Long-term administration of high-dose methylphenidate-induced cerebellar morphology and function damage in adult rats

Type 1 diabetes mellitus (T1DM) is caused by the autoimmune destruction of pancreatic islet β-cells, which are required for the production of insulin. Islet transplantation has been shown to be an effective treatment option for T1DM; however, the current shortage of human islet donors limits the application of this treatment to patients with brittle T1DM. Xenotransplantation of pig islets is a potential solution to the shortage of human donor islets provided xenograft rejection is prevented. We demonstrated that a short-term administration of a combination of anti-LFA-1 and anti-CD154 monoclonal antibodies (mAbs) was highly effective in preventing rejection of neonatal porcine islet (NPI) xenografts in non-autoimmune-prone B6 mice. However, the efficacy of this therapy in preventing rejection of NPI xenografts in autoimmune-prone nonobese diabetic (NOD) mice is not known. Given that the current application of islet transplantation is for the treatment of T1DM, we set out to determine whether a combination of anti-LFA-1 and anti-CD154 mAbs could promote long-term survival of NPI xenografts in NOD mice. Short-term administration of a combination of anti-LFA-1 and anti-CD154 mAbs, which we found highly effective in preventing rejection of NPI xenografts in B6 mice, failed to promote long-term survival of NPI xenografts in NOD mice. However, addition of anti-CD4 mAb to short-term treatment of a combination of anti-LFA-1 and anti-CD154 mAbs resulted in xenograft function in 9/12 animals and long-term graft (>100 days) survival in 2/12 mice. Immunohistochemical analysis of islet grafts from these mice identified numerous insulin-producing β-cells. Moreover, the anti-porcine antibody as well as autoreactive antibody responses in these mice was reduced similar to those observed in naive nontransplanted mice. These data demonstrate that simultaneous targeting of LFA-1, CD154, and CD4 molecules can be effective in inducing long-term islet xenograft survival and function in autoimmune-prone NOD mice.

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Long-term administration of high-dose deferoxamine 2 days per week in thalassemic patients

European Journal Of Haematology ◽

10.1034/j.1600-0609.2001.00386.x ◽

2001 ◽

Vol 67 (4) ◽

pp. 230-231 ◽

Cited By ~ 5

Author(s):

Isabelle Hagège ◽

Annie Becker ◽

Thierry Kerdaffrec ◽

Alain Kanfer ◽

Robert Girot

Keyword(s):

High Dose ◽

Term Administration

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Growth factors and medium hyperglycemia induce Sox9+ ductal cell differentiation into β cells in mice with reversal of diabetes

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1524200113 ◽

2016 ◽

Vol 113 (3) ◽

pp. 650-655 ◽

Cited By ~ 29

Author(s):

Mingfeng Zhang ◽

Qing Lin ◽

Tong Qi ◽

Tiankun Wang ◽

Ching-Cheng Chen ◽

...

Keyword(s):

Cell Differentiation ◽

Low Dose ◽

Mixed Chimerism ◽

High Dose ◽

Β Cells ◽

Β Cell ◽

Ductal Cells ◽

Ductal Cell ◽

Term Administration

We previously reported that long-term administration of a low dose of gastrin and epidermal growth factor (GE) augments β-cell neogenesis in late-stage diabetic autoimmune mice after eliminating insulitis by induction of mixed chimerism. However, the source of β-cell neogenesis is still unknown. SRY (sex-determining region Y)-box 9+ (Sox9+) ductal cells in the adult pancreas are clonogenic and can give rise to insulin-producing β cells in an in vitro culture. Whether Sox9+ ductal cells in the adult pancreas can give rise to β cells in vivo remains controversial. Here, using lineage-tracing with genetic labeling of Insulin- or Sox9-expressing cells, we show that hyperglycemia (>300 mg/dL) is required for inducing Sox9+ ductal cell differentiation into insulin-producing β cells, and medium hyperglycemia (300–450 mg/dL) in combination with long-term administration of low-dose GE synergistically augments differentiation and is associated with normalization of blood glucose in nonautoimmune diabetic C57BL/6 mice. Short-term administration of high-dose GE cannot augment differentiation, although it can augment preexisting β-cell replication. These results indicate that medium hyperglycemia combined with long-term administration of low-dose GE represents one way to induce Sox9+ ductal cell differentiation into β cells in adult mice.

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Effects of prolactin on the morphology and function of rat Leydig cells: short-term versus long-term administration

Cell and Tissue Research ◽

10.1007/bf00327743 ◽

1990 ◽

Vol 262 (1) ◽

pp. 41-46 ◽

Cited By ~ 2

Author(s):

Giuseppina Mazzocchi ◽

Letizia Cavallini ◽

Aldona Kasprzak ◽

Piera Rebuffat ◽

Gastone G. Nussdorfer

Keyword(s):

Leydig Cells ◽

Short Term ◽

Term Administration ◽

And Function

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Comparison of isoproterenol and dobutamine in the induction of cardiac hypertrophy and fibrosis

Perfusion ◽

10.1177/0267659108100708 ◽

2008 ◽

Vol 23 (4) ◽

pp. 231-235 ◽

Cited By ~ 11

Author(s):

M Anderson ◽

D Moore ◽

DF Larson

Keyword(s):

Cardiac Hypertrophy ◽

Cardiac Function ◽

Cardiac Fibrosis ◽

Detrimental Effect ◽

Chronic Administration ◽

Atrial Size ◽

Term Administration ◽

And Function ◽

Induce Heart Failure

Isoproterenol (Iso) was a clinical therapeutic that is now used as a research means for the induction of cardiac hypertrophy. Currently, dobutamine (Dob) has replaced Iso as the preferred inotropic β-adrenergic agent to wean patients from cardiopulmonary bypass and to sustain adequate cardiac function during the postoperative period. We sought to compare the cardiac structural and functional effects of long-term administration (7days) of Iso with Dob at a dose of 40μg/mouse/day in 12-week-old C57BL/6 female mice. Cardiac function was determined with transthoracic echo cardiography (ECHO) 24 hours after the last dose. Cardiac wet weights increased 33% and 24% in the Iso and Dob groups compared with controls ( p < 0.05). Dob and Iso significantly increased cardiac fibrosis and decreased cardiac function with chronic administration. Administration also resulted in increased left atrial size, suggesting that both Dob and Iso decreased LV compliance, but did not induce heart failure. In conclusion, chronic administration of Dob may have a detrimental effect on cardiac structure and function.

