Neuroscience Unit

Liverpool, United Kingdom

Neuroscience Unit

Liverpool, United Kingdom
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Al Sweidi S.,Laval University | Al Sweidi S.,Neuroscience unit | Morissette M.,Neuroscience unit | Rouillard C.,Neuroscience unit | And 3 more authors.
Neuroscience | Year: 2013

Neuroprotection by 17β-estradiol and an estrogen receptor (ER) agonist against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesion were shown to implicate protein kinase B (Akt) signaling in mice. In order to evaluate the associated mechanisms, this study compared estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) intact or knockout (KO) and wild-type (WT) C57Bl/6 male mice following MPTP treatment of 7, 9, 11mg/kg and/or 17β-estradiol. Striatal D1 and D2 dopamine (DA) receptors were measured by autoradiography with the specific ligands [3H]-SCH 23390 and [3H]-raclopride, respectively and signaling by Western blot for Akt, glycogen synthase kinase 3β (GSK3β) and extracellular-regulated signal kinases (ERK1 and ERK2). Control ERKOβ mice had lower striatal [3H]-SCH 23390 specific binding than WT and ERKOα mice; both KO mice had lower [3H]-raclopride specific binding. Striatal D1 receptors decreased with increasing doses of MPTP in correlation with striatal DA concentrations in ERKOα mice and remained unchanged in WT and ERKOβ mice. Striatal D2 receptors decreased with increasing doses of MPTP in correlation with striatal DA concentrations in WT and ERKOα mice and increased in ERKOβ mice. In MPTP-lesioned mice, 17β-estradiol treatment increased D1 receptors in ERKOα and ERKOβ mice and D2 receptors in WT and ERKOβ mice. MPTP did not affect striatal pAkt/Akt and pGSK3β/GSK3β levels in WT and ERKOα mice, while in vehicle-treated ERKOβ mice these levels were higher and increased with MPTP lesioning. Striatal pERK1/ERK1 and pERK2/ERK2 levels showed to a lesser extent a similar pattern. In conclusion, ERs affected the response of striatal DA receptors to a MPTP lesion and post receptor signaling. © 2013 IBRO.

Zibara K.,Lebanese University | El Zein N.,Lebanese University | Sabra M.,Lebanese University | Hneino M.,Lebanese University | And 5 more authors.
Frontiers in Neurology | Year: 2017

Thyroxine (T4) enters the brain either directly across the blood-brain barrier (BBB) or indirectly via the choroid plexus (CP), which forms the blood-cerebrospinal fluid barrier (B-CSF-B). In this study, using isolated perfused CP of the sheep by single-circulation paired tracer and steady-state techniques, T4 transport mechanisms from blood into lateral ventricle CP has been characterized as the first step in the transfer across the B-CSF-B. After removal of sheep brain, the CPs were perfused with 125I-T4 and 14C-mannitol. Unlabeled T4 was applied during single tracer technique to assess the mode of maximum uptake (Umax) and the net uptake (Unet) on the blood side of the CP. On the other hand, in order to characterize T4 protein transporters, steady-state extraction of 125I-T4 was measured in presence of different inhibitors such as probenecid, verapamil, BCH, or indomethacin. Increasing the concentration of unlabeled-T4 resulted in a significant reduction in Umax%, which was reflected by a complete inhibition of T4 uptake into CP. In fact, the obtained Unet% decreased as the concentration of unlabeled-T4 increased. The addition of probenecid caused a significant inhibition of T4 transport, in comparison to control, reflecting the presence of a carrier mediated process at the basolateral side of the CP and the involvement of multidrug resistance-associated proteins (MRPs: MRP1 and MRP4) and organic anion transporting polypeptides (Oatp1, Oatp2, and Oatp14). Moreover, verapamil, the P-glycoprotein (P-gp) substrate, resulted in ~34% decrease in the net extraction of T4, indicating that MDR1 contributes to T4 entry into CSF. Finally, inhibition in the net extraction of T4 caused by BCH or indomethacin suggests, respectively, a role for amino acid "L" system and MRP1/Oatp1 in mediating T4 transfer. The presence of a carrier-mediated transport mechanism for cellular uptake on the basolateral membrane of the CP, mainly P-gp and Oatp2, would account for the efficient T4 transport from blood to CSF. The current study highlights a carrier-mediated transport mechanism for T4 movement from blood to brain at the basolateral side of B-CSF-B/CP, as an alternative route to BBB. © 2017 Zibara, Zein, Sabra, Hneino, Harati, Mohamed, Kobeissy and Kassem.

Livingston J.,Leeds General Infirmary | Doherty D.,University of Washington | Orcesi S.,Irccs C Mondino Institute Of Neurology Foundation | Tonduti D.,Irccs C Mondino Institute Of Neurology Foundation | And 8 more authors.
Neuropediatrics | Year: 2011

Introduction: Intracranial calcification (ICC) is a relatively common radiological finding in children undergoing investigation for neurological disorders. Many causes are recognised, and ICC is often regarded as a non-specific sign. Methods: From an ongoing study of ICC, we identified 5 patients with characteristic radiological features, in whom a mutation in the COL4A1 gene was found. Results: All patients had CT and MR imaging. MR images demonstrated features of periventricular leukomalacia with irregular dilatation of the lateral ventricles with or without porencephaly, loss of hemispheric white matter volume, and high signal on T2 and FLAIR sequences within periventricular and deep white matter. Calcification was apparent on MR in 4 patients. CT scans demonstrated spot and linear calcification in the subependymal region and around areas of porencephaly. Calcification was also visible in the deep cerebral white matter and basal ganglia. 1 patient showed calcification in the central pons. Conclusion: ICC occurs in COL4A1-related disease. The radiological features are distinct from other conditions demonstrating recognisable patterns of ICC, such as congenital cytomegalovirus infection and Aicardi-Goutires syndrome. In the absence of a known risk factor for periventricular leukomalacia, the presence of these radiological findings should suggest the possibility of COL4A1-related disease. © Georg Thieme Verlag KG Stuttgart - New York.

