Similar results were found in a study that induced sleep deprivation by gentle handling (19). These findings indicate that the SWA peak immediately after hibernation does not represent homeostatic regulation of NREM sleep, as it normally does after prolonged wakefulness during euthermia, but instead may reflect some other neurological process in the recovery of brain function from an extended period at low temperature.


1995 ◽  
Vol 108 (6) ◽  
pp. 2153-2162 ◽  
Author(s):  
J.F. Talts ◽  
A. Weller ◽  
R. Timpl ◽  
M. Ekblom ◽  
P. Ekblom

We have here studied the composition and regulation of stromal extracellular matrix components in an experimental tumor model. Nude mice were inoculated with WCCS-1 cells, a human Wilms' tumor cell line. In the formed tumors the stroma was found to contain mesenchymal extracellular matrix proteins such as tenascin-C, fibulins-1 and 2 and fibronectin, but no nidogen. Nidogen was confined to basement membranes of tumor blood vessels. Since glucocorticoids have been shown to downregulate tenascin-C expression in vitro, we tested whether dexamethasone can influence biosynthesis of extracellular matrix components during tumor formation in vivo. A downregulation of tenascin-C mRNA and an upregulation of fibronectin mRNA expression by dexamethasone was noted. Transforming growth factor-beta 1 mRNA levels were unaffected by the dexamethasone treatment. Glucocorticoids can thus downregulate tenascin-C synthesis although local stimulatory growth factors are present. The competition between a negative and a positive extrinsic factor on synthesis of stromal extracellular matrix components was studied in a fibroblast/preadipocyte cell line. Transforming growth factor-beta 1 stimulated tenascin-C synthesis but did not affect fibronectin or fibulin-2 synthesis. Dexamethasone at high concentrations could completely suppress the effect of transforming growth factor-beta 1 on tenascin-C mRNA expression. Transforming growth factor-beta 1 could in turn overcome the downregulation of tenascin-C mRNA expression caused by a lower concentration of dexamethasone. We therefore suggest that the limited expression of tenascin-C in part is due to a continuous suppression by physiological levels of glucocorticoids, which can be overcome by local stimulatory growth factors when present in sufficient amounts.


2002 ◽  
Vol 111 (10) ◽  
pp. 947-953 ◽  
Author(s):  
Shin-Ichi Ishimoto ◽  
Toshio Ishibashi

The participation of growth factors in wound healing of tympanic membranes (TMs) is established. To determine the possible role of these growth factors in normal healing, we examined the regulation of keratinocyte growth factor (KGF), transforming growth factor–α (TGF-α), and basic fibroblast growth factor (bFGF) messenger RNA (mRNA) expression in wounded TMs of glucocorticoid-treated rats; these rats have severe wound healing abnormalities. Induction of KGF, TGF-α, and bFGF mRNA expression after TM injury was significantly reduced in these rats. Moreover, we found that the average number of bromodeoxyundine-positive cells in a glucocorticoid-treated group was significantly lower than that in controls. The data suggest that reduced expression of these genes might be partially responsible for the wound healing defects seen in these animals. These results provide a possible explanation for the beneficial effect of exogenous KGF, TGF-α, or bFGF in treatment of wound healing disorders of the TM.


2016 ◽  
Vol 6 (3) ◽  
pp. 107-119 ◽  
Author(s):  
Ashu Bhasin ◽  
M.V. Padma Srivastava ◽  
Sujata Mohanty ◽  
Sivasubramaniam Vivekanandhan ◽  
Sakshi Sharma ◽  
...  

