Immunfehérjék akcióban

2012-t az UNESCO Szentágothai emlékévvé nyilvánította. A legendás neuroanatómus és egyetemi tanár emléke előtt tisztelegve egy olyan vizsgálati technikát mutatunk be, amelynek segítségével láthatóvá és megérthetővé válhatnak a Szentágothai János kutatásának is középpontjában álló neuronális hálózatok, azok funkcionális anatómiája

Anatomical Distribution of Nucleoside System in the Human Brain and Implications for Therapy

Nucleosides have a wide range of physiological and pathophysiological roles in the human brain as modulators of a variety of neural functions. For example, adenosine, inosine, guanosine, and uridine participate in the mechanisms underlying memory, cognition, sleep, pain, depression, schizophrenia, epilepsy, Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease. Consequently, increasing attention is now being given to the speci fi c role of nucleosides in physiological and pathological processes in the human brain. Different elements of nucleoside system, including nucleoside concentrations, metabolic enzyme activity, and expression of nucleoside transporters and receptors, may be changed under normal and pathological conditions. The alterations suggest that interlinked elements of the nucleoside system are functioning in a tightly concerted manner. Nucleoside levels, activity of nucleoside metabolic enzymes, and expression of nucleoside transporters and receptors are unevenly distributed in the brain, suggesting that nucleosides have different roles in functionally distinct human brain areas. The aim of this chapter is to summarize our present knowledge of the anatomical distribution of nucleoside system in the human brain, placing emphasis on potential therapeutic pharmacological strategies

Az utódgondozás idegrendszeri szabályozása : Az anyai agy

Az emlősállatok nőstény egyedei hatalmas megterhelésnek vannak kitéve a szaporodás során, hiszen - fajtól függő mértékben ugyan, de - elsősorban rájuk hárul az utódok táplálása és gondozása. Egy, az anyasággal bekövetkező változásokban szerepet játszó, rövid fehérje típusú idegrendszeri szabályozó molekula, úgynevezett neuropeptid felfedezését írja le következő, az OTKA-Élet és Tudomány közös cikkpályázatára beküldött cikkünk

Preoptic Inputs and Mechanisms that Regulate Maternal Responsiveness

The preoptic area is a well-established centre for the control of maternal behaviour. An intact medial preoptic area (mPOA) is required for maternal responsiveness because lesion of the area abolishes maternal behaviours. Although hormonal changes in the peripartum period contribute to the initiation of maternal responsiveness, inputs from pups are required for its maintenance. Neurones are activated in different parts of the mPOA in response to pup exposure. In the present review, we summarise the potential inputs to the mPOA of rodent dams from the litter that can activate mPOA neurones. The roles of potential indirect effects through increased prolactin levels, as well as neuronal inputs to the preoptic area, are described. Recent results on the pathway mediating the effects of suckling to the mPOA suggest that neurones containing the neuropeptide tuberoinfundibular peptide of 39 residues in the posterior thalamus are candidates for conveying the suckling information to the mPOA. Although the molecular mechanism through which these inputs alter mPOA neurones to support the maintenance of maternal responding is not yet known, altered gene expression is a likely candidate. Here, we summarise gene expression changes in the mPOA that have been linked to maternal behaviour and explore the idea that chromatin remodelling during mother-infant interactions mediates the long-term alterations in gene expression that sustain maternal responding

Transzformáló növekedési faktor béta fehérjék a központi idegrendszerben = Transforming growth factor beta proteins in the central nervous system

