tissue levels
Recently Published Documents


TOTAL DOCUMENTS

919
(FIVE YEARS 62)

H-INDEX

59
(FIVE YEARS 2)

Author(s):  
Olivier Le Bacquer ◽  
Jérôme Salles ◽  
Fabiana Piscitelli ◽  
Phelipe Sanchez ◽  
Vincent Martin ◽  
...  

2021 ◽  
Vol 12 (4) ◽  
pp. 045008
Author(s):  
Fatemeh Saadatpour ◽  
Fatemeh Mohammadipanah ◽  
Nazanin Zohourian ◽  
Mahshid Hodjat

Abstract Aging is an inevitable process caused by the accumulation of degenerative destructions, which ultimately leads to organism death. As the aging process occurs at the molecular, cellular, and tissue levels, understanding the whole details of age-related disorders is the prerequisite for the development of anti-aging therapy. More than 300 compounds of different sources have been reported with an anti-aging activity that controls age-related diseases through regulating single or multiple signalling pathways. Recent innovations in nanotechniques could lead to the development of nanomaterials having effects on age-associated malfunctions or acting as nanocarrier systems and distributers of anti-aging drugs. In this review, we summarised the molecular mechanisms of longevity and the prospect of developing anti-aging nanomaterials targeting aging pathways.


2021 ◽  
Author(s):  
◽  
Jennifer Do

<p>Rationale: Over the past few decades, MDMA has been shown to produce persistent detrimental effects. Animal models have been developed to investigate the effects of self-administered drugs on brain and behaviour, but only a limited number of studies have investigated effects of MDMA. Objectives: The present thesis sought to determine the effects of MDMA self-administration on working memory and tissue levels of 5HT in rats. The role of the 5HT₁ₐ autoreceptor in MDMA-produced deficits in tissue levels of 5HT was also evaluated using neurochemical and behavioural assays. Methods: Rats self-administered a total of 165mg/kg MDMA, and were then tested in the Novel Object Recognition (NOR) task 1 week or 9 weeks following the last session of MDMA self-administration. Tissue levels of 5HT were measured in separate groups of rats, following self-administration of a total dose of 165mg/kg or 315mg/kg. 8-OH-DPAT-induced lower lip retraction (LLR) was measured in rats 2 weeks following either self-administered (315mg/kg) or experimenter-administered (40mg/kg) MDMA. In subsequent studies, chronic 8-OH-DPAT (daily injections over 7 days; 1.0mg/kg/day), chronic trazodone (continuous infusion over 14 days via osmotic minipump; 10mg/kg/day) and tryptophan loading (oral administration over 7 days; 125mg/day via gavaging needle) were administered after MDMA treatment (either self-administered; 315mg/kg or experimenter-administered; 40mg/kg) and tissue levels of 5HT were measured. Results: Self-administered MDMA produced deficits in NOR that recovered 10 weeks following self-administration. There was a small decrease in tissue levels of 5HT at both 2 weeks and 10 weeks following the low dose of self-administered MDMA. Two weeks following the high dose, tissue levels of 5HT were decreased by about 30% in all brain regions examined, and there was recovery 10 weeks following exposure. 8-OH-DPAT-induced LLR was unchanged in MDMA-treated rats. Furthermore, none of the treatments restored tissue levels of 5HT following MDMA exposure, even though the treatment (chronic 8-OH-DPAT) shifted the basal 8-OH-DPAT-induced LLR curve to the right, suggesting autoreceptor desensitisation. Conclusions: Self-administered MDMA produced deficits in NOR, which may reflect impaired attention, encoding, novelty seeking or other cognitive processes. Dose- and time-dependent deficits in tissue levels of 5HT were modest compared to those produced by experimenter-administered MDMA. Therefore, MDMA self-administration may be important for pre-clinical investigation of long-term consequences of MDMA. The findings are not consistent with the idea that the 5HT₁ₐ autoreceptor became supersensitive as a result of MDMA exposure, and it is therefore not a viable pharmacological target for restoring tissue levels of 5HT.</p>


