Clinical Neuroscience

[Editor’s note]

RAJNA Péter

MARCH 20, 2007

Clinical Neuroscience - 2007;60(03-04)

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Clinical Neuroscience

[GLUTAMATERGIC PHENOTYPE OF HYPOTHALAMIC NEUROSECRETORY SYSTEMS: A NOVEL ASPECT OF CENTRAL NEUROENDOCRINE REGULATION]

HRABOVSZKY Erik, LIPOSITS Zsolt

[While three decades ago, the co-existence of classical neurotransmitters and peptide neuromodulators in a single neuronal cell was considered to be rather exceptional, the phenomenon that neurons have a complex transmitter phenotype now appears to be the general rule. Parvicellular and magnocellular neurosecretory systems consist of neuronal cells which are specialized in secreting peptide neurohormones into the blood-stream to regulate hypophyseal functions. This mini-review, dedicated to the memory of Mariann Fodor, summarizes the current knowledge about the classical neurotransmitter content of different hypothalamic neurosecretory systems, with a special focus on the occurrence and putative functions of glutamate in parvicellular and magnocellular neurosecretory cells.]

Clinical Neuroscience

[BRAIN INSULIN SIGNALLING IN THE REGULATION OF ENERGY BALANCE AND PERIPHERAL METABOLISM]

MICHAELA Diamant

[The unparalleled global rates of obesity and type 2 diabetes, together with the associated cardiovascular morbidity and mortality, are referred to as the "diabesity pandemic". Changes in lifestyle occurring worldwide, including the increased consumption of high-caloric foods and reduced exercise, are regarded as the main causal factors. Central obesity and insulin resistance have emerged as important linking components. Understanding the aetiology of the cluster of pathologies that leads to the increased risk is instrumental in the development of preventive and therapeutic strategies. Historically, skeletal muscle, adipose tissue and liver were regarded as key insulin target organs involved in insulinmediated regulation of peripheral carbohydrate, lipid and protein metabolism. The consequences of impaired insulin action in these organs were deemed to explain the functional and structural abnormalities associated with insulin resistance. The discovery of insulin receptors in the central nervous system, the detection of insulin in the cerebrospinal fluid after peripheral insulin administration and the well-documented effects of intracerebroventricularly injected insulin on energy homeostasis, have identified the brain as an important target for insulin action. In addition to its critical role as a peripheral signal integrating the complex network of hypothalamic neuropeptides and neurotransmitters that influence parameters of energy balance, central nervous insulin signalling is also implicated in the regulation of peripheral glucose metabolism. This review summarizes the evidence of insulin action in the brain as part of the multifaceted circuit involved in the central regulation of energy and glucose homeostasis, and discuss the role of impaired central nervous insulin signalling as a pathogenic factor in the obesity and type 2 diabetes epidemic.]

Clinical Neuroscience

[POSTNATAL EXPRESSION PATTERN OF DOUBLECORTIN (DCX) IN SOME AREAS OF THE DEVELOPING BRAIN OF MOUSE]

TAKÁCS József, ROBERTA Zaninetti, VÍG Julianna, VASTAGH Csaba, HÁMORI József

[We have investigated the spatio-temporal expression pattern of doublecortin (DCX) protein from postnatal day (P) 2 to postnatal day (P) 22 in the brain of developing mouse. We compared the expression of DCX in the rostral migratory stream (RMS) and dentate gyrus of the hippocampus (DG). Weak expression of DCX was detected in the RMS at P5, it became gradually stronger during the second postnatal week and reached its strongest expression by P18-P22. Moderate DCX immunostaining was present in the DG at P11, its marked expression - characteristic of newly generated neurons in the adult DG - appeared only after P22. Morphological and functional maturation was different in the RMS and DG, continuous neurogenesis appeared earlier in the RMS than in the DG.]

Clinical Neuroscience

[IMMOBILIZATION INDUCED FOS EXPRESSION IN THE MEDIAL AND LATERAL HYPOTHALAMIC AREAS: A LIMITED RESPONSE OF HYPOCRETIN NEURONS]

KISS Alexander

[Induction of Fos, a proto-oncogene c-fos protein product, was immunohistochemically examined in the rat hypothalamic neurons 3 h after a single (1×120 min) or repeated (7×120 min) immobilization (IMO) stress. The aim of the present study was to reveal a possible parallelism in the cell activation between the medial and lateral hypothalamic neurons, especially between the stress responsive neurons in the hypothalamic paraventricular nucleus (PVN) and hypocretin (Hcrt) synthesizing neurons, i.e. suspected stress active neurons of the lateral hypothalamus. After IMO, the animals were perfused and their brains processed with immunohistochemistry for Fos or Fos/Hcrt proteins. Acute IMO elicited extensive Fos expression in both the examined areas. Excessive Fos expression was mainly seen in the PVN, while Hcrt neurons failed to show a broad response (appr. 5%) to single IMO. Clear occurrence of Fos signal was also seen in both hypothalamic areas of IMO-habituated rats. However, in these animals, in both areas examined, the number of Fos neurons was considerably suppressed, including the PVN. These results indicate that IMO is able to evoke a concurrent activation of Fos in many medial and lateral hypothalamic neurons. However, the scanty response of Hcrt neurons to acute IMO does not allow to assort them to a distinct IMO stress-responsive neuronal phenotypes of the brain.]