A három TGF-béta altípus agyban való eloszlása specifikus, vagyis elkülönült idegrendszeri funkcióik lehetnek. A TGF-béta1 magas expressziót mutatott a hypothalamusz preoptikus területén, ahol eloszlása hasonló volt azonosított anyai neuropeptidekéhez. Ez arra utal, hogy a TGF-béta1 szerepet játszhat az idegrendszer anyai adaptációiban. Emellett a TGF-béta rendszer elemeit azonosítottuk a laterális hypothalamus orexin sejtjeiben is. A TGF-béta fehérjék neuroprotektív folyamatokban való részvételét is vizsgáltuk. Fokális agyi ischaemiát idéztünk elő az egyik középső agyi artéria okklúziójával. Ennek hatására TGF-béta1 indukálódott a lézió körüli penumbrában. A TGF-béta2 és 3 expressziója viszont máshol, az azonos oldali agykéreg II, III, és V. rétegének teljes hosszában növekedett meg. A TGF-béta1 együttes expressziót mutatott az ATF-3-al, míg a TGF-béta2 és 3 Fos fehérjét kifejező sejtekben indukálódott. Egyik neurontípus sem festődött Fluoro Jade C-vel, egy neurodegenerációt jelző markerrel. Eredményeink arra utalnak, hogy az endogen TGF-béta fehérjék részt vehetnek neuroprotektív funkciókban, de ischaemiás eseményt követően eltérő mechanizmussal indukálódnak. Szintén megvizsgáltuk a TGF-béta rendszert a TGF-béta kötőfehérje 1 hiányában knock-out egérben, és jelentős változást nem tapasztaltunk. Összességében elmondhatjuk, hogy a pályázat keretében szerzett új ismereteknek jelentős szerepe van az agy TGF-béta rendszerének megértésében, és a rendszer jövőbeli kihasználásában ischaemiás stroke-ot követően. | The topographical distribution of mRNAs of the 3 TGF-betas in the brain were characteristic of the particular type of TGF-beta suggesting that they play a role in separate brain functions. TGF-beta1 was abundantly expressed in the preoptic area of the hypothalamus with a distribution similar to identified maternal neuropeptides in the region suggesting that TGF-beta1 may play a role in maternal adaptations. We also identified elements of the TGF-beta system in orexin neurons of the lateral hypothalamus. The involvement of TGF-betas in neuroprotection has also been established. Focal brain ischemia was induced with unilateral occlusion of the middle cerebral artery. TGF-beta1 was induced in the penumbra around the lesion. The expression of TGF-beta2 and 3 was increased in layers II, III, and V of the ipsilateral cerebral cortex. TGF-beta1 was co-localized with ATF-3 while TGF-beta2 appeared in Fos-expressing cells. In turn, these neurons did not contain Fluoro Jade C, a marker of neurodegeneration. Thus, endogenous TGF-betas may participate in neuroprotection, although they are induced by different mechanisms following an ischemic attack. We also examined the TGF-beta system in the absence of TGF-beta binding protein 1 in knock-out mice and found no major effects. Collectively, the new knowledge gained in the framework of the proposal is expected to have a major positive impact on understanding the TGF-beta system in the central nervous system and its utilization to alleviate the consequences of ischemic stroke

Lipopolysaccharide induced increase in seizure activity in two animal models of absence epilepsy WAG/Rij and GAERS rats and Long Evans rats

We showed previously that the number and time of spike-wave discharges (SWDs) were increased after intraperitoneal (i.p.) injection of lipopolysaccharide (LPS), an effect, which was completely abolished by cyclooxygenase-2 (COX-2) inhibitor indomethacin (IND) pretreatment in Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. These and other results suggest that injection of LPS to genetically absence epileptic animals, such as WAG/Rij rats, may allow us to investigate relationships between absence epilepsy and LPS evoked neuroinflammation processes. However, LPS may evoke different effects on absence epileptic activity in various animal strains. Thus, to extend our previous results, we injected two doses of LPS (50 μg/kg and 350 μg/kg i.p.) alone and in combination with IND (10mg/kg IND i.p. +50 μg/kg LPS) into rats of two model animal strains (WAG/Rij rats; GAERS rats: Genetic Absence Epileptic Rats from Strasbourg) and into Long Evans rats. The effects of treatments on SWD number and SWD duration were examined. Both doses of LPS increased the SWD number and the total time of SWDs dose-dependently during the whole 4-h recording period, which was abolished by IND pretreatment in all three investigated strains. These results extend our previous results suggesting that our methods using LPS injection into freely moving absence epileptic rats is applicable not only in well-established animal models of absence epilepsy such as WAG/Rij rats and GAERS rats but also in Long Evans rats to investigate links between inflammation and absence epilepsy

5'-nucleotidases, nucleosides and their distribution in the brain: pathological and therapeutic implications

Elements of the nucleoside system (nucleoside levels, 5'-nucleotidases (5'NTs) and other nucleoside metabolic enzymes, nucleoside transporters and nucleoside receptors) are unevenly distributed in the brain, suggesting that nucleosides have region-specific functions in the human brain. Indeed, adenosine (Ado) and non-Ado nucleosides, such as guanosine (Guo), inosine (Ino) and uridine (Urd), modulate both physiological and pathophysiological processes in the brain, such as sleep, pain, memory, depression, schizophrenia, epilepsy, Huntington's disease, Alzheimer's disease and Parkinson's disease. Interactions have been demonstrated in the nucleoside system between nucleoside levels and the activities of nucleoside metabolic enzymes, nucleoside transporters and Ado receptors in the human brain. Alterations in the nucleoside system may induce pathological changes, resulting in central nervous system (CNS) diseases. Moreover, several CNS diseases such as epilepsy may be treated by modulation of the nucleoside system, which is best achieved by modulating 5'NTs, as 'NTs exhibit numerous functions in the CNS, including intracellular and extracellular formation of nucleosides, termination of nucleoside triphosphate signaling, cell adhesion, synaptogenesis and cell proliferation. Thus, modulation of 5'NT activity may be a promising new therapeutic tool for treating several CNS diseases. The present article describes the regionally different activities of the nucleoside system, demonstrates the associations between these activities and 5'NT activity and discusses the therapeutic implications of these associations