2021 ◽  
Author(s):  
◽  
Jennifer Do

<p>Rationale: Over the past few decades, MDMA has been shown to produce persistent detrimental effects. Animal models have been developed to investigate the effects of self-administered drugs on brain and behaviour, but only a limited number of studies have investigated effects of MDMA. Objectives: The present thesis sought to determine the effects of MDMA self-administration on working memory and tissue levels of 5HT in rats. The role of the 5HT₁ₐ autoreceptor in MDMA-produced deficits in tissue levels of 5HT was also evaluated using neurochemical and behavioural assays. Methods: Rats self-administered a total of 165mg/kg MDMA, and were then tested in the Novel Object Recognition (NOR) task 1 week or 9 weeks following the last session of MDMA self-administration. Tissue levels of 5HT were measured in separate groups of rats, following self-administration of a total dose of 165mg/kg or 315mg/kg. 8-OH-DPAT-induced lower lip retraction (LLR) was measured in rats 2 weeks following either self-administered (315mg/kg) or experimenter-administered (40mg/kg) MDMA. In subsequent studies, chronic 8-OH-DPAT (daily injections over 7 days; 1.0mg/kg/day), chronic trazodone (continuous infusion over 14 days via osmotic minipump; 10mg/kg/day) and tryptophan loading (oral administration over 7 days; 125mg/day via gavaging needle) were administered after MDMA treatment (either self-administered; 315mg/kg or experimenter-administered; 40mg/kg) and tissue levels of 5HT were measured. Results: Self-administered MDMA produced deficits in NOR that recovered 10 weeks following self-administration. There was a small decrease in tissue levels of 5HT at both 2 weeks and 10 weeks following the low dose of self-administered MDMA. Two weeks following the high dose, tissue levels of 5HT were decreased by about 30% in all brain regions examined, and there was recovery 10 weeks following exposure. 8-OH-DPAT-induced LLR was unchanged in MDMA-treated rats. Furthermore, none of the treatments restored tissue levels of 5HT following MDMA exposure, even though the treatment (chronic 8-OH-DPAT) shifted the basal 8-OH-DPAT-induced LLR curve to the right, suggesting autoreceptor desensitisation. Conclusions: Self-administered MDMA produced deficits in NOR, which may reflect impaired attention, encoding, novelty seeking or other cognitive processes. Dose- and time-dependent deficits in tissue levels of 5HT were modest compared to those produced by experimenter-administered MDMA. Therefore, MDMA self-administration may be important for pre-clinical investigation of long-term consequences of MDMA. The findings are not consistent with the idea that the 5HT₁ₐ autoreceptor became supersensitive as a result of MDMA exposure, and it is therefore not a viable pharmacological target for restoring tissue levels of 5HT.</p>


