Cerebrospinal Fluid Insulin-like Growth Factor-1 Research Articles

Bergamot essential oil improves CUMS-induced depression-like behaviour in rats by protecting the plasticity of hippocampal neurons.

Bergamot essential oil (BEO) is an extract of the bergamot fruit with significant neuroprotective effect. This study was to investigate the effects and the underlying mechanism of BEO in mitigating depression. GC-MS were used to identify its constituents. Antidepressive properties of BEO were evaluated by sucrose preference test (SPT), force swimming test (FST) and open field test (OFT). Nissl staining was used to determine the number of Nissl bodies in hippocampus (HIPP) of rats. Changes in HIPP dendritic length and dendritic spine density were detected by Golgi-Cox staining. Immunohistochemistry and Western blot were used to detect the postsynaptic density protein-95 (PSD-95) and synaptophysin (SYP) in the HIPP of rats. The enzyme-linked immunosorbent assay was used to determine the 5-hydroxytryptamine (5-HT), insulin-like growth factor 1 (IGF-1) and interleukin-1β (IL-1β) in the HIPP, serum and cerebrospinal fluid (CSF) of rats. Inhaled BEO significantly improved depressive behaviour in chronic unpredictable mild stress (CUMS) rats. BEO increased Nissl bodies, dendritic length and spine density, PSD-95 and SYP protein in the HIPP. Additionally, BEO upregulated serum 5-HT, serum and CSF IGF-1, while downregulating serum IL-1β. Collectively, inhaled BEO mitigates depression by protecting the plasticity of hippocampal neurons, hence, providing novel insights into treatment of depression.

Increased insulin-like growth factor-1 levels in cerebrospinal fluid of advanced subacute sclerosing panencephalitis patients.

Subacute sclerosing panencephalitis (SSPE) is a progressive, lethal disease. Brain histopathology in certain SSPE patients shows, neurofibrillary tangles composed of abnormally phosphorylated, microtubule-associated protein tau (PHF-tau). Because the, phosphorylation of tau is inhibited by insulin and insulin-like growth factor-1 (IGF-1), we investigated cerebrospinal fluid (CSF) insulin and IGF-1 levels in SSPE patients. In this study CSF IGF-1 and insulin levels of 45 SSPE and 25 age-matched control patients were investigated. CSF IGF-1 levels were significantly higher in SSPE patients at stage 4, compared to other stages (p 0.05). CSF insulin and IGF-1 levels were both positively correlated with serum measles IgG. The correlation between CSF insulin and IGF-1 levels and serum measles virus IgG titer may be the result of, insulin activating IGF-1 receptors, and consequently, IGF-1 stimulating, plasma cells and enhancing IgG production. Increased IGF-1 may also, inhibit the phosphorylation of tau. Further studies examining the, correlation between IGF-1, insulin, tau, and PHF-tau levels in the same, patients may clarify any possible pathogenetic relation between these, pathways.

Leptin’s effect on accelerated fracture healing after traumatic brain injury

Objective: To investigate mechanisms behind the faster rehabilitation of limb fractures when associated with traumatic brain injury (TBI).Methods: New Zealand rabbits were divided into TBI group and sham-operation group for four studies as follows: (1) blood and cerebrospinal fluid (CSF) were drawn on days 1, 3, and 7 to demonstrate changes in serum leptin, growth hormone (GH), insulin-like growth factor 1 (IGF-1), and CSF leptin; (2) bone defection was created by drilling in the tibial bone and either leptin or normal saline was injected into rabbit’s cerebellomedullary cistern. X-ray was taken at 1 days, 2 weeks, and 5 weeks and evaluated by criteria to determine rate of bone healing; (3) FITC-labeled rabbit leptin was injected into TBI and sham-operation groups, and frozen sections of rabbit brain were observed to identify differences in central nervous system (CNS) leptin by fluorescence; (4) polymerase chain reaction (PCR) was used to evaluate the expression of leptin production by brain tissue.Results: Serum and CSF leptin, GH, and IGF-1 concentrations were found to be higher in the TBI group than the sham-operation group at days 1, 3, and 7 (P<0·05). CSF leptin of the TBI group was positively correlated with serum leptin on day 1 (P<0·05), and positively correlated with GH and IGF-1 on days 3 and 7 (P<0·05). X-ray criteria demonstrated that leptin administration caused significantly faster healing calluses at 3 and 5 weeks as compared to control animals (P<0·05). FITC-labeled leptin study demonstrated that TBI animals had stronger expression of leptin in the brain than sham-operated animals. However, PCR of brain tissue leptin showed no significant differences between TBI and sham-operated animals in the expression of leptin.Conclusions: Our study suggests that increased CSF leptin, likely from blood–brain barrier breakdown, combined with elevated serum GH and IGF-1 after TBI, leads to accelerated fracture healing.

