The Expression of Neurodegeneration-Related Genes in the Hippocampus of Hypothyroid Rats Following Long-Term Potentiation.

BACKGROUND:  In our research, we examined how the induction of long-term potentiation (LTP) in the hippocampus of hypothyroid rats afects the mRNA levels of several proteins involved with neurodegeneration, including Gsk3, Cdk5, Akt1, Mapt, P35 (Anxa), Capn1, Bace1, and Psen2. METHODS:  Wistar-albino rats, consisting of 12 males, were used in the research, and they were separated into 2 groups: control (n=6) and hypothyroidism (n=6). To induce hypothyroidism, propylthiouracil was added to drinking water at a dosage of 20 mg/kg/day. The test stimulus intensity was calculated, basal recordings were acquired, and LTP was induced by administering 100 Hz high-frequency stimulation (HFS) for 1 second with a 5-minute delay when the rats were aged 60 days. The population spike (PS) amplitude and excitatory postsynaptic potential (EPSP) slope were measured in the granule cell layer of the dentate gyrus. Using reverse transcription polymerase chain reaction, the mRNA levels of neurodegenerative genes were assessed in induced hippocampal tissues after the LTP protocol. The free T4 levels in plasma were measured using a plate reader with the commercial ELISA kit. RESULTS:  Following HFS, LTP was solely induced in the EPSP slope and PS amplitude in the control group. The impaired LTP response of the hypothyroidism group was accompanied by an increase in Akt1-mRNA expression and a decrease in Gsk3ß expression, whereas the value genes' mRNA expression levels did not difer significantly from those of the control group. CONCLUSION:  The hypothyroidism-related LTP impairment could be caused by a reduction in PI3K/AKT signaling. Further investigation of this path is required to elucidate the pathophysiology of impaired synaptic plasticity in hypothyroidism.

Phosphorylation of tau protein based on the activity of kinases and phosphatases in various forms of synaptic plasticity.

The aim of this study is to show the relationship between the change in the strengthening of synaptic plasticity and tau phosphorylation and tau-kinases and phosphatase. The averages of the field excitatory-postsynaptic potential (fEPSP) and population spike (PS) in the last 5 min were used as a measure of LTP, LTD and MP. Total and phosphorylated levels of tau, kinases and phosphatases were evaluated by western blot and mRNA levels were evaluated by RT-qPCR. The stimulation of synapses by HFS and LFS+HFS increased the phosphorylation of total-tau and phospho-tau at the Thr181, Ser202/Thr205, Ser396 and Ser416 residues, and these were accompanied by increased enzymatic activity of Akt, ERK1/2. The increased phosphorylation of tau may mediate maintenance of LTP. If the increase in phosphorylation of tau cannot be prevented, together with inhibition of the subsequent LTP, this may indicate that the physiological role of hyperphosphorylated tau in synaptic plasticity may extend to pathological processes.

Insulin-induced long-term potentiation in the dentate gyrus of hippocampal formation.

The discovery that brain areas involving in learning and memory express receptors for insulin hormone, led to the idea that insulin signaling may have a role in regulating cognitive function. Although previous studies have shown a role for insulin in regulation of the threshold of plasticity induction, no study has addressed whether insulin can induce a chemical plasticity per se. Young-adult male rats that are fed with standard diets with or without carbohydrate syrup (sucrose or high-fructose corn syrups) were enrolled in this study. Extracellular field potentials were recorded from the dentate gyrus in response to perforant pathway stimulation at 0.033 Hz in anesthetized rats. The slope of field excitatory postsynaptic potentials (fEPSPs) and the amplitude of population spike (PS) were measured 15 min after a 60-min infusion of insulin (500 nM), NT157 (an IRS inhibitor, 6 µM), alone or together, or physiological saline. mRNA expressions of insulin signaling proteins were measured by rt-PCR in the whole hippocampus. We did not observe any appreciable change in the fEPSP slope and the PS amplitude before and after saline infusion. However, intra-hippocampal insulin application results in the induction of LTP of fEPSP and of PS in the dentate gyrus. Insulin infusion together with NT157 inhibited fEPSP-LTP, but not PS-LTP, and rats that are fed with carbohydrate syrup did not express synaptic LTP. In rats that additional carbohydrate syrup is not given, insulin-induced LTP was accompanied with an increase in PI3K-mRNA, AKT-mRNA, and GSK-3ß-mRNA which was not observed when co-administered with NT157. The GSK-3ß-mRNA and IRS1-mRNA levels were found to be lower in rats that received supplemental carbohydrate and that not express insulin-induced synaptic LTP, compared to the rats expressing synaptic LTP and fed by standard diet. The results obtained provide a mechanistic link between insulin and synaptic plasticity. We concluded that insulin not only functions as a modulator of synaptic plasticity but also acts as a chemical inducer of LTP.