2021 ◽  
Author(s):  
◽  
Karen Jones

<p>Rationale: Following repeated +/-3,4- methylenedioxymethamphetamine (MDMA) administration there is tolerance to many behavioural effects and deficits in serotonergic neurotransmission. Objectives: The present studies had three main objectives. 1. To develop a behavioural assay to examine the effects of acute and repeated MDMA exposure. 2. To use this behavioural assay to determine whether functional changes in serotonin (5-HT)2a or 5-HT2c receptors accompany tolerance to the effects of MDMA. 3. To attempt to reverse behavioural tolerance and 5-HT deficits by administering a treatment that has been shown to desensitise the 5-HT1a autoreceptor. Methods: In separate groups of rats the dose effect curves for MDMAproduced hyperactivity were determined (0.0, 1.0, 3.3, 10.0 mg/kg). In additional groups the effect of MDMA pretreatment (4 X 10mg/kg MDMA injections at 2 hour intervals) or saline vehicle on MDMA-produced hyperactivity was assessed. To determine the experimental parameters for MDMA effects in the Emergence Test (ET) separate groups of rats received MDMA (0.0, 3.3 mg/kg) and were either habituated to a hide box for various periods (15, 30, 45mins) or exposed to the test arena 3 times over a period of days (day 1, 5, 9) or injected daily in the home cage with MDMA (0.0, 3.3mg/kg) for 3 days. Emergence latency following injections of MDMA (0.0, 3.3mg/kg), the 5-HT2a /c agonistm-CPP (0.0, 0.3, 0.6 or 1.25 m/kg), the 5-HT releasing stimulant, fenfluramine (0.0, 1.0, 2.0 mg/kg), and the 5-HT2a agonist DOI (0.0, 1.0, 2.0 mg/kg) was measured. The role of 5-HT2c receptors was assessed by determining the effect of the 5-HT2c antagonist, RS102221 (0.0, 0.25, 0.5, 1.0 mg/kg). The effect of MDMA pretreatment on MDMA (0.0, 3.3 mg/kg), m-CPP (1.25 mg/kg), or fenfluramine (2.0mg/kg) induced increases in emergence latency was also assessed. The functional status of the 5-HT1a autoreceptor following MDMA pretreatment was determined by measuring the effect of the 5-HT1a agonist, 8- OHDPAT (0.0, 0.315, 0.0625, 0.125, 0.25, 0.5 mg/kg, SC), on body temperature. The ability of the 5-HT1a antagonist, WAY100635 (0.0, 0.01, 0.1, 1.0mg/kg, SC, 1 X daily for 7 days or by local injection of 0.0 or 500 ng into the dorsal raphe) to reverse the attenuation of MDMA-induced hyperactivity following MDMA pretreatment was examined. Effects of various treatments on tissue levels of 5-HT and 5-HIAA were also measured using HPLC with EC. Results: MDMA produced dose-dependent hyperactivity and tolerance was produced by MDMA pretreatment. MDMA (3.3mg/kg) increased emergence latency following a 30 minute habituation period and this effect was reduced in MDMA-pretreated rats. Fenfluramine and m-CPP but not DOI also increased emergence latency in a dose-dependent manner. RS102221 dose dependently blocked the acute effects of MDMA and m-CPP. Two weeks following MDMA pretreatment rats were tolerant to the effects of MDMA and fenfluramine, but not m-CPP. MDMA pretreatment also produced significant reductions in tissue levels of 5-HT and 5-HIAA. Subcutaneous WAY100635 administration failed to reverse the behavioural and neurochemical deficits produced by MDMA pretreatment but local administration increased MDMA-produced hyperactivity in saline and MDMA pretreated rats and reversed MDMA-produced 5-HT tissue depletions. Conclusion: The Emergence Test is a behavioural assay sensitive to the effects of acute and repeated MDMA exposure. Following MDMA pretreatment behavioural tolerance as measured by the ET is likely to be due to impaired 5-HT release rather than changes in 5-HT2a or 5-HT2c receptor responses. Because partial reversal of tolerance and 5-HT deficits following repeated MDMA administration was achieved through local DRN 5-HT1a antagonist administration the 5-HT1a autoreceptor may prove to be a clinical target for the reversal of MDMA produced deficits.</p>


