1.
Zelleroth, Sofia, 1990-, et al.
(författare)
Structurally different anabolic androgenic steroids reduce neurite outgrowth and neuronal viability in primary rat cortical cell cultures
2021
Ingår i: Journal of Steroid Biochemistry and Molecular Biology. - : Elsevier BV. - 0960-0760 .- 1879-1220. ; 210
Tidskriftsartikel (refereegranskat) abstract
The illicit use of anabolic androgenic steroids (AAS) among adolescents and young adults is a major concern due to the unknown and unpredictable impact of AAS on the developing brain and the consequences of this on mental health, cognitive function and behaviour. The present study aimed to investigate the effects of supra-physiological doses of four structurally different AAS (testosterone, nandrolone, stanozolol and trenbolone) on neurite development and cell viability using an in vitro model of immature primary rat cortical cell cultures. A high-throughput screening image-based approach, measuring the neurite length and number of neurons, was used for the analysis of neurite outgrowth. In addition, cell viability and expression of the Tubb3 gene (encoding the protein beta-III tubulin) were investigated. Testosterone, nandrolone, and trenbolone elicited adverse effects on neurite outgrowth as deduced from an observed reduced neurite length per neuron. Trenbolone was the only AAS that reduced the cell viability as indicated by a decreased number of neurons and declined mitochondrial function. Moreover, trenbolone downregulated the Tubb3 mRNA expression. The adverse impact on neurite development was neither inhibited nor supressed by the selective androgen receptor (AR) antagonist, flutamide, suggesting that the observed effects result from another mechanism or mechanisms of action that are operating apart from AR activation. The results demonstrate a possible AAS-induced detrimental effect on neuronal development and regenerative functions. An impact on these events, that are essential mechanisms for maintaining normal brain function, could possibly contribute to behavioural alterations seen in AAS users.
2.
Ghasemzadeh, Nasim
(författare)
Application of Artificial Gel Antibodies for the Detection and Quantification of Proteins in Biological Fluids
2010
Doktorsavhandling (övrigt vetenskapligt/konstnärligt) abstract
The molecular-imprinting method has previously been used for the synthesis of artificial gel antibodies, highly selective for various proteins. In present study, we have synthesized artificial gel antibodies against haemoglobin, albumin and different forms of growth hormone with the aim to develop a simple and rapid procedure to measure the concentration of these protein biomarkers in samples of clinical interest. A spectrophotometric method was developed to design a standard curve in the form of a straight line, whereby the true absorption (not the recorded “apparent” absorption) was plotted against a known protein concentration. The procedure, applied to quantitative analysis of albumin in human plasma and cerebrospinal fluid (CSF) from patients with ALS, indicated that the concentration of this protein was significantly enhanced in CSF from patients with amyotrophic lateral sclerosis (ALS), compared to control samples. A low level of albumin was observed in plasma from ALS patients compared to controls. Additionally, free zone electrophoresis was employed to detect human growth hormone (GH) activity in hormone preparations purified from human pituitaries. We have successfully synthesized antibodies capable of discriminating between dimeric and monomeric GH in samples of clinical origin. To quantify these proteins a calibration curve has been designed, i.e. a plot of the electrophoretic mobility of the complex GH/gel antibody against the protein concentration in the sample, for instance serum or CSF. This method was also employed for qualitative and quantitative determinations of Somatropin, a non-glycosylated GH and glycosylated-GH in a body liquid. Our results indicate that by this technique one can “fish out” with high accuracy various proteins from both body fluids containing a great number of other proteins. It might well apply also to biomarker proteins for other diseases.
3.
Al Haj, Mahmoud, et al.