Background: The emerging role of stem cell technology and transplantation has helped scientists to study their potential role in neural repair and regeneration. The fate of stem cells is determined by their niche, consisting of surrounding cells and the secreted trophic growth factors. This interim report evaluates the safety, feasibility and efficacy (if any) of bone marrow-derived mononuclear stem cells (BM-MNC) in chronic ischemic stroke by studying the release of serum vascular endothelial growth factor (VEGF) and brain-derived neurotrophic growth factor (BDNF). Methods: Twenty stroke patients and 20 age-matched healthy controls were recruited with the following inclusion criteria: 3 months to 1.5 years from the index event, Medical Research Council (MRC) grade of hand muscles of at least 2, Brunnstrom stage 2-5, conscious, and comprehendible. They were randomized to one group receiving autologous BM-MNC (mean 60-70 million) and to another group receiving saline infusion (placebo). All patients were administered a neuromotor rehabilitation regime for 8 weeks. Clinical assessments [Fugl Meyer scale (FM), modified Barthel index (mBI), MRC grade, Ashworth tone scale] were carried out and serum VEGF and BDNF levels were assessed at baseline and at 8 weeks. Results: No serious adverse events were observed during the study. There was no statistically significant clinical improvement between the groups (FM: 95% CI 15.2-5.35, p = 0.25; mBI: 95% CI 14.3-4.5, p = 0.31). VEGF and BDNF expression was found to be greater in group 1 compared to group 2 (VEGF: 442.1 vs. 400.3 pg/ml, p = 0.67; BDNF: 21.3 vs. 19.5 ng/ml) without any statistically significant difference. Conclusion: Autologous mononuclear stem cell infusion is safe and tolerable by chronic ischemic stroke patients. The released growth factors (VEGF and BDNF) in the microenvironment could be due to the paracrine hypothesis of stem cell niche and neurorehabilitation regime.


2010 ◽  
Vol 109 (1) ◽  
pp. 60-67 ◽  
Author(s):  
Maria R. Bonsignore ◽  
Giuseppe Morici ◽  
Roberta Riccioni ◽  
Alice Huertas ◽  
Eleonora Petrucci ◽  
...  

The effects of endurance or maximal exercise on mobilization of bone marrow-derived hemopoietic and angiogenetic progenitors in healthy subjects are poorly defined. In 10 healthy amateur runners, we collected venous blood before, at the end of, and the day after a marathon race ( n = 9), and before and at the end of a 1.5-km field test ( n = 8), and measured hemopoietic and angiogenetic progenitors by flow cytometry and culture assays, as well as plasma or serum concentrations of several cytokines/growth factors. After the marathon, CD34+ cells were unchanged, whereas clonogenetic assays showed decreased number of colonies for both erythropoietic (BFU-E) and granulocyte-monocyte (CFU-GM) series, returning to baseline the morning post-race. Conversely, CD34+ cells, BFU-E, and CFU-GM increased after the field test. Angiogenetic progenitors, assessed as CD34+KDR+ and CD133+VE-cadherin+ cells or as adherent cells in culture expressing endothelial markers, increased after both endurance and maximal exercise but showed a different pattern between protocols. Interleukin-6 increased more after the marathon than after the field test, whereas hepatocyte growth factor and stem cell factor increased similarly in both protocols. Plasma levels of angiopoietin (Ang) 1 and 2 increased after both types of exercise, whereas the Ang-1-to-Ang-2 ratio or vascular endothelial growth factor-A were little affected. These data suggest that circulating hemopoietic progenitors may be utilized in peripheral tissues during prolonged endurance exercise. Endothelial progenitor mobilization after exercise in healthy trained subjects appears modulated by the type of exercise. Exercise-induced increase in growth factors suggests a physiological trophic effect of exercise on the bone marrow.


2021 ◽  
Vol 14 (4) ◽  
pp. 1028-1037
Author(s):  
Noritaka Maeta ◽  
Katsutoshi Tamura ◽  
Fuuna Ezuka ◽  
Hiroshi Takemitsu