Neurodegeneration-related genes are differentially expressed in middle-aged rats compared to young-adult rats having equal performance on long-term memory and synaptic plasticity.

The present study is concerned with assessing differences in plasticity-induced neurodegeneration-related gene expressions and tau phosphorylation between young-aged and middle-aged rats. The experiments were carried out in vivo under urethane anesthesia on adult male Wistar rats between the ages of 2-3 months and 11-12 months. Field potentials, composed of a field of excitatory-postsynaptic potential (fEPSP) and a population-spike (PS), were recorded from granule cells of the dentate gyrus. Plasticity was induced by high-frequency (HFS) or low frequency stimulation (LFS). mRNA of neurodegeneration-related genes and total-and phosphorylated-tau were measured in HFS-and LFS-induced hippocampus by using quantitative rt-PCR and Western blotting. In addition, naive rats (unstimulated) were tested for spatial learning and memory with a 5-day Morris water maze (MWM). HFS-induced LTP of PS had attenuated in middle-aged rats, but there were no gross differences in baseline synaptic function, HFS-induced fEPSP and LFS-induced fEPSP, and PS plasticity between young-aged and middle-aged rats. Relative to young-aged rats, in middle-aged rats, HFS-induced MAPT, CDK5, and AKT1 genes were more up regulated, while LFS-induced Bace1, PSEN2, CAPN1, ANXA, CDK5, and GSK-3ß genes were more down-regulated. Tau and p-tauThr231 were increased by HFS/LFS in the hippocampus of middle-aged rats compared to those of young-aged rats. In MWM, despite the difference in searching strategy of both age groups of rats, memory was not affected by age. Impaired long-term potentiation (LTP) and accompanying changes in intracellular biological markers may underlie in neurodegenerative disease characterized by dementia that occurs gradually later ages. However, these changes were not reflected in behavioral spatial memory.

Subtracted Adulthood Mass Index - a new index to predict NAFLD risk in non-obese individuals.

Background and Aim: Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease. The aims of the current study are to determine the relationship between NAFLD in non-obese individuals and weight gain during adulthood and develop a new index for the identification of NAFLD risk. Materials and Methods: For this cross-sectional study, 362 patients who underwent abdominal ultrasonography (USG) in our clinic were included. Seventy-eight individuals were obese (>30 kg/m2). A history of weight gain during adulthood and systemic metabolic diseases was collected at the time of the study. A new index termed "Subtracted Adulthood Mass Index" (SAMI) was created to estimate the risk of NAFLD development for non-obese people. SAMI is the ratio of the difference between the individual's current weight and his/her weight at 20 years old to his/her height squared (kg/m2). Results: When the SAMI cut-off was set at 3 kg/m2, the sensitivity for predicting NAFLD risk was 85.2%, the specificity was 66.9%, the PPV was 79.1%, and the NPV was 75.4%. Conclusion: In this innovational study, a new index named SAMI was developed to identify non-obese people who are at risk of developing NAFLD. The SAMI is easy to calculate and appropriate for clinical use.

Long-term depression-related tau phosphorylation is enhanced by methylene blue in healthy rat hippocampus.

BACKGROUND: The present study examined whether inhibition of guanylate cyclase (GC) is associated with the plasticity-related microtubule-stabilizing protein tau phosphorylation in the dentate gyrus (DG) of hippocampal formation. METHODS: To address this issue, methylene blue (MB 50 µM) or saline was infused into the DG starting from the induction of long-term potentiation (LTP) or depression (LTD) for 1 h. Then, protein phosphatase 1 alpha (PP1α), glycogen synthase kinase 3 beta (GSK3ß), and tau total and phosphorylated protein levels were measured in these hippocampi using western blotting. LTP and LTD were induced by application of high- and low-frequency stimulation protocols (HFS and LFS), respectively. 5-min averages of the excitatory postsynaptic potential (EPSP) slopes and population spike amplitudes at the end of recording were averaged to measure the magnitude of LTP or LTD. RESULTS: Low-frequency stimulation protocols was unable to phosphorylate thr181 and thr231epitopes of tau, but possessed kinase activity similar to the HFS in phosphorylation of ser396 and ser416 epitopes. MB infusion during LTD induction attenuated LTD, prevented EPSP/spike dissociation and increased tau phosphorylation at ser396 and ser416 epitopes, without changing tau phosphorylation at thr181 and thr231 epitopes. Neither LTP nor LTP-related tau phosphorylation state was changed by MB infusion. CONCLUSION: Although MB can benefit to stabilize the balance between LTP and LTD, and to fix the increased spike wave discharges, it might trigger deregulation of tau phosphorylation, leading to the development of Alzheimer's disease by a mechanism that goes awry during induction of LTD. Thereby detailed studies to reveal more precise evidence for the use of MB in this disease are needed.