(författare)
Effect of Dehydration in the Presence and Absence of the Angiotensin Receptor Blocker Losartan on Blood Constituents in the Camel
2011
Ingår i: Journal of Medical Sciences. - : Hamdan Medical Journal. - 1996-3262 .- 1996-3270. ; 4:2, s. 73-78
Tidskriftsartikel (refereegranskat) abstract
Aim: Dromedary camels are extremely well adapted to periods of water deprivation. The physiological mechanisms underlying this adaptation, however, are imperfectly understood. It is likely that the renin-angiotensin system plays an important role although few studies have addressed this possibility in the camel. Accordingly, the effects of long term dehydration alone and with angiotensin II type 1 receptor blocker, losartan, on whole blood and serum constituents were studied in camels.Methods:Twenty eight male camels 3-4 years old were studied while under shade during summer in the Gulf-region, where the ambient temperature was above 40 degree Celsius. The camels were divided into three groups: a control group(n=6) was allowed free access to feed and water, a dehydration group (n=16) was given food ad-lib during 20days of total water deprivation, and a dehydration plus losartan (losartan) group (n=6) which received losartan 5mg/Kg daily by intravenous injection during 20 days of dehydration. Results: The body weight of the losartan group decreased by nearly 39.1% across dehydration whereas the reduction in body weight for the dehydration group was nearly 34.5% compared to controls. There was a significant increase in the packed cell volume (p<0.05) and leucocytes count (p<0.01) in the losartan group compared to controls. However, the mean corpuscular volume was significantly higher (p<0.05) in the dehydration group compared to controls. We observed major, statistically significant increases in serum urea (p<0.01) and creatinine (p<0.05) levels in the dehydration and losartan groups compared to controls. By the end of the period ofwater restriction, serum levels of gamma glutamyl transferase were significantly (p<0.01) lower in the losartan group compared to controls.Conclusion: The results of our experiment show that dehydration alone or in combination with Angiotensin II receptor blocker has major effects on the biochemical and hematological parameters of the camel blood.
4.
Al Haj, Mahmoud
(författare)
Effects of Dehydration and Blockade of the Renin-Angiotensin System in the One-humped Camel (Camelus dromedarius)
2013
Doktorsavhandling (övrigt vetenskapligt/konstnärligt) abstract
The one-humped or the dromedarian camel is a pseudo-ruminant mammal, well adapted to the hot and dry climates of the desert. Its ability to withstand torrid heat and extreme desiccation is of paramount importance to its survival. The studies presented in this thesis were designed to investigate and document the effect of dehydration in the presence or absence of angiotensin II (Ang II) AT1 receptor blocker (losartan) on blood constituents, electrolytes, hormones, neurotransmitters as well as liver and kidney enzymes in a subset of dehydrated camels and to compare them with hydrated camels. Additionally, we studied the response of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) and revealed for the first time the cardiac storage form of BNP in the camel heart. Dehydration induced significant increments in packed cell volume (PCV), white blood cells (WBC), gamma glutamyl-transferase (GGT), serum sodium, creatinine and urea levels, and a doubling in plasma cortisol and arginine vasopressin (AVP) levels. At the same time dehydration caused significant decrease in body weights, plasma insulin like growth factor-1 (IGF-1) and its binding protein-3 (IGFBP-3), and a 50% decrement in ANP and BNP levels. Moreover, dehydration with and without losartan resulted in significant changes in stress hormones and anti-oxidants in plasma, liver and kidney homogenates. Losartan on one hand enhanced the effect of dehydration resulting in significant increases in sodium, creatinine and urea levels. In addition losartan raised the binding affinity of Ang II AT2 receptors in the small intestine with 8-fold and with 16-fold for liver AT1 receptors, indicating that Ang II AT1 and AT2 receptor binding sites were present in camel's small intestine while only AT1 receptor binding sites were found in the camel liver. One the other hand losartan resulted in significant decrease in body weights impaired the rise in anti-diuretic hormone and reduced aldosterone level. Finally, we showed that the proBNP is the storage form of BNP in the camel heart.
5.
Ali Haj, Mahmoud, et al.
(författare)
Effects of Dehydration and Blockade of Angiotensin II AT1 Receptor on Stress Hormones and Anti-Oxidants in the one-humped camel
2013
Ingår i: BMC Veterinary Research. - : Springer Science and Business Media LLC. - 1746-6148. ; 9, s. 232-
Tidskriftsartikel (refereegranskat) abstract
Our objectives were to document and compare plasma levels of Catecholamines, Cortisol,Glutathione and Malondialdehyde in camels after long term dehydration (20 days) in the presenceor absence of angiotensin II AT1 receptor blocker (Losartan) versus levels in non-dehydratedcamels; and to record the effects on glutathione and malondialdehyde activity in liver and kidneyhomogenate in the one-humped camel. Eighteen male camels were used in this study, sixcontrols, six dehydrated and treated with losartan (5mg/kg daily) and six were dehydrated withouttreatment. Our results revealed significant decrease (P<0.05) in plasma epinephrine level in bothtreated and dehydrated camels; while, Plasma norepinephrine showed significant increase in bothdehydrated groups (P< 0.01). Levels of plasma dopamine were also significantly increased (P<0.01) in both dehydrated groups compared to control camels.Plasma levels of cortisol increased significantly across dehydration with or without losartanadministration (P<0.01) compared with time-matched levels in control camels. Losartan had nosignificant modulating effect on the cortisol response to dehydration.Plasma, liver and kidney homogenates revealed significant increase (P<0.05) in glutathione levelsin both dehydrated groups compared to control.Plasma, liver and kidney homogenates for malondialdehyde levels in both treated and dehydratedcamels also showed significant increase (P<0.05 & P<0.01) compared to controls.In conclusion, our study demonstrates that the effect of dehydration with or without losartaninduced oxidative stress in these camels, leading to significant changes in plasma catecholaminesand cortisol levels, together with significant increments in glutathione and malondialdehydeactivities in plasma, liver and kidney homogenate to counter act the damaging effect of the freeradicals in the dehydrated camels.