Expression of Insulin Like Growth Factor in the Cerebrospinal Fluid of Children with Hydrocephalus

Insulin like growth factor-1 (IGF-1) is ubiquitously expressed growth factor that has profound effects on the survival, growth and differentiation of many cell types and tissues, including cells of the central nervous system (CNS). IGF-1 is found in many biological fluids including cerebrospinal fluid (CSF). IGF-1 has broad range neuroprotective effects and is a therapeutic candidate for neurodegenerative diseases. Hydrocephalus is a condition in which there is an abnormal build-up of CSF within the ventricles and/or subarachnoid spaces. Since CSF is in contact with the extracellular space of the brain, biochemical brain modifications could be reflected in the CSF. The aim of this study was to determine the level of CSF IGF-1 level in the children with non-communicating hydrocephalus. A total of 46 samples of CSF from normal and children with hydrocephalic were collected by lumbar puncture performed routinely on the basis of the clinical suspicion of neurological disease. Samples were aged matched between the two groups analyzed. A western blot analysis using anti-IGF-1 antibody as a probe confirmed the presence of IGF-1 in the samples. Quantification of Western blot gels showed that the amount of IGF-1 was increased in the hydrocephalus CSF when compared with normal controls. Using ELISA, it was shown that the concentration of CSF IGF-1 in the hydrocephalus was significantly higher than in controls. The data from this study indicate that IGF-1 is a constant component of human CSF. It is also concluded that high levels of CSF IGF-1 may be partly related to hydrocephalus pathophysiology.

Effects of Fluoxetine Treatment on Striatal Dopamine Transporter Binding and Cerebrospinal Fluid Insulin-Like Growth Factor-1 in Children with Autism

A positive effect of fluoxetine has been shown in some children with autism. The present study was undertaken to correlate striatal dopamine transporter (DAT) binding and cerebrospinal fluid insulin-like growth factor-1 (CSF-IGF-1) with clinical response in autistic children (n=13, age 5-16 years) after a 6-month fluoxetine treatment. Good clinical responders (n=6) had a decrease (p=0.031) in DAT binding as assessed using single-photon emission computed tomography with [123I]-nor-β-CIT, whereas poor responders had a trend to an increase. An increase in CSF-IGF-1 (p=0.003) was detected after the treatment period, but no correlation between the clinical response and CSF-IGF-1 was found. In conclusion, fluoxetine decreases DAT binding indicating alleviation of the hyperdopaminergic state and increases CSF-IGF-1 concentration, which may also have a neuroprotective effect against dopamine-induced neurotoxicity in autistic children.

2FC4.1 Effects of fluoxetine treatment on striatal dopamine transporter binding and cerebrospinal fluid insulin-like growth factor-1 in children with autism

2FC4.1 Effects of fluoxetine treatment on striatal dopamine transporter binding and cerebrospinal fluid insulin-like growth factor-1 in children with autism

Corticotropin-Releasing Factor, Interleukin-6, Brain-Derived Neurotrophic Factor, Insulin-Like Growth Factor-1, and Substance P in the Cerebrospinal Fluid of Civilians With Posttraumatic Stress Disorder Before and After Treatment With Paroxetine