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Treatment of newborn rats with a VEGF receptor inhibitor causes pulmonary hypertension and abnormal lung structure

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00408.2001 ◽

2002 ◽

Vol 283 (3) ◽

pp. L555-L562 ◽

Cited By ~ 254

Author(s):

Timothy D. Le Cras ◽

Neil E. Markham ◽

Rubin M. Tuder ◽

Norbert F. Voelkel ◽

Steven H. Abman

Keyword(s):

Pulmonary Hypertension ◽

Vegf Receptor ◽

Newborn Rats ◽

Long Term Effects ◽

Adult Rats ◽

Rat Pups ◽

Lung Structure ◽

Vegfr Inhibitor ◽

And Function

To determine whether disruption of vascular endothelial growth factor (VEGF)-VEGF receptor (VEGFR) signaling in the newborn has long-term effects on lung structure and function, we injected 1-day-old newborn rat pups with a single dose of Su-5416, a VEGFR inhibitor, or vehicle (controls). Lungs from infant (3-wk-old) and adult (3- to 4-mo-old) rats treated with Su-5416 as newborns showed reductions in arterial density (82 and 31%, respectively) and alveolar counts (45 and 29%) compared with controls. Neonatal treatment with Su-5416 increased right ventricle weight to body wt ratios (4.2-fold and 2.0-fold) and pulmonary arterial wall thickness measurements (2.7-fold and 1.6-fold) in infant and adult rats, respectively, indicating marked pulmonary hypertension. We conclude that treatment of newborn rats with the VEGFR inhibitor Su-5416 impaired pulmonary vascular growth and postnatal alveolarization and caused pulmonary hypertension and that these effects were long term, persisting well into adulthood.

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The Molecular Mechanism of Chronic High-Dose Corticosterone-Induced Aggravation of Cognitive Impairment in APP/PS1 Transgenic Mice

Frontiers in Molecular Neuroscience ◽

10.3389/fnmol.2020.613421 ◽

2021 ◽

Vol 13 ◽

Author(s):

Shen-Qing Zhang ◽

Long-Long Cao ◽

Yun-Yue Liang ◽

Pu Wang

Keyword(s):

Preclinical Model ◽

High Dose ◽

Term Administration ◽

Amyloid Aβ ◽

Β Amyloid ◽

Stimulation Of ◽

Bace 1

Clinical studies have found that some Alzheimer’s disease (AD) patients suffer from Cushing’s syndrome (CS). CS is caused by the long-term release of excess glucocorticoids (GCs) from the adrenal gland, which in turn, impair brain function and induce dementia. Thus, we investigated the mechanism of the effect of corticosterone (CORT) on the development and progression of AD in a preclinical model. Specifically, the plasma CORT levels of 9-month-old APP/PS1 Tg mice were abnormally increased, suggesting an association between GCs and AD. Long-term administration of CORT accelerated cognitive dysfunction by increasing the production and deposition of β-amyloid (Aβ). The mechanism of action of CORT treatment involved stimulation of the expression of BACE-1 and presenilin (PS) 1 in in vitro and in vivo. This observation was confirmed in mice with adrenalectomy (ADX), which had lower levels of GCs. Moreover, the glucocorticoid receptor (GR) mediated the effects of CORT on the stimulation of the expression of BACE-1 and PS1 via the PKA and CREB pathways in neuroblastoma N2a cells. In addition to these mechanisms, CORT can induce a cognitive decline in APP/PS1 Tg mice by inducing apoptosis and decreasing the differentiation of neurons.

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Effect of Short- and Long-Term Administration of Baclofen on Spatial Learning and Memory in Rats

Physiological Research ◽

10.33549/physiolres.933554 ◽

2018 ◽

pp. 133-141 ◽

Cited By ~ 1

Author(s):

M. HOLAJOVA ◽

M. FRANEK

Keyword(s):

Learning And Memory ◽

Spatial Learning ◽

Receptor Agonist ◽

Gabab Receptor ◽

Spatial Learning And Memory ◽

Adult Rats ◽

Treatment Groups ◽

Term Administration ◽

Short And Long Term

Baclofen is the only clinically available metabotropic GABAB receptor agonist. In our experiment, we tested the hypothesis that long-term baclofen administration can impair learning and memory in rats. The experiment consisted of three parts. In the first part of the study the drug was administered simultaneously with the beginning of the behavioral tests. In the second and third part of the experiment baclofen was administered daily for 14 days and for one month before the tests. In each part of the experiment, adult rats were randomly divided into four treatment groups. Three groups were given an injection of baclofen at doses of 1 mg/kg, 5 mg/kg, 10 mg/kg, while the fourth group was injected with saline. The injections were given after each session. Spatial learning and memory were tested using the Morris water maze, involving three types of tests: Acquisition, Probe, and Re-acquisition. This work reveals that baclofen did not affect spatial learning at any of the tested doses and regardless of the length of administration. Memory was observed to be affected, but only at the highest dose of baclofen and only temporarily. This conclusion is in line with previously published clinical cases.

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