bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of matrix metalloproteinase and tissue inhibitor of MMP in methamphetamine‐induced behavioral sensitization and reward: implications for dopamine receptor down‐regulation and dopamine release
Authors: Mizoguchi Hiroyuki , Yamada Kiyofumi , Mouri Akihiro , Niwa Minae , Mizuno Tomoko , Noda Yukihiro , Nitta Atsumi , Itohara Shigeyoshi , Banno Yoshiko , Nabeshima Toshitaka 
Published: May 2007

AbstractMatrix metalloproteinases (MMPs) and its inhibitors (TIMPs) function to remodel the pericellular environment. We have demonstrated that methamphetamine (METH)‐induced behavioral sensitization and reward were markedly attenuated in MMP‐2‐ and MMP‐9 deficient [MMP‐2‐(−/−) and MMP‐9‐(−/−)] mice compared with those in wild‐type mice, suggesting that METH‐induced expression of MMP‐2 and MMP‐9 in the brain plays a role in the development of METH‐induced sensitization and reward. In the present study, we investigated the changes in TIMP‐2 expression in the brain after repeated METH treatment. Furthermore, we studied a role of MMP/TIMP system in METH‐induced behavioral changes and dopamine neurotransmission. Repeated METH treatment induced behavioral sensitization, which was accompanied by an increase in TIMP‐2 expression. Antisense TIMP‐2 oligonucleotide (TIMP‐AS) treatment enhanced the sensitization, which was associated with the potentiation of METH‐induced dopamine release in the nucleus accumbens (NAc). On the other hand, MMP‐2/‐9 inhibitors blocked the METH‐induced behavioral sensitization and conditioned place preference, a measure of the rewarding effect, and reduced the METH‐increased dopamine release in the NAc. Dopamine receptor agonist‐stimulated [35S]GTPγS binding was reduced in the frontal cortex of sensitized rats. TIMP‐AS treatment potentiated, while MMP‐2/‐9 inhibitor attenuated, the reduction of dopamine D2 receptor agonist‐stimulated [35S]GTPγS binding. Repeated METH treatment also reduced dopamine D2 receptor agonist‐stimulated [35S]GTPγS binding in wild‐type mice, but such changes were significantly attenuated in MMP‐2‐(−/−) and MMP‐9‐(−/−) mice. These results suggest that the MMP/TIMP system is involved in METH‐induced behavioral sensitization and reward, by regulating dopamine release and receptor signaling.
Deciphering adaptor specificity in GFL‐dependent RET‐mediated proliferation and neurite outgrowth
Authors: Gustin Jason A. , Yang Mao , Johnson Eugene M. , Milbrandt Jeffrey 
Published: May 2007

AbstractGlial cell derived neurotrophic factor (GDNF)‐dependent receptor tyrosine kinase RET activity is required for proper development of the nervous system and genitourinary tract. Loss‐of‐function mutations in RET are associated with enteric nervous system abnormalities (Hirschsprung disease) and renal deficits (Potter’s syndrome), whereas activating mutations lead to hereditary cancer syndromes (multiple endocrine neoplasia type 2A and type 2B). RET activation is crucial for the proper regulation of a variety of cellular processes including cell migration, proliferation and neurite outgrowth. By analyzing a series of RET mutants we found that Y1062 was critical for stimulating GDNF‐mediated proliferation as well as proliferation stimulated by GDNF‐independent oncogenic forms of RET. Studies using small interfering RNA driven by lentivirus to knock‐down expression of particular adaptor proteins that interact with RET phospho‐Y1062, demonstrated that only Src‐homology 2 and growth factor receptor binding protein 2 were necessary for RET‐mediated proliferation by wild type and oncogenic forms of RET. Interestingly, we discovered that Y1062 was also required for GDNF‐stimulated neurite outgrowth. However, small interfering RNAs to either Src‐homology 2 or growth factor receptor binding protein 2 or a panel of other adaptor proteins known to interact with RET Y1062 were incapable of blocking GDNF‐stimulated neurite formation, indicating that differential use of intracellular adaptors is responsible for regulating alternative RET‐stimulated cellular events such as proliferation versus a differentiation response like neurite outgrowth.
Calcium‐induced precipitate formation in brain mitochondria: composition, calcium capacity, and retention
Authors: Kristian Tibor , Pivovarova Natalia B. , Fiskum Gary , Andrews S. Brian 
Published: May 2007