Posttraumatic stress disorder (PTSD) is associated with altered concentrations of stress-related neurohormones, neurotrophins, and neuropeptides in plasma and serum; however, few studies have examined central alterations of these measures in individuals with PTSD. Furthermore, no study to date has evaluated the effects of successful antidepressant treatment on cerebrospinal fluid (CSF) abnormalities in PTSD. Sixteen medication-free outpatients with chronic PTSD (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) due to physical and/or sexual abuse or motor vehicle accidents (mean ± SD age = 36 ± 11.4 years, 12 women) and 11 nontraumatized healthy subjects (mean ± SD age = 35.3 ± 13.1 years, 7 women) underwent a lumbar puncture for collection of CSF. Seven PTSD patients had a repeat lumbar puncture 12 weeks later, after successful treatment of PTSD with paroxetine. CSF was analyzed for corticotropin-releasing factor (CRF), interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and substance P concentrations. The study was conducted between January 2003 and August 2004. Compared to nontraumatized healthy controls, patients with chronic PTSD had similar pretreatment concentrations of CSF CRF, IL-6, BDNF, IGF-1, and substance P. Posttreatment CSF measures did not change significantly in patients whose symptoms remitted with paroxetine. Chronic, moderate PTSD due to civilian trauma, without psychotic symptoms and without significant rates of comorbid depression, alcohol dependence, or substance dependence, is not associated with abnormalities in CSF CRF, IL-6, BDNF, IGF-1, or substance P levels. Despite substantial reduction in PTSD symptoms, antidepressant treatment does not alter normal central concentrations of these neurochemicals, with the possible exception of substance P.

Expression of insulin-like growth factor-1 and insulin-like growth factor binding proteins in the serum and cerebrospinal fluid of patients with Parkinson’s disease

Parkinson’s disease (PD) is characterized by progressive loss of dopaminergic neurons in the substantia nigra. Insulin like growth factor-1 (IGF-1) promotes the survival of dopaminergic neurons and protects them from toxin-induced damage in vitro. IGF-1 is produced by a wide variety of cells and is found in many physiological fluids, including cerebrospinal fluid (CSF). IGFs in physiological fluids are associated with insulin-like growth factor binding proteins (IGFBPs), which bind to them and modulate their bioactivity at the cellular level. Since the CSF is in contact with the extracellular space of the brain, biochemical brain modifications are, to some extent, reflected in the CSF, and peptides and growth factors in the CSF can be used as biomarkers of PD. The aim of this study was to determine the concentrations of IGF-1 and IGFBPs in the serum and CSF of patients with PD. Concentrations were measured in a total of 76 CSF samples from patients with PD ( n = 38) and controls ( n = 38). Serum and CSF IGF-1 and IGFBP concentrations were higher in patients with PD than in controls ( p < 0.001). We conclude that IGF-1 and IGFBPs are always present in human serum and CSF, and may be involved in the pathophysiology of PD.

Insulin like growth factor‐1 and insulin like growth factor binding proteins in the cerebrospinal fluid and serum from patients with Alzheimer's disease

Insulin like growth factor-1 (IGF-1) is ubiquitously expressed growth factor that has profound effects on the growth and differentiation of many cell types and tissues, including cells of the central nervous system (CNS). IGF-1 is produced by a wide variety of cells and is found in many biological fluids including cerebrospinal fluid (CSF). IGF-1 plays important role during CNS development and repair. IGF-1 has broad range neuroprotective effects and is a therapeutic candidate for Huntington's disease (HD). IGF-1 protects striatal neurons from the toxicity of mutated Huntington in vitro and improves neuronal survival in vivo in a phenotypic model of HD. Alzheimer's disease (AD) is an age-dependent dementia characterized by progressive loss of cognitive functions and by characteristic pathological changes in the brain: the formation of aggregates extracellularly by beta-amyloid (AB) peptide and intracellularly by tau proteins. Since cerebrospinal fluid (CSF) is in contact with the extracellular space of the brain, biochemical brain modifications could be reflected in the CSF. IGFs in circulation and other physiological fluids are associated with a group of high-affinity binding proteins insulin like growth factor binding proteins (IGFBPs) that specifically bind and modulate their bioactivity at the cellular level. The aim of this study was to determine the level of CSF and serum IGF-1 and IGFBPs concentrations in the patients with AD. CSF was obtained by lumbar puncture. The presence of IGF-1 and IGFBPs in the CSF and serum samples was confirmed by Western blot using anti-IGF-1 and IGFBPs antibodies. Using enzyme linked immunosorbent assay (ELISA), it was shown that the concentration of CSF and serum IGF-1 and IGFBPs in the patients with AD is higher than in normal control. The data from this study indicate that IGF-1 is a constant component of human CSF. It is also concluded that high levels of CSF IGF-1 may be partly related to AD pathophysiology.