6.
Birgner, Carolina, et al.
(författare)
Altered extracellular levels of DOPAC and HVA in the rat nucleus accumbens shell in response to sub-chronic nandrolone administration and a subsequent amphetamine challenge
2007
Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 412:2, s. 168-172
Tidskriftsartikel (refereegranskat) abstract
Associated with acts of violence and polydrug use, abuse of anabolic androgenic steroids (AAS) is an increasing problem in society. The aim of the present study was to elucidate whether sub-chronic treatment with the AAS nandrolone decanoate affects dopamine release and dopamine metabolism in the rat nucleus accumbens shell, before and after an amphetamine challenge. Male Sprague–Dawley rats received daily i.m. injections of nandrolone decanoate (15 mg/kg) or vehicle for 14 days. On day 15, the animals were anaesthetized and a microdialysis probe was implanted into the nucleus accumbens shell. Extracellular fluid was collected 1 h before and 3 h after a single amphetamine injection (5 mg/kg). The samples were then analyzed regarding the content of dopamine, and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), using HPLC with electrochemical detection. Two weeks of nandrolone decanoate administration caused a significant decrease of the basal DOPAC and HVA levels, which remained low during the first hour following the amphetamine challenge. Dopamine levels did not differ significantly between groups, neither after the nandrolone pre-treatment nor the amphetamine challenge. In conclusion, these novel findings indicate that AAS alter the metabolism of dopamine in a brain region involved in the development of drug dependence.
7.
Botros, Milad, et al.
(författare)
Endomorphins interact with the substance P (SP) aminoterminal SP (1-7) binding in the ventral tegmental area of the rat brain
2008
Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 29:10, s. 1820-1824
Tidskriftsartikel (refereegranskat) abstract
We have recently identified a specific binding site for the tachykinin peptide substance P (SP) fragment SP1-7 in the rat spinal cord. This site appeared very specific for SP1-7 as the binding affinity of this compound highly exceeded those of other SP fragments. We also observed that endomorphin-2 (EM-2) exhibited high potency in displacing SP1-7 from this site. In the present work using a [H-3]-labeled derivative of the heptapeptide we have identified and characterized [H-3]-SP1-7 binding in the rat ventral tegmental area (VTA). Similarly to the [H-3]-SP1-7 binding in the spinal cord the affinity of unlabeled SP1-7 to the specific site in VTA was significantly higher than those of other SP fragments. Further, the tachykinin receptor NK-1, NK-2 and NK-3 ligands showed no or negligible binding to the identified site. However, the mu-opioid peptide (MOP) receptor agonists DAMGO, EM-1 and EM-2 did, and significant difference was observed in the binding affinity between the two endomorphins. As recorded from displacement curves the affinity of EM-2 for the SP1-7 site was 4-5 times weaker than that for SP1-7 but about 5 times higher than that of EM-1. The opioid receptor antagonists naloxone and naloxonazine showed weak or negligible binding. it was concluded that the specific site identified for SP1-7 binding in the rat VTA is distinct from the MOP receptor although it exhibits high affinity for EM-2.
8.
Brolin, Erika, et al.