AbstractBoth isolated brain mitochondria and mitochondria in intact neurons are capable of accumulating large amounts of calcium, which leads to formation in the matrix of calcium‐ and phosphorus‐rich precipitates, the chemical composition of which is largely unknown. Here, we have used inhibitors of the mitochondrial permeability transition (MPT) to determine how the amount and rate of mitochondrial calcium uptake relate to mitochondrial morphology, precipitate composition, and precipitate retention. Using isolated rat brain (RBM) or liver mitochondria (RLM) Ca2+‐loaded by continuous cation infusion, precipitate composition was measured in situ in parallel with Ca2+ uptake and mitochondrial swelling. In RBM, the endogenous MPT inhibitors adenosine 5′‐diphosphate (ADP) and adenosine 5′‐triphosphate (ATP) increased mitochondrial Ca2+ loading capacity and facilitated formation of precipitates. In the presence of ADP, the Ca/P ratio approached 1.5, while ATP or reduced infusion rates decreased this ratio towards 1.0, indicating that precipitate chemical form varies with the conditions of loading. In both RBM and RLM, the presence of cyclosporine A in addition to ADP increased the Ca2+ capacity and precipitate Ca/P ratio. Following MPT and/or depolarization, the release of accumulated Ca2+ is rapid but incomplete; significant residual calcium in the form of precipitates is retained in damaged mitochondria for prolonged periods.
Amyloid precursor protein intracellular domain modulates cellular calcium homeostasis and ATP content
Authors: Hamid Runa , Kilger Ellen , Willem Michael , Vassallo Neville , Kostka Markus , Bornhövd Carsten , Reichert Andreas S. , Kretzschmar Hans A. , Haass Christian , Herms Jochen 
Published: May 2007

AbstractConsecutive cleavages of amyloid precursor protein (APP) generate APP intracellular domain (AICD). Its cellular function is still unclear. In this study, we investigated the functional role of AICD in cellular Ca2+ homeostasis. We could confirm previous observations that endoplasmic reticulum Ca2+ stores contain less calcium in cells with reduced APP γ‐secretase cleavage products, increased AICD degradation, reduced AICD expression or in cells lacking APP. In addition, we observed an enhanced resting cytosolic calcium concentration under conditions where AICD is decreased or missing. In view of the reciprocal effects of Ca2+ on mitochondria and of mitochondria on Ca2+ homeostasis, we analysed further the cellular ATP content and the mitochondrial membrane potential. We observed a reduced ATP content and a mitochondrial hyperpolarisation in cells with reduced amounts of AICD. Blockade of mitochondrial oxidative phosphorylation chain in control cells lead to similar alterations as in cells lacking AICD. On the other hand, substrates of Complex II rescued the alteration in Ca2+ homeostasis in cells lacking AICD. Based on these observations, our findings indicate that alterations observed in endoplasmic reticulum Ca2+ storage in cells with reduced amounts of AICD are reciprocally linked to mitochondrial bioenergetic function.
Sympathetic predominance of cardiovascular regulation during mild orthostatic stress in adolescents with chronic fatigue
Authors: Wyller Vegard B. , Saul J. P. , Amlie Jan P. , Thaulow Erik 
Published: May 2007

SummaryHaemodynamic abnormalities have been documented in the chronic fatigue syndrome (CFS), indicating functional disturbances of the autonomic nervous system responsible for cardiovascular control. This study was designed to explore the pathophysiology in adolescent CFS‐patients by analysing RR‐interval (RRI) variability and diastolic blood pressure (DBP) variability during mild orthostatic stress, using an algorithm which accounts for non‐stationary biosignals. A total of 27 adolescents with CFS and 33 healthy control subjects having equal age‐ and sex distribution underwent 15 min of 20° head‐up tilt (HUT). The spectral power densities of RRI and DBP were computed in the low‐frequency (LF) band (0·04–0·15 Hz) and the high‐frequency (HF) band (0·15–0·4 Hz) using an adaptive autoregressive algorithm to obtain a time‐varying spectrum. RMSSD, a time domain index of RRI variability, was also computed. At rest, all indices of variability were similar in the two groups. During tilt, CFS patients had a larger increase in the LF/HF ratio (P≤0·001) and normalized LF power of RRI (P≤0·01), and a larger decrease in normalized HF power (P≤0·01) of RRI than controls. CFS patients also had trends towards a larger decrease in absolute HF power of RRI and a larger increase in normalized LF power of DBP. These findings suggest that adolescents with CFS have sympathetic predominance of cardiovascular regulation during very mild orthostatic stress. Possible underlying mechanisms are moderate hypovolemia, abnormalities of reflex control or physical de‐conditioning.
Neuromuscular and hormonal responses to a single session of whole body vibration exercise in healthy young men
Authors: Erskine Julie , Smillie Ian , Leiper John , Ball Derek , Cardinale Marco 
Published: May 2007