MRI evaluation of cranial bone marrow signal intensity and thickness in chronic anemia.

BACKGROUND AND PURPOSE: The aim is to assess the magnetic resonance imaging (MRI) findings for cranial bone marrow (CBM) signal intensity and thickness in patients with chronic anemia and compared these with findings in healthy subjects. We also investigated the relationships between CBM changes and age, type of anemia (hemolytic versus non-hemolytic), and severity of anemia. METHODS: We quantitatively evaluated CBM signal intensity and thickness on images from 40 patients with chronic anemia (20 with congenital hemolytic anemia (HA) and 20 with acquired anemia) and compared these to findings in 28 healthy subjects. The intensity of CBM relative to scalp, white matter (WM), gray matter (GM), and muscle intensity was also investigated in patients and subjects in the control group. The sensitivity and specificity of CBM hypointense to GM and CBM hypointense to WM as markers of anemia were evaluated. Relationships between age and CBM thickness/intensity, and between anemia severity (hemoglobin (Hb) level) and CBM thickness/intensity were evaluated. RESULTS: Cranial bone marrow signal intensity was lower in the chronic anemia patients than in the controls (P<0.001). In the control group, CBM intensity was higher than GM intensity, whereas the opposite was true in the patient group. The finding of CBM hypointense to GM was 85% sensitive and 67% specific as a marker of anemia. The corresponding statistics for CBM hypointense to WM were 90 and 46%. The patients had thicker CBM than the controls (temporal, P<0.05; parietal, P<0.005). The subgroup with hemolytic anemia had thicker parietal CBM than the subgroup with non-hemolytic anemia (NHA) (P<0.05) and exhibited thicker temporal and parietal CBM than the controls (temporal, P<0.05; parietal, P<0.001). The CBM thicknesses in the non-hemolytic anemia subgroup were similar to control values (P>0.05 for both). There were no correlations between age and CBM intensity or thickness, or between anemia severity and CBM intensity or thickness. CONCLUSION: Patients with chronic anemia exhibit lower CBM signal intensity on MRI than healthy subjects. Patients with hemolytic anemia have thicker CBM than patients with non-hemolytic anemia or healthy individuals. Decreased CBM intensity may indicate that the patient has anemia, and increased CBM thickness may specifically point to hemolytic anemia. These MRI findings may signal the need for further evaluation for the clinician.

Endoscopic removal of esthesioneuroblastoma.

Esthesioneuroblastoma is a rare tumor of neural crest origin that arises in the nasal cavity. There is still no consensus on the optimal treatment for this neoplasm, and the literature contains very few accounts of endoscopic excision in these cases. We described a case report of 12-year-old girl with esthesioneuroblastoma that was confined to the nasal cavity and paranasal sinuses, with no orbital or intracranial extension. The tumor was removed via intranasal endoscopic approach and radiotherapy was administered postoperatively. The patient is currently being followed, and there has been no recurrence in 24 months after surgery.

Investigation of hemodynamic changes after strabismus surgery using color Doppler imaging.

PURPOSE: To investigate hemodynamic changes after strabismus surgery using color Doppler imaging (CDI). METHOD: Group 1 patients (n = 13) underwent surgery on a single horizontal rectus muscle, and group 2 (n = 13) underwent surgery on both horizontal rectus muscles. Subjects with no systemic or ophthalmologic disorders were selected as controls (n = 16). In group 1 and group 2, CDI of the ophthalmic artery (OA), the central retinal artery (CRA), and the nasal and temporal posterior ciliary arteries (PCAs) was performed before surgical correction and on postoperative days 1 and 7. For each vessel, peak systolic (V(max)), end diastolic (V(min)), and mean (V(mean)) blood flow velocities were measured, in addition to the resistivity index (RI) and pulsatility index (PI). RESULTS: V(max) in the OA on postoperative day 1 was higher in group 2 than in group 1 (P =.004). V(min) in the OA on postoperative day 1 was significantly higher in group 2 than in the controls (P =.001) and group 1 (P =.001). For group 2, comparison of the OA preoperative findings to the findings on postoperative day 1 showed that V(min) (P =.003) and V(mean) (P =.02) increased significantly, and the RI (P =.01) and PI (P =.006) decreased significantly. These significant differences were not observed on day 7 (P >.05). CONCLUSION: Surgery on both horizontal rectus muscles in an eye causes hemodynamic changes in the OA in the early postoperative period.

