Selma Cirrik

Increased Serum Zonulin Levels as an Intestinal Permeability Marker in Autistic Subjects

Objective To evaluate the serum levels of zonulin, which regulates tight junctions between enterocytes and is a physiological modulator controlling intestinal permeability, in patients with autism spectrum disorders (ASDs). Study design Serum zonulin levels were determined in 32 patients with ASD and 33 healthy controls using an enzyme‐linked immunosorbent assay. The severity of ASD symptoms was assessed with the Childhood Autism Rating Scale. Results Serum zonulin levels were significantly higher in the patients with ASD (122.3 ± 98.46 ng/mL) compared with the healthy controls (41.89 ± 45.83 ng/mL). There was a positive correlation between zonulin levels and Childhood Autism Rating Scale score when all subjects were assessed (r = 0.523; P < .001). Conclusions This study suggests that zonulin, which regulates intestinal permeability, plays a role in the development of symptoms of ASD.

Evaluation of serum Neuron-specific enolase, S100B, myelin basic protein and glial fibrilliary acidic protein as brain specific proteins in children with autism spectrum disorder

Brain specific‐proteins are not found in other tissues and measurement non‐invasively in the blood may identify structurally and functionally damaged brain regions and identify the severity and prognosis of neuropsychiatric diseases. For this reason, we aimed to evaluate serum brain‐specific protein values as brain damage markers in children with autism spectrum disorder (ASD).

IGF-1 receptor cleavage in hypertension

Increased protease activity causes receptor dysfunction due to extracellular cleavage of different membrane receptors in hypertension. The vasodilatory effects of insulin-like growth factor-1 (IGF-1) are decreased in hypertension. Therefore, in the present study the association of an enhanced protease activity and IGF-1 receptor cleavage was investigated using the spontaneously hypertensive rats (SHRs) and their normotensive Wistar Kyoto (WKY) controls (n = 4). Matrix metalloproteinase (MMP) activities were determined using gelatin zymography on plasma and different tissue samples. WKY aorta rings were incubated in WKY or SHR plasma with or without MMP inhibitors, and immunohistochemistry was used to quantify the densities of the alpha and beta IGF-1 receptor (IGF-1R) subunits and to determine receptor cleavage. The pAkt and peNOS levels in the aorta were investigated using immunoblotting as a measure of IGF-IR function. Increased MMP-2 and MMP-9 activities were detected in plasma and peripheral tissues of SHRs. IGF-1R beta labeling was similar in both groups without plasma incubation, but the fraction of immunolabeled area for IGF-1R alpha was lower in the endothelial layer of the SHR aorta (p < 0.05). A 24-h incubation of WKY aorta with SHR plasma did not affect the IGF-1R beta labeling density, but reduced the IGF-1R alpha labeling density in the endothelium (p < 0.05). MMP inhibitors prevented this decrease (p < 0.01). Western blot analyses revealed that the pAkt and peNOS levels under IGF-1-stimulated and -unstimulated conditions were lower in SHRs (p < 0.05). A reduced IGF-1 cellular response in the aorta was associated with the decrease in the IGF-1R alpha subunit in the SHR hypertension model. Our results indicate that MMP-dependent receptor cleavage contributed to the reduced IGF-1 response in SHRs.

Increased serum midkine levels in autism spectrum disorder patients

ABSTRACT Background: Midkine (MK) is a heparin binding growth factor and is involved in neurogenesis, neural development and neuroprotection. Additionally, MK may contribute to cancer development and pathogenesis of neurodegenerative disorders and schizophrenia. Considering these effects of MK, this study researched whether MK is involved in autism spectrum disorders (ASD) pathogenesis. Methods: We evaluated serum MK levels of 38 patients with ASD and 32 healthy control group. MK levels were measured with ELISA, while ASD severity was assessed with Childhood Autism Rating Scale. Results: Our data showed that the serum MK concentration in ASD patients (mean ± SD, 11.51 ± 8.53 pg/ml) is significantly higher than healthy controls (mean ± SD, 6.19 ± 3.94 pg/ml) (p = 0.007). Conclusions: According to these results, MK may play a role in ASD pathogenesis.

Endoplasmic reticulum stress in the livers of BDNF heterozygous knockout mice

Abstract Context: Involvement of endoplasmic reticulum (ER) stress and brain-derived neurotrophic factor (BDNF) in hepatic lipid metabolism has been reported previously. Objective: The effects of chronic BDNF deficiency on ER stress response in the livers were examined in this study. Methods: BDNF(+/−) mice, characterised by BDNF deficiency, and their wild-type (WT) littermates were used. The ER stress was induced by tunicamycin (Tm) (0.5 mg/kg, intraperitoneal). Animals were divided into four groups; WT, WT + Tm, BDNF(+/−), and BDNF(+/−)+Tm. Results: At the basal conditions, BDNF deficiency did not affect hepatic cell death or lipid accumulation. However, during ER stress, BDNF(+/−)+Tm group showed increased apoptosis, GADD153 immunostaining, sterol regulatory element-binding protein-1c (SREBP-1c) level, and steatosis compared to the WT + Tm group. Conclusion: Endogenous BDNF might be protective against apoptosis through GADD153 suppression and steatosis via SREBP-1c suppression during ER stress. This effect of BDNF might be clinically important for type 2 diabetes and obesity, which are related with both ER stress and BDNF deficiency.