SummaryWhole body vibration (WBV) has been proposed as an alternative exercise stimulus to produce adaptive responses similar to resistance exercise. Few studies have analysed acute hormonal responses to WBV.Purpose  To evaluate neuromuscular and hormonal responses to an acute bout of isometric half‐squat exercise with and without superimposition of WBV.Methods  Seven healthy males (22·3 ± 2·7 years) performed 10 sets of half squat isometric exercise for 1 min with 1‐min rest between sets. Two separate trials were conducted either with WBV [30 Hz; 3·5 g (1 g = 9·81 m·s2)] or without vibration (Control). Salivary concentration of testosterone and cortisol was collected and maximal isometric unilateral knee extensions (MVC) were completed before, immediately after, 1, 2 and 24 h after treatment.Results  Significant decreases in MVC were observed immediately after (229·4 ± 53·2 Nm), 1 h (231·6 ± 59·9 Nm), and 2 h (233·0 ± 59·1 Nm) after WBV compared with baseline (252·7 ± 56·4 Nm; P<0·05). No significant change in MVC was recorded in Control. Rate of torque development in the first 200 ms (RTD200 ms), and salivary testosterone and cortisol concentrations were unaffected in both conditions. However, there was a trend for change over time in cortisol (P = 0·052), with an increase after WBV and decrease after Control.Conclusion  A 10 min session of intermittent WBV was shown to produce an acute reduction in MVC in healthy individuals, which recovered after 24 h. No significant changes were identified in salivary concentration of testosterone and cortisol suggesting that WBV with low acceleration does not represent a stressful stimulus for the neuroendocrine system.
Rash from Antiepileptic Drugs: Influence by Gender, Age, and Learning Disability
Authors: Alvestad Silje , Lydersen Stian , Brodtkorb Eylert 
Published: May 2007

Summary:  Purpose: Cutaneous adverse reactions from antiepileptic drugs (AEDs) are common, but have received little scientific attention from a clinical point of view. We wanted to study the incidence of skin reactions of current AEDs and to explore their relation to clinical parameters such as gender, age, and learning disability. Methods: Consecutive patients with epilepsy were studied retrospectively. A detailed survey of medical records concerning all treatment with AEDs was performed. Results: A total of 663 patients were included with altogether 2,567 exposures to 15 different AEDs. Skin reactions were found in 14% of the patients and in 5% of the exposures. Ninety‐seven percent of the reactions occurred to either carbamazepine (CBZ, 11%), phenytoin (PHT, 8%), lamotrigine (LTG, 8%), oxcarbazepine (8%), or phenobarbital (2%). Skin reactions developed significantly more often in females than in males (19% vs. 8%), and significantly less often in patients with learning disability than in other patients (7% vs. 16%). These differences were significant for CBZ, PHT, and LTG when analyzed separately. Females displayed higher rash frequency during the reproductive years, while men experienced less frequent rash in the same phase of life. Conclusions: Fertile females have a higher risk for skin reactions compared to males, probably due to hormonal factors. Patients with learning disability appeared to have a lower risk than other patients in this study. Hygiene factors may possibly be underlying.
The Natural History and Treatment of Epilepsy in a Murine Model of Tuberous Sclerosis
Authors: Erbayat‐Altay Ebru , Zeng Ling‐Hui , Xu Lin , Gutmann David H. , Wong Michael 
Published: May 2007

Summary:  Purpose: Patients with tuberous sclerosis complex (TSC) often have severe epilepsy that is intractable to available therapies. The development of novel treatments for epilepsy in TSC would benefit greatly from a suitable animal model, but most animal models of TSC to date have few reported neurological abnormalities, such as epilepsy. We previously described a novel model of TSC, due to conditional inactivation of the Tsc1 gene in glia (Tsc1GFAPCKO mice), in which mice develop epilepsy and premature death. Here, we characterize the natural history of the epilepsy in Tsc1GFAPCKO mice in more detail and report acute effects of treatment with standard antiepileptic drugs on seizures in these mice. Methods: Video‐EEG recordings were obtained from Tsc1GFAPCKO mice on a weekly basis, starting at 4 weeks of age until death, to monitor progression of interictal EEG abnormalities and seizures. In separate experiments, Tsc1GFAPCKO mice were monitored for interictal EEG abnormalities and seizures before and during treatment with phenobarbital, phenytoin, or saline. Results: Tsc1
GFAPCKO mice developed seizures around 4–6 weeks of age and subsequently had progressive worsening of the interictal EEG background and seizure frequency over a month, culminating in death. Treatment with phenobarbital or phenytoin caused a reduction in seizure frequency, but did not improve EEG background or prevent death. Conclusions: Tsc1
GFAPCKO mice develop progressive epilepsy. Acute treatment with standard antiepileptic drugs suppresses seizures in these mice, but does not affect long‐term prognosis. Tsc1GFAPCKO mice represent a good model to test other drugs that may have true antiepileptogenic actions in TSC.
Epilepsy in Phenylketonuria: A Complex Dependence on Serum Phenylalanine Levels
Authors: Martynyuk Anatoly E. , Ucar Deniz A. , Yang Dawn D. , Norman Wendy M. , Carney Paul R. , Dennis Donn M. , Laipis Philip J. 
Published: May 2007