Clinical Neuroscience

[PROTECTIVE ACTION OF SNAKE VENOM NAJA NAJA OXIANA AT SPINAL CORD HEMISECTION]

ABRAHAMYAN S. Silva, MELIKSETYAN B. Irina, CHAVUSHYAN A. Vergine, ALOYAN L. Mery, SARKISSIAN S. John

[Based on data accumulated regarding the neuroprotective action of Proline-Rich-Peptide-1 (PRP-1, a fragment of neurophysin vasopressin associated hypothalamic glycoprotein consisting of 15 amino acid residues) on neurons survival and axons regeneration and taking into the account that LVV-Hemorphin-7 (LVV-H7, an opioid peptide, widely distributed in different cell types of various tissues of intact rats, including those of the nervous and immune systems) derived from the proteolitic processing of hemoglobin in response to adverse environmental and physiological conditions, possesses the anti-stressor properties, we used histochemistry, immunohistochemistry and electrophysiology to investigate the putative neuroprotective action of Central Asian Cobra Naja naja oxiana snake venom (NOX) on trauma-injured rats. ABC immunohistochemical method and histochemical method on detection of Ca2+- dependent acid phosphatase activity were used for the morpho-functional study. By recording the electrical activity of the signals from the single neurons in and below the SC injury place, NOX venom has been shown to result in the complete restoration of hypothalamic-spinal projections originated from ipsi- and contra-lateral PVN and SON to neurons of SC lumbar part. NOX prevented the scar formation, well observed two months after SC injury in the control rats, resulted in the regeneration of nerve fibers growing through the trauma region, survival of the PRP-1- and LVV-H7-immunoreactive (Ir) neurons, and increase of the PRP-1- and LVV-H7-Ir nerve fibers and astrocytes in the SC lesion region. NOX was suggested to exert the neuroprotective effect, involving the PRP-1 and LVV-H7 in the underlying mechanism of neuronal recovery.]

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[The authors review the time of 10 years between 2005-2014 concerning the development of the mortality rate of kidney diseases in Hungary. They’ve compared the Hungarian mortality data with the ones from three other countries, namely Austria, the Czech Republic and Germany. The analyses included kidney diseases originated from hypertension, glomerulonephritis and tubulointerstitial kidney diseases, kidney failure and polycystic kidney diseases. They weren’t concerned about kidney tumors or diabetes originated kidney diseases because of the lack of data concerning the latter. The mortality data were retrieved from the KSH Demography Yearbook and the European Detailed Mortality Data-base (DMDB). The statistically examined causes of death only add up to 1.2% of the total causes of death, but with the aging of the population this proportion will surely grow. During the last 10 years, the mortality of cardiovascular diseases decreased significantly, namely the mortality of ischaemic heart disease and stroke, but the mortality of hypertension increased. These processes can also be seen in Austria, the Czech Republic and Germany. The mortality connected to primal kidney diseases decisively concerns people aged over 70. The glomerular diseases’ standardized rate is significantly higher in Hungary than in the compared countries. The tubulointerstitial kidney diseases’ mortality rate decreased over the last 10 years and we are in the middle of the international field in this regard. During the evaluation of the mortality of kidney diseases it is important to consider that in the statistics every death can only have one cause nominated, which can be (correctly) the basic disease causing the kidney disease or in other cases the kidney disease itself. This problem makes it more difficult to compare data internationally. Only 20-30 patients die of acute kidney disease on a yearly basis which is a low mortality rate even by international standards but the above-mentioned problem still exists. Of all of them the chronic kidney disease is the most significant one and between 2005-2014 the number of deaths and their rate connected to it decreased, but with the aging of the population the morbidity of kidney diseases will surely increase. Analyzing the data of all the primer kidney diseases it can be determined that between 2005-2014 the mortality rate showed a decreasing tendency, so our international situation can be viewed positively. It is important to note though that the mortality of this disease type includes patients of lower average age in Hungary than in the more developed countries. The mortality rate of polycystic kidney disease hasn’t changed significantly during the past 10 years. Although some patients live to many years, the average age of the dead is significantly lower compared to the ones of other kidney disease types. The cases below the age of 1 year of the latter add up to 10%. The comparison between the countries concerning the po­lycystic kidney disease shows that the standardized mortality rate is higher in Hun­gary.]

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[THE LONG ACTING INSULIN ANALOGUE DETEMIR IN THE DIABETOLOGICAL PRACTICE: EVIDENCE AND POTENTIALS]

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[Insulin detemir is a neutral, soluble, long-acting insulin analogue in which the amino acid threonineB30 has been removed and the LysB29 acylated with a 14-carbon fatty acid. The fatty acid modification allows insulin detemir to dihexamerisate and reversibly bind to human albumin upon administration. This brand new principle (self association and albumin binding) ensures slow absorption and a prolonged and consistent metabolic effect without a marked peak for up to 24 hours in patients both with type 1 and type 2 diabetes mellitus. Results of large clinical trials have shown that detemir can be efficiently used as basal insulin, supplemented with human regular insulin or aspart insulin taken before the main meals, in both type 1 and type 2 diabetes. Available data clearly demonstrate that the use of this insulin is associated with decreased variability of the fasting blood glucose values. In some of the studies the risk of (mostly nocturnal) hypoglycaemic episodes also dropped. It is important to note that patients using insulin detemir gained less or no weight compared to the group of patients treated with neutral protamine Hagedorn (NPH) insulin. Evaluation of long-term and wide-spread application of detemir needs further observations. Such trials are being conducted worldwide.]