The Effect of Tadalafil on Renal Fibrosis Induced by Ureteral Obstruction

Objective: It has been reported that phosphodiesterase-5 (PDE-5) inhibitors improve kidney function during acute and chronic renal failure. This study aimed to determine the possible therapeutic effects of tadalafil, a specific PDE-5 inhibitor, on renal fibrosis induced by unilateral ureteral obstruction (UUO). Methods: Male Sprague-Dawley rats were used and randomly divided into three groups (n = 6) as sham-operated, UUO and tadalafil-treated (10 mg/72 hours, ig) UUO (UUO+T) groups. Unilateral ureteral obstruction was induced by complete ligation of the left ureter and 14 days after surgery creatinine clearance, urinary cyclic guanosine monophosphate (cGMP), renal alpha-smooth muscle actin (α-sma) and transforming growth factor βeta (TGF-β) levels, as well as histologic changes, were observed in all the animals. Results: Unilateral ureteral obstruction-induced renal fibrosis was confirmed by increased α-sma level, collagen deposition, tubular dilation, inflammatory cell infiltration and necrosis. An increased renal TGF-β level and decreased urinary cGMP level was also observed in obstructed animals in addition to reduced creatinine clearance. Tadalafil treatment, which restored the animals’ urinary cGMP level, significantly attenuated the fibrotic changes and TGF-β increase in their kidneys. Conclusion: This study suggests that tadalafil treatment ameliorates renal fibrosis by reducing TGF-β expression and may have important clinical relevance since tadalafil is currently used clinically to treat erectile dysfunction and pulmonary hypertension.

The effect of trimetazidine on renal oxidative stress in partialand complete ureteral obstructions in a rat model

BACKGROUND/AIM Renal oxidative stress occurs in ureteral obstructions. The purpose of this study was to investigate the effect of the antioxidant and antiischemic agent trimetazidine (TMZ) on oxidative stress following ureteral obstruction. MATERIALS AND METHODS Ten groups were established. Sham groups were checked as controls after 1 and 3 weeks. The other 8 groups had partial or complete ureteral obstruction while receiving or not receiving trimetazidine (TMZ) at 5 mg/kg daily and were evaluated after either 1 week or 3 weeks. Creatinine and cystatin C measurements were performed in the serum. Malondialdehyde, myeloperoxidase, catalase, and glutathione peroxidase activity were measured in renal tissue and serum. RESULTS In the 1-week groups, tissue malondialdehyde, serum myeloperoxidase, and glutathione peroxidase activity increased significantly with obstruction and TMZ use compared to the control group (P < 0.005). In the 3-week TMZ group, cystatin C, tissue malondialdehyde, serum and tissue myeloperoxidase, and tissue glutathione peroxidase differed significantly (P < 0.05). There was no significant difference in all parameters after 3 weeks of partial obstruction (P > 0.05), with only serum malondialdehyde being significantly elevated (P < 0.05). CONCLUSION TMZ did not exhibit a renal oxidative stress-lowering effect in obstruction. It causes mild impairment of renal functions in obstruction. Patients using TMZ must be closely monitored in terms of kidney function in the event of any ureteral obstruction.

Neurophysiological Effects of Exercise

Convincing findings from animal and clinical studies have shown that exercise improves mood and cognition in addition to cardiovascular and metabolic benefits. Exercise, with the greatest effects on the hippocampus, which has a central role in learning and memory, increases neurogenesis and synaptic plasticity. Although the exact molecular mechanisms responsible for the exercise-induced neuroplasticity need to be clarified, some neurotrophic and angiogenic factors (e.g. BDNF, IGF-1, bFGF2 and VEGF) and different neurotransmitter systems (glutamate, GABA, endocannabinoids and monoamines) may have critical contributions in these processes. Exercise-induced changes in the brain morphology, chemistry and functions seem to be responsible for the beneficial effects of exercise, like improved learning and memory, anti-depressant-like and anxiolytic effects, reduced cognitive decline related to ageing and improvements in symptoms of neurodegenerative diseases. In this chapter, after discussing basic neurophysiological information regarding the brain, cognition, neurotransmitter systems, neural plasticity, learning, memory and behaviour tasks, the focus is on the exercise-induced changes in neuroplasticity, cognitive functions and mood and the factors mediating the effects of exercise, and finally, the effect of exercise on ageing and neurodegenerative diseases is discussed.