Summary:  Purpose: Phenylketonuria (PKU) is a disorder of phenylalanine (Phe) metabolism that frequently results in epilepsy if a low Phe diet was not implemented at birth. The mechanisms by which Phe affects the brain are poorly understood. Methods: Audiogenic seizures (AGS) were studied in female homozygous Pahenu2 BTBR (PKU) mice. Results: Adult PKU mice, 18–20 weeks of age, in contrast to wild‐type and heterozygous counterparts, exhibited a full range of AGS. Younger PKU mice, 5–7 weeks of age, had higher serum Phe levels (2.22 ± 0.20 mM) in comparison with the adult animals (1.72 ± 0.05 mM) and were not susceptible to AGS. Among adult mice, animals susceptible to AGS had significantly lower serum Phe levels (1.62 ± 0.06 mM) in comparison with those resistant to AGS (1.86 ± 0.07 mM). Susceptibility to AGS tended to increase in the afternoon when serum Phe concentration decreased in comparison to evening and morning. Normalization of serum Phe level by instituting a low Phe diet generally prevented susceptibility to AGS within 12 h. Although return to a standard diet raised Phe levels to hyperphenylalaninemic within 12 h in animals treated with a low Phe diet for 2 weeks, more than 7 weeks were needed for a complete resumption of AGS. Conclusions: Transient decrease in Phe levels within hyperphenylalaninemic range may be a necessary condition for PKU‐related seizures to occur. A low Phe diet prevents susceptibility to seizures, which can resume with the significant delay after termination of dietary treatment.
Typical versus Atypical Absence Seizures: Network Mechanisms of the Spread of Paroxysms
Authors: Velazquez Jose L. Perez , Huo Jeanne Zhen , Dominguez L. Garcia , Leshchenko Yevgen , Snead III O. Carter 
Published: May 2007

Summary: Purpose:Typical absence seizures differ from atypical absence seizures in terms of semiology, EEG morphology, network circuitry, and cognitive outcome, yet have the same pharmacological profile. We have compared typical to atypical absence seizures, in terms of the recruitment of different brain areas. Our initial question was whether brain areas that do not display apparent paroxysmal discharges during typical absence seizures, are affected during the ictal event in terms of synchronized activity, by other, distant areas where seizure activity is evident. Because the spike‐and‐wave paroxysms in atypical absence seizures invade limbic areas, we then asked whether an alteration in inhibitory processes in hippocampi may be related to the spread seizure activity beyond thalamocortical networks, in atypical seizures.Methods:We used two models of absence seizures in rats: one of typical and the other of atypical absence seizures. We estimated phase synchronization, and evaluated inhibitory transmission using a paired‐pulse paradigm.Results:In typical absence seizures, we observed an increase in synchronization between hippocampal recordings when spike‐and‐wave discharges occurred in the cortex and thalamus. This indicates that seizure activity in the thalamocortical circuitry enhances the propensity of limbic areas to synchronize, but is not sufficient to drive hippocampal circuitry into a full paroxysmal discharge. Lower paired‐pulse depression was then found in hippocampus of rats that displayed atypical absence seizures.Conclusions:These observations suggest that circuitries in brain areas that do not display apparent seizure activity become synchronized as seizures occur within thalamocortical circuitry, and that a weakened hippocampal inhibition may predispose to develop synchronization into full paroxysms during atypical absence seizures.
Interobserver Reliability of Video Recording in the Diagnosis of Nocturnal Frontal Lobe Seizures
Authors: Vignatelli Luca , Bisulli Francesca , Provini Federica , Naldi Ilaria , Pittau Francesca , Zaniboni Anna , Montagna Pasquale , Tinuper Paolo 
Published: May 2007