Background and Aim: Mesenchymal stem cells (MSCs), which have multi-lineage differentiation potentials, are a promising source for regenerative medicine. However, the focus of study of MSCs is shifting from the characterization of the differentiation potential to their secretion potential for cell transplantation. Tissue regeneration and the attenuation of immune responses are thought to be affected by the secretion of multiple growth factors and cytokines by MSCs. However, the secretion potential of MSCs profiling remains incompletely characterized. In this study, we focused on the secretion ability related and protein mRNA expression of dog adipose tissue-derived MSCs (AT-MSC), bone marrow (BM)-derived MSCs, and BM-derived mononuclear cells (BM-MNC). Materials and Methods: Real-time polymerase chain reaction analyses revealed mRNA expression of nine growth factors and seven interleukins in these types of cells and three growth factors protein expression were determined using Enzyme-linked immunosorbent assay. Results: For the BM-MNC growth factors, the mRNA expression of transforming growth factor-β (TGF-β) was the highest. For the BM-derived MSC (BM-MSC) and AT-MSC growth factors, the mRNA expression of vascular endothelial growth factor (VEGF) was highest. BM-MSCs and AT-MSCs showed similar expression profiles. In contrast, BM-MNCs showed unique expression profiles for hepatocyte growth factor and epidermal growth factor. The three types of cells showed a similar expression of TGF-β. Conclusion: We conclude that expression of cytokine proteins and mRNAs suggests involvement in tissue repair and protection.


2020 ◽  
Vol 21 (22) ◽  
pp. 8598
Author(s):  
Linna Guo ◽  
Ziang Zou ◽  
Ralf Smeets ◽  
Lan Kluwe ◽  
Philip Hartjen ◽  
...  

Ultraviolet (UV) light and non-thermal plasma (NTP) are promising chair-side surface treatment methods to overcome the time-dependent aging of dental implant surfaces. After showing the efficiency of UV light and NTP treatment in restoring the biological activity of titanium and zirconia surfaces in vitro, the objective of this study was to define appropriate processing times for clinical use. Titanium and zirconia disks were treated by UV light and non-thermal oxygen plasma with increasing duration. Non-treated disks were set as controls. Murine osteoblast-like cells (MC3T3-E1) were seeded onto the treated or non-treated disks. After 2 and 24 h of incubation, the viability of cells on surfaces was assessed using an MTS assay. mRNA expression of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) were assessed using real-time reverse transcription polymerase chain reaction analysis. Cellular morphology and attachment were observed using confocal microscopy. The viability of MC3T3-E1 was significantly increased in 12 min UV-light treated and 1 min oxygen NTP treated groups. VEGF relative expression reached the highest levels on 12 min UV-light and 1 min NTP treated surfaces of both disks. The highest levels of HGF relative expression were reached on 12 min UV light treated zirconia surfaces. However, cells on 12 and 16 min UV-light and NTP treated surfaces of both materials had a more widely spread cytoskeleton compared to control groups. Twelve min UV-light and one min non-thermal oxygen plasma treatment on titanium and zirconia may be the favored times in terms of increasing the viability, mRNA expression of growth factors and cellular attachment in MC3T3-E1 cells.


2019 ◽  
Vol 20 (8) ◽  
pp. 1859 ◽  
Author(s):  
Phil June Park ◽  
Eun-Gyung Cho

Adiponectin (APN), released mainly from adipose tissue, is a well-known homeostatic factor for regulating glucose levels, lipid metabolism, and insulin sensitivity. A recent study showed that human hair follicles express APN receptors and the presence of APN-mediated hair growth signaling, thereby suggesting that APN is a potent hair growth-promoting adipokine. Previously, kojyl cinnamate ester derivatives (KCEDs) were synthesized in our institute as new anti-aging or adiponectin-/adipogenesis-inducing compounds. Here, we tested the activity of these derivatives to induce endogenous APN secretion. Among the derivatives, KCED-1 and KCED-2 showed improved activity in inducing APN mRNA expression, secretion of APN protein, and adipogenesis in human subcutaneous fat cells (hSCFs) when compared with the effects of Seletinoid G, a verified APN inducer. When human follicular dermal papilla cells were treated with the culture supernatant of KCED-1- or KCED-2-treated hSCFs, the mRNA expression of APN-induced hair growth factors such as insulin-like growth factor, hepatocyte growth factor, and vascular endothelial growth factor was upregulated compared with that in the control. Taken together, our study shows that among kojyl cinnamate ester derivatives, KCED-1, KCED-2, as well as Seletinoid G are effective inducers of endogenous APN production in subcutaneous fat tissues, which may in turn contribute to the promotion of hair growth in the human scalp.