Parr J.R.,Royal Infirmary | Jolleff N.,Neuroscience Unit | Gray L.,Royal Infirmary | Gibbs J.,Countess of Chester Hospital NHS Foundation Trust | And 2 more authors.
Child: Care, Health and Development | Year: 2013

Objectives: To identify how services provided by child development teams (CDTs) have changed over 20 years. To what extent have major government initiatives aiming to improve the lives of children with disability and their families been implemented by teams? Design: Survey sent to every UK CDT in 2009/2010; comparison with data gathered in 1988 and 1999. Results: Ninety-four per cent (225/240) of CDTs responded; data on 242 teams were available from 1999 and 125 teams from 1988. Despite policy recommendations advocating the value of interdisciplinary team working, there was a decline in numbers of professionals working within the CDT multidisciplinary team. One-third of all teams reported a reduction in their funding over the last 5 years. However, specialist clinics provided increased. Teams reported patchy adoption of national initiatives designed to improve provision. Transition services were underdeveloped. Conclusions: This comprehensive survey of UK CDT service provision, as well as national studies of the healthcare experience of families with a disabled child, shows that improvements in provision are required. © 2013 John Wiley & Sons Ltd.

Olopade J.O.,Neuroscience Unit | Fatola I.O.,University of Ibadan | Olopade F.E.,University of Ibadan
Nigerian Journal of Physiological Sciences | Year: 2011

The work investigated the protective role of vitamin E on vanadium induced neurotoxicity. Three adult female rats were divided into three groups, A-C with each dam and her pups forming a group. Group A served as control. The dam in Group B was given 3mg/kg b.w./day of vanadium from PND 1 while the Group C dam were given 3mg/kg b.w./day of vanadium, for 14 days and 500mg/kg b.w. of vitamin E 72 hourly in the same time frame. The results showed that pups from Group B, exhibited behavioural deficits in most tests, a significant reduction in body weight gain and absolute brain weight; in addition immunohistochemistry showed reactive astrogliosis induced by vanadium exposure. All these findings were however attenuated in pups whose dam was exposed to vanadium and vitamin E depicting the significant protective effects of this antioxidant against vanadium. This study is novel in that both vanadium and vitamin E were introduced through the lactation route. We conclude that though caution remains essential in the posology of vitamin E, the management of lactating mothers who have been exposed to vanadium occupationally, environmentally or therapeutically with supplementation of this antioxidant may be beneficial at least in the short term to both mother and offspring. © Physiological Society of Nigeria.

Koutras C.,Laval University | Koutras C.,Neuroscience Unit | Koutras C.,University of Toronto | Levesque G.,Laval University | Levesque G.,Neuroscience Unit
PLoS ONE | Year: 2011

Neural plakophilin-related armadillo protein (NPRAP or δ-catenin) is a neuronal-specific protein that is best known for its interaction with presenilin 1 (PS1). Interestingly, the hemizygous loss of NPRAP is associated with severe mental retardation in cri du chat syndrome (CDCS), and mutations in PS1 cause an aggressive, early-onset form of Alzheimer's disease. Until recently, studies on the function of NPRAP have focused on its ability to modulate dendritic protrusion elaboration through its binding to cell adhesion and scaffolding molecules. However, mounting evidence indicates that NPRAP participates in intracellular signaling and exists in the nucleus, where it modulates gene expression. This apparent bifunctional nature suggests an elaborate neuronal role, but how NPRAP came to participate in such distinct subcellular events remains a mystery. To gain insight into this pathway, we immunoprecipitated NPRAP from human SH SY5Y cells and identified several novel interacting proteins by mass spectrometry. These included neurofilament alpha-internexin, interferon regulatory protein 2 binding factors, and dynamins 1 and 2. We further validated dynamin 2/NPRAP colocalization and direct interaction in vivo, confirming their bona fide partnership. Interestingly, dynamin 2 has established roles in endocytosis and actin assembly, and both of these processes have the potential to interface with the cell adhesion and intracellular signaling processes that involve NPRAP. Our data provide new avenues for approaching NPRAP biology and suggest a broader role for this protein than previously thought. © 2011 Koutras, Lévesque.

Sim T.,Hong Kong Polytechnic University | Gentile D.A.,Iowa State University | Bricolo F.,Neuroscience Unit | Serpelloni G.,Neuroscience Unit | Gulamoydeen F.,Singapore National Institute of Education
International Journal of Mental Health and Addiction | Year: 2012

Preliminary research studies suggest that some people who use computer, video games, and the Internet heavily develop dysfunctional symptoms, often referred to in the popular press as an "addiction." Although several studies have measured various facets of this issue, there has been no common framework within which to view these studies. This paper aims to provide a conceptual framework of "impulse control disorders" and describe what is known currently based on a review of the international literature, and highlight what remains to be studied. We suggest the term "Pathological Technology Use" (PTU) rather than "internet addiction", since there is robust construct validity (via convergent validity and comorbidity) for pathological computer, video game and Internet use, regardless of how individual researchers defined or measured it. Questions concerning diagnostic criteria are raised, and a common set of diagnostic criteria is proposed. © 2012 Springer Science+Business Media, LLC.

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