(författare)
Chronic administration of morphine using mini-osmotic pumps affects spatial memory in the male rat
2018
Ingår i: Pharmacology, Biochemistry and Behavior. - : Elsevier BV. - 0091-3057 .- 1873-5177. ; 167, s. 1-8
Tidskriftsartikel (refereegranskat) abstract
The use of opioid analgesics to treat non-cancer pain has increased over the years. Many chronic pain patients suffer from numerous adverse effects, such as reduced quality of life, development of dependence, and cognitive impairments. Cognitive processes are regulated by several systems, one of which involves growth hormone (GH) and its secondary mediator insulin-like growth factor-1 (IGF-1), but also glutamatergic transmission, including receptors such as the N-methyl-D-aspartate (NMDA)-receptor complex. In the laboratory, repeated injections are commonly used to establish animal models of long-term or chronic drug exposure. However, in the present study, we aimed to mimic a more human dose regimen using constant drug delivery provided by mini-osmotic pumps implanted subcutaneously in male Sprague Dawley rats. After developing opioid tolerance the cognitive function of rats was studied. Spatial learning and memory capabilities were evaluated using the rat Morris water maze (MWM). Moreover, gene expression related to the GH/IGF-1-axis and the NMDA-receptor system was analyzed using quantitative PCR (qPCR) and plasma levels of IGF-1 were assessed using the ELISA technique. Our results demonstrate that rats exposed to morphine for 27 days display memory impairments in the MWM probe trial. However, the behavioral effects of chronic morphine treatment were not accompanied by any significant differences in terms of mRNA expression or IGF-1 plasma concentration. The animal model used in this study provides a simple and suitable way to investigate the behavioral and neurochemical effects of chronic opioid treatment similar to the exposure seen in human pain patients.
9.
Brolin, Erika, 1984-
(författare)
Growth hormone in the brain : Focus on cognitive function
2017
Doktorsavhandling (övrigt vetenskapligt/konstnärligt) abstract
Cognitive impairments are an increasing health problem worldwide. In the developed countries, the average life expectancy has dramatically increased over the last decades, and with an elderly population more cases of cognitive impairments appear. Age, genetics, and different medical conditions such as diabetes mellitus, and substance use disorders may all contribute to declined cognitive ability. Physiological functions also decrease with increasing age, as does the activity of the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis. Interestingly, both GH and IGF-1 are recognized for their neuroprotective effects and cognitive enhancement. The overall aim of this thesis was to investigate the impact of the somatotrophic axis (i.e. GH/IGF-1 axis) in rodents with cognitive deficiencies induced by diabetes or long-term drug exposure. For the first time cognitive impairments were characterized in diabetic mice using a spatial learning and memory task called the Barnes maze (BM). In diabetic mice, impaired learning in the BM was associated with decreased expression of the GH receptor (GHR) in the frontal cortex, a region important for e.g. working memory. Treatment with GH reversed certain cognitive impairments seen in diabetic animals. In rats treated with gamma-hydroxybutyrate (GHB), a significant decrease of Igf1 mRNA expression in the frontal cortex was observed. This observation may explain the impaired cognitive function previously seen following GHB administration. Furthermore, rats exposed to chronic morphine delivered in mini-osmotic pumps displayed memory impairments in the Morris water maze (MWM), an effect that seems to be associated with the composition of the N-methyl-d-aspartate (NMDA) receptor complex in the frontal cortex. In conclusion, the result strengthens the evidence for GH being a cognitive enhancer. Moreover, the result within this thesis identifies the frontal cortex as an important brain region, where gene expression related to the somatotrophic system is affected in rodents with cognitive impairments. The thesis especially emphasizes the importance of the local somatotrophic system in the brain with regard to cognitive function.
10.
Brolin, Erika, et al.
(författare)
The mRNA expression of insulin-like growth factor-1 (Igf1) is decreased in the rat frontal cortex following gamma-hydroxybutyrate (GHB) administration
2017
Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 646, s. 15-20
Tidskriftsartikel (refereegranskat) abstract
In recent years, growth hormone (GH), together with its secondary mediators insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-2 (IGF-2), have been highlighted for their beneficial effects in the central nervous system (CNS), in particular as cognitive enhancers. Cognitive processes, such as learning and memory, are known to be impaired in individuals suffering from substance abuse. In the present study, we investigated the effect of gamma-hydroxybuturate (GHB), an illicit drug used for its sedating and euphoric properties, on genes associated with the somatotrophic axis in regions of the brain important for cognitive function. Sprague Dawley rats (n =36) were divided into three groups and administered either saline, GHB 50 mg/kg or GHB 300 mg/kg orally for seven days. The levels of Ghr, Igf1 and Igf2 gene transcripts were analyzed using qPCR in brain regions involved in cognition and dependence. The levels of IGF-1 in blood plasma were also determined using ELISA. The results demonstrated a significant down-regulation of Igf1 mRNA expression in the frontal cortex in high-dose treated rats. Moreover, a significant correlation between Igf1 and Ghr mRNA expression was found in the hippocampus, the frontal cortex, and the caudate putamen, indicating local regulation of the GH/IGF-1 axis. To summarize, the current study concludes that chronic GHB treatment influences gene expression of Ghr and Igf1 in brain regions involved in cognitive function.