Absent pulmonary valve syndrome diagnosed by fetal echocardiography.

Prenatal echocardiographic diagnosis of heart defects is important because it permits counseling of the parents with regard to prognosis and treatment options and prepares the medical team for the treatment postnatally. A male infant with absent pulmonary valve syndrome diagnosed prenatally at 22 weeks' gestation is reported. This congenital anomaly is characterized by absent or rudimentary pulmonary valve cusps, conoventricular septal defect, and massive dilatation of the pulmonary arteries. Soon after delivery the infant developed cyanosis and respiratory distress. The infant was placed in prone position for the relief of bronchial compression and nasal continuous positive airway pressure was (CPAP) started. Although the clinical status of the infant improved after supportive treatment, he deteriorated acutely and died at the age of five days. Fetal diagnosis remains an integral part of successful management of children with heart disease. Despite the potential benefits of prenatal diagnosis, it is hard to show significant improvement in mortality, especially in severely affected cases.

Endobronchial stenting in a two-month-old infant with bronchial compression secondary to tetralogy of Fallot and absent pulmonary valve.

Bronchial compression due to pulmonary artery dilation is an important problem in infants with congenital heart disease, and can complicate the postoperative course. In recent years, airway stenting has become a popular treatment for these cases. We achieved success with endobronchial stenting in a two-month-old infant with bronchial compression caused by a dilated pulmonary artery.

Bilateral calcifications in the basal ganglia, and frontal and parietal lobes of a patient with coeliac disease.

Previous authors have described a specific syndrome of coeliac disease, bilateral cerebral calcifications and epileptic seizures. We report a 4-year-old boy with coeliac disease who had bilateral calcifications in the basal ganglia and frontal and parietal lobes, but did not exhibit epileptic seizures.

Small bowel obstruction due to phytobezoar: CT diagnosis.

Small bowel phytobezoars are rare and are almost always obstructive. The literature contains few reports on the radiological findings for primary small bowel bezoars. There is also very little published on CT results with this lesion, but the features of the scan are characteristic. We present the CT findings in a patient with an obstructive small bowel phytobezoar, and emphasize the diagnostic value of CT.

Fat containing unusual tumor of the pancreas.

Fat-containing pancreatic tumors are very rare. In the literature, less than ten cases of lipoma originating from the pancreas have been reported. We present a case of pancreatic lipoma in a 65-year-old woman with findings of ultrasonography, computed tomography, and magnetic resonance imaging in addition to a brief review of the literature.

Roles of periosteum, dura, and adjacent bone on healing of cranial osteonecrosis.

It has been reported that large cranial osteonecrotic areas can heal. It was hypothesized that optimal healing is possible by the synchronized contribution of the osteogenic structures (periosteum, dura, and adjacent bone) that envelop the necrotic cranium. This hypothesis was tested by preserving or isolating the contribution of these osteogenic tissues. A total of 37 4-old-month rats were included in the study. Twelve animals were killed immediately, and cranial bone samples were taken and processed for examination (from 6 animals as fresh samples [Group A] and from the rest as autoclaved samples [Group B]). Group B was created to test if the bone was completely nonviable. In Group C (n = 25), cranial bone disks 8 mm in diameter were taken from 4-month-old rats, autoclaved, and put back onto the defect area. This group was further divided into the four Subgroups C1 through C4 (n = 7 in C3; n = 6 in C1, C2, and C4). Dura mater was isolated from the overlying bone disk with a polytetrafluoroethylene sheet in Subgroups C1 and C2, whereas the bone contacted the dura in the rest. The bone samples were covered with healthy periosteum in Subgroups C1 and C3 and with skin in Subgroups C3 and C4. These animals were killed after a healing period of 12 weeks, and the relevant bone disks were obtained. Surrounding healthy bone was also harvested from the same animals after they were killed to create Group D. The data of Group A and D were compared with those of the experimental group to comment on the degree of bone healing in the latter group. Quantitative and qualitative assessment was performed by mammography, bone densitometry, computed tomography, and histological examinations to find out the density and cellular content (osteocytes and vessels) of the samples. Examination of Group B samples showed nonviable tissue with a preserved microstructure. Analysis of other samples showed that both the periosteum and, mainly, the dura play an important role in cranial bone healing. The periosteal reaction was observed to be more evident when the dura was not separated. Cellular repopulation was more evident when both structures contributed to the healing process. Newly formed bone progressed centripetally; however, adjacent bone without the support of the dura and periosteum was capable of producing limited neovascularization and bone formation.