2011 ◽  
Vol 300 (2) ◽  
pp. H431-H439 ◽  
Author(s):  
Toshiaki Mishima ◽  
Yoshiya Ito ◽  
Kanako Hosono ◽  
Yukio Tamura ◽  
Yasushi Uchida ◽  
...  

It is known that the neural system plays a fundamental role in neovascularization. A neuropeptide, calcitonin gene-related peptide (CGRP), is widely distributed in the central and peripheral neuronal systems. However, it remains to be elucidated the role of CGRP in angiogenesis during ischemia. The present study examined whether endogenous CGRP released from neuronal systems facilitates revascularization in response to ischemia using CGRP knockout mice (CGRP−/−). CGRP−/− or their wild-type littermates (CGRP+/+) were subjected to unilateral hindlimb ischemia. CGRP−/− exhibited impaired blood flow recovery from ischemia and decreased capillary density expressed in terms of the number of CD-31-positive cells in the ischemic tissues compared with CGRP+/+. In vivo microscopic studies showed that the functional capillary density in CGRP−/− was reduced. Hindlimb ischemia increased the expression of pro-CGRP mRNA and of CGRP protein in the lumbar dorsal root ganglia. Lack of CGRP decreased mRNA expression of growth factors, including CD31, vascular endothelial growth factor-A, basic fibroblast growth factor, and transforming growth factor-β, in the ischemic limb tissue. The application of CGRP enhanced the mRNA expression of CD31 and VEGF-A in human umbilical vein endothelial cells (HUVECs) and fibroblasts. Subcutaneous infusion of CGRP8–37, a CGRP antagonist, using miniosmotic pumps delayed angiogenesis and reduced the expression of proangiogenic growth factors during hindlimb ischemia. These results indicate that endogenous CGRP facilitates angiogenesis in response to ischemia. Targeting CGRP may provide a promising approach for controlling angiogenesis related to pathophysiological conditions.


1998 ◽  
Vol 21 (3) ◽  
pp. 355-362 ◽  
Author(s):  
RK Srivastava ◽  
Y Gu ◽  
S Ayloo ◽  
M Zilberstein ◽  
G Gibori

During pregnancy, the decidua is comprised of two separate tissues located either mesometrially or antimesometrially in the uterus. Trophoblast invasion takes place only in the mesometrial decidua, where extensive angiogenesis, essential for successful implantation, occurs. Both basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) have been implicated in this phenomenon. The aim of this study was to determine whether the expression of both growth factors is intrinsic to decidua and occurs in the absence of conceptuses, whether their genes are expressed specifically in the mesometrial decidua, the site of angiogenesis, and whether both growth factors are developmentally and hormonally regulated. Decidual tissue was dissected from pseudopregnant rats and levels of both bFGF and VEGF mRNA were examined in mesometrial and antimesometrial decidua by semi-quantitative RT-PCR at different stages of pseudopregnancy. Although induction of decidualization triggered the mRNA expression of bFGF, VEGF mRNA expression remained unchanged. VEGF mRNA level was similar in both antimesometrial and mesometrial decidua, and remained constant throughout pseudopregnancy. In sharp contrast, bFGF mRNA was highly expressed in the mesometrial decidua at a time when extensive angiogenesis takes place in this tissue. Very little signal was observed in the antimesometrial decidua. To examine the regulation of these growth factors, we used a temperature-sensitive decidual cell line developed by transforming antimesometrial decidual cells with SV-40 tsA 209 mutant virus. These cells express both bFGF and VEGF mRNA. Because progesterone is necessary for decidualization and decidua secretes prolactin (PRL)-related hormones, we examined the role of these hormones on VEGF and bFGF mRNA expressions. Neither progesterone nor PRL had any effect on VEGF mRNA levels. However, bFGF mRNA expression was greatly stimulated by PRL. In conclusion, results of this investigation have revealed that bFGF, but not VEGF, mRNA becomes highly expressed in the mesometrial decidua, where angiogenesis occurs, and where trophoblasts, by invading decidual cells, may promote the release of bFGF. In addition, these results indicate that the locally secreted PRL-like hormone up-regulates the mRNA expression of bFGF.


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