Cerebrospinal fluid insulin-like growth factor-1, insulin growth factor binding protein-2 or nitric oxide are not increased in MS or ALS.

Many studies have shown that nitric oxide (NO) and growth factors including insulin growth factors (IGFs) may be involved in the pathogenesis of multiple sclerosis (MS) and neurodegenerative diseases. Our previous studies suggested a relationship between cerebrospinal fluid (CSF) NO metabolites (nitrates and nitrites, NN(x)) and IGF-1 in patients with progressive encephalopathy, hypsarrhythmia and optic atrophy syndrome. We examined CSF concentrations of NN(x), IGF-1 and IGF binding protein-2 (IGFBP-2) in 25 controls, 14 patients with MS and 14 patients with amyotrophic lateralis sclerosis (ALS). There were no significant differences in CSF levels of NN(x), IGF-1 or IGFBP-2 between the groups. CSF IGFBP-2 concentrations correlated significantly with age in controls, which may reflect age-related changes in the blood-brain barrier function. Upregulation of the production of NO and IGF-1 in the brain or spinal cord does not influence CSF levels of these molecules in MS or ALS.

Insulin-like growth factor-1 and growth hormone (GH) levels in canine cerebrospinal fluid are unaffected by GH or GH secretagogue (MK-0677) administration.

Elevation in circulating GH levels results in a dose-related increase in serum insulin-like growth factor-1 (IGF-1) levels in dogs. However, it is not known whether elevations in systemic IGF-1 and GH levels contribute to the cerebrospinal fluid (CSF) levels of these hormones. Therefore, a study was designed in dogs to determine if elevated circulating GH levels was a result of a GH secretagogue (MK-0677) or if exogenous GH administration resulted in increased IGF-1 and GH levels in the CSF of dogs. A total of 12 normal, young adult male dogs were randomized to three treatment groups (4 dogs/group) based on body weight. There were 4 vehicle control dogs. A group of 4 dogs were dosed orally with MK-0677 (5 mg/kg/day) dissolved in deionized water. A third group of 4 dogs received subcutaneous injections of porcine GH (pGH) at a dose of 0.1 IU/kg/day. From all dogs, blood and CSF samples were collected prior to the initiation of treatment and on days 7 and 15 of treatment. All samples were assayed using a validated radioimmunoassay. Administration of MK-0677 or pGH resulted in a statistically significant (P < or = 0.05) increased body weight gain and increased serum IGF-1 and GH levels. In contrast, administration of MK-0677 resulted in no significant (P > 0.05) increase in CSF IGF-1 or GH levels on days 7 or 15 of the study. The CSF IGF-1 values ranged from 1.2 to 2.0 ng/ml with minimal variation among three separate samples taken during the course of the study from each dog. Similarly, the CSF GH levels were very low (< 0.98 ng/ml to 2.4 ng/ml) in all dogs irrespective of treatment group. This study has demonstrated that there is no correlation between the circulating levels of IGF-1 or GH and the levels of these hormones in the CSF of normal dogs. An approximately 100-fold difference between serum and CSF IGF-1 levels in vehicle control dogs suggest that there is a blood-brain barrier for the circulating IGF-1. Similarly, failure to see an elevation in CSF GH levels despite increases in serum GH levels shows that there is a blood-brain barrier for GH in normal dogs. These results suggest that the likely source of GH and IGF-1 in the CSF of dogs is from the CNS.