Summary:  Background: Nocturnal frontal lobe seizures (NFLS) show one or all of the following semeiological patterns: (1) paroxysmal arousals (PA: brief and sudden recurrent motor paroxysmal behavior); (2) hyperkinetic seizures (HS: motor attacks with complex dyskinetic features); (3) asymmetric bilateral tonic seizures (ATS: motor attacks with dystonic features); (4) epileptic nocturnal wanderings (ENW: stereotyped, prolonged ambulatory behavior). Objective: To estimate the interobserver reliability (IR) of video‐recording diagnosis in patients with suspected NFLS among sleep medicine experts, epileptologists, and trainees in sleep medicine. Methods: Sixty‐six patients with suspected NFLS were included. All underwent nocturnal video‐polysomnographic recording. Six doctors (three experts and three trainees) independently classified each case as “NFLS ascertained” (according to the above specified subtypes: PA, HS, ATS, ENW) or “NFLS excluded”. IR was calculated by means of Kappa statistics, and interpreted according to the standard classification (0.0–0.20 = slight agreement; 0.21–0.40 = fair; 0.41–0.60 = moderate; 0.61–0.80 = substantial; 0.81–1.00 = almost perfect). Results: The observed raw agreement ranged from 63% to 79% between each pair of raters; the IR ranged from “moderate” (kappa = 0.50) to “substantial” (kappa = 0.72). A major source of variance was the disagreement in distinguishing between PA and nonepileptic arousals, without differences in the level of agreement between experts and trainees. Conclusions: Among sleep experts and trainees, IR of diagnosis of NFLS, based on videotaped observation of sleep phenomena, is not satisfactory. Explicit video‐polysomnographic criteria for the classification of paroxysmal sleep motor phenomena are needed.
Selective inhibition of prostacyclin synthase activity by rofecoxib
Authors: Griffoni Cristiana , Spisni Enzo , Strillacci Antonio , Toni Mattia , Bachschmid Markus Michael , Tomasi Vittorio 
Published: May 2007

AbstractThe development of cyclooxygenase‐2 (COX‐2) selective inhibitors prompted studies aimed at treating chronic inflammatory diseases and cancer by using this new generation of drugs.Yet, several recent reports pointed out that long‐term treatment of patients with COX‐2 selective inhibitors (especially rofecoxib) caused severe cardiovascular complicances. The aim of this study was to ascertain whether, in addition to inhibiting COX‐2, rofecoxib may also affect prostacyclin (PGI2) level by inhibiting PGI2 forming enzyme (prostacyclin synthase, PGIS). In order to evaluate if selective (celecoxib, rofecoxib) and non‐selective (aspirin, naproxen) anti‐inflammatory compounds could decrease PGI2 production in endothelial cells by inhibiting PGIS, we analyzed the effect of anti‐inflammatory compounds on the enzyme activity by ELISA assay after addition of exogenous substrate, on PGIS protein levels by Western blotting and on its subcellular distribution by confocal microscopy. We also analyzed the effect of rofecoxib on PGIS activity in bovine aortic microsomal fractions enriched in PGIS. This study demonstrates an inhibitory effect of rofecoxib on PGIS activity in human umbilical vein endothelial (HUVE) cells and in PGIS‐enriched bovine aortic microsomal fractions, which is not observed by using other anti‐inflammatory compounds. The inhibitory effect of rofecoxib is associated neither to a decrease of PGIS protein levels nor to an impairment of the enzyme intracellular localization. The results of this study may explain the absence of a clear relationship between COX‐2 selectivity and cardiovascular side effects. Moreover, in the light of these results we propose that novel selective COX‐2 inhibitors should be tested on PGI2 synthase activity inhibition.
Roles of CD147 on T lymphocytes activation and MMP‐9 secretion in Systemic Lupus Erythematosus
Authors: Pistol Gina , Matache Cristiana , Calugaru Ana , Stavaru Crina , Tanaseanu Stefanita , Ionescu Ruxandra , Dumitrache Sergiu , Stefanescu Maria 
Published: May 2007

AbstractThe cellular and molecular mechanisms involved in many abnormalities described in Systemic Lupus Erythematosus (SLE) are still unclear. Some of these abnormalities referred to the hyperactivation of T lymphocytes and the enhanced secretion of MMP‐9 by peripheral blood mononuclear cells (PBMCs). Therefore, in this paper we investigated the potential role of CD147 molecule in these abnormalities. Our results demonstrated that CD147 molecule is overexpressed on CD3+T lymphocytes from SLE patients when compared with CD3+T lymphocytes from healthy donors. Monoclonal anti‐CD147 antibodies, MEM‐M6/1 clone, were able to inhibit protein tyrosine phosphorylation only in CD3 × CD28 costimulated T lymphocytes from SLE patients. However, this monoclonal antibody was unable to inhibit the enhanced activity of MMP‐9 secreted by SLE PBMCs.