2021 ◽  
Author(s):  
◽  
Karen Jones

<p>Rationale: Following repeated +/-3,4- methylenedioxymethamphetamine (MDMA) administration there is tolerance to many behavioural effects and deficits in serotonergic neurotransmission. Objectives: The present studies had three main objectives. 1. To develop a behavioural assay to examine the effects of acute and repeated MDMA exposure. 2. To use this behavioural assay to determine whether functional changes in serotonin (5-HT)2a or 5-HT2c receptors accompany tolerance to the effects of MDMA. 3. To attempt to reverse behavioural tolerance and 5-HT deficits by administering a treatment that has been shown to desensitise the 5-HT1a autoreceptor. Methods: In separate groups of rats the dose effect curves for MDMAproduced hyperactivity were determined (0.0, 1.0, 3.3, 10.0 mg/kg). In additional groups the effect of MDMA pretreatment (4 X 10mg/kg MDMA injections at 2 hour intervals) or saline vehicle on MDMA-produced hyperactivity was assessed. To determine the experimental parameters for MDMA effects in the Emergence Test (ET) separate groups of rats received MDMA (0.0, 3.3 mg/kg) and were either habituated to a hide box for various periods (15, 30, 45mins) or exposed to the test arena 3 times over a period of days (day 1, 5, 9) or injected daily in the home cage with MDMA (0.0, 3.3mg/kg) for 3 days. Emergence latency following injections of MDMA (0.0, 3.3mg/kg), the 5-HT2a /c agonistm-CPP (0.0, 0.3, 0.6 or 1.25 m/kg), the 5-HT releasing stimulant, fenfluramine (0.0, 1.0, 2.0 mg/kg), and the 5-HT2a agonist DOI (0.0, 1.0, 2.0 mg/kg) was measured. The role of 5-HT2c receptors was assessed by determining the effect of the 5-HT2c antagonist, RS102221 (0.0, 0.25, 0.5, 1.0 mg/kg). The effect of MDMA pretreatment on MDMA (0.0, 3.3 mg/kg), m-CPP (1.25 mg/kg), or fenfluramine (2.0mg/kg) induced increases in emergence latency was also assessed. The functional status of the 5-HT1a autoreceptor following MDMA pretreatment was determined by measuring the effect of the 5-HT1a agonist, 8- OHDPAT (0.0, 0.315, 0.0625, 0.125, 0.25, 0.5 mg/kg, SC), on body temperature. The ability of the 5-HT1a antagonist, WAY100635 (0.0, 0.01, 0.1, 1.0mg/kg, SC, 1 X daily for 7 days or by local injection of 0.0 or 500 ng into the dorsal raphe) to reverse the attenuation of MDMA-induced hyperactivity following MDMA pretreatment was examined. Effects of various treatments on tissue levels of 5-HT and 5-HIAA were also measured using HPLC with EC. Results: MDMA produced dose-dependent hyperactivity and tolerance was produced by MDMA pretreatment. MDMA (3.3mg/kg) increased emergence latency following a 30 minute habituation period and this effect was reduced in MDMA-pretreated rats. Fenfluramine and m-CPP but not DOI also increased emergence latency in a dose-dependent manner. RS102221 dose dependently blocked the acute effects of MDMA and m-CPP. Two weeks following MDMA pretreatment rats were tolerant to the effects of MDMA and fenfluramine, but not m-CPP. MDMA pretreatment also produced significant reductions in tissue levels of 5-HT and 5-HIAA. Subcutaneous WAY100635 administration failed to reverse the behavioural and neurochemical deficits produced by MDMA pretreatment but local administration increased MDMA-produced hyperactivity in saline and MDMA pretreated rats and reversed MDMA-produced 5-HT tissue depletions. Conclusion: The Emergence Test is a behavioural assay sensitive to the effects of acute and repeated MDMA exposure. Following MDMA pretreatment behavioural tolerance as measured by the ET is likely to be due to impaired 5-HT release rather than changes in 5-HT2a or 5-HT2c receptor responses. Because partial reversal of tolerance and 5-HT deficits following repeated MDMA administration was achieved through local DRN 5-HT1a antagonist administration the 5-HT1a autoreceptor may prove to be a clinical target for the reversal of MDMA produced deficits.</p>


2021 ◽  
Vol 22 (21) ◽  
pp. 11973
Author(s):  
Yuriy L. Orlov ◽  
Tatiana V. Tatarinova ◽  
Anastasia A. Anashkina

Gene expression regulation at the transcriptome, genome, cell, and tissue levels is a complex phenomenon demanding the development of bioinformatics tools [...]


Author(s):  
Heba Ahmed Abdelkader ◽  
Laila Ahmed Rashed ◽  
Eman Assaad ◽  
Marwah Adly Saleh

Sign in / Sign up

Export Citation Format

Share Document