Publications
160 results found
Srai SK, Kallo V, Ward R, et al., 2016, THE EFFECT OF NEUROINFLAMMATION ON IRON REGULATION IN CELLS OF THE CENTRAL NERVOUS SYSTEM, AMERICAN JOURNAL OF HEMATOLOGY, Vol: 91, Pages: E165-E165, ISSN: 0361-8609
Bastida A, Ward R, Piccini P, et al., 2016, SYSTEMIC INFLAMMATION INFLUENCES THE ABILITY OF DEFERIPRONE TO CHELATE IRON FROM SPECIFIC BRAIN REGIONS IN PARKINSON'S DISEASE PATIENTS, AMERICAN JOURNAL OF HEMATOLOGY, Vol: 91, Pages: E232-E232, ISSN: 0361-8609
Harrison IF, Anis HK, Dexter DT, 2016, Associated degeneration of ventral tegmental area dopaminergic neurons in the rat nigrostriatal lactacystin model of parkinsonism and their neuroprotection by valproate., Neuroscience Letters, Vol: 614, Pages: 16-23, ISSN: 1872-7972
Parkinson's disease (PD) manifests clinically as bradykinesia, rigidity, and development of a resting tremor, primarily due to degeneration of dopaminergic nigrostriatal pathways in the brain. Intranigral administration of the irreversible ubiquitin proteasome system inhibitor, lactacystin, has been used extensively to model nigrostriatal degeneration in rats, and study the effects of candidate neuroprotective agents on the integrity of the dopaminergic nigrostriatal system. Recently however, adjacent extra-nigral brain regions such as the ventral tegmental area (VTA) have been noted to also become affected in this model, yet their integrity in studies of candidate neuroprotective agents in the model have largely been overlooked. Here we quantify the extent and distribution of dopaminergic degeneration in the VTA of rats intranigrally lesioned with lactacystin, and quantify the extent of VTA dopaminergic neuroprotection after systemic treatment with an epigenetic therapeutic agent, valproate, shown previously to protect dopaminergic SNpc neurons in this model. We found that unilateral intranigral administration of lactacystin resulted in a 53.81% and 31.72% interhemispheric loss of dopaminergic SNpc and VTA neurons, respectively. Daily systemic treatment of lactacystin lesioned rats with valproate however resulted in dose-dependant neuroprotection of VTA neurons. Our findings demonstrate that not only is the VTA also affected in the intranigral lactacystin rat model of PD, but that this extra-nigral brain region is substrate for neuroprotection by valproate, an agent shown previously to induce neuroprotection and neurorestoration of SNpc dopaminergic neurons in this model. Our results therefore suggest that valproate is a candidate for extra-nigral as well as intra-nigral neuroprotection.
Ruffmann C, Calboli FC, Bravi I, et al., 2015, Cortical Lewy bodies and Aβ burden are associated with prevalence and timing of dementia in Lewy body diseases., Neuropathology and Applied Neurobiology, Vol: 42, Pages: 436-450, ISSN: 1365-2990
AIMS: Our main objective was to determine the neuropathological correlates of dementia in patients with Lewy body disease (LBD). Furthermore, we used data derived from clinical, neuropathological and genetic studies to investigate boundary issues between Dementia with Lewy bodies (DLB) and Parkinson's disease with (PDD) and without (PDND) dementia. METHODS: 121 cases with a neuropathological diagnosis of LBD and clinical information on dementia status were included in the analysis (55 PDD, 17 DLB and 49 PDND). We carried out topographical and semi-quantitative assessment of Lewy bodies (LB), Aβ plaques and tau-positive neuropil threads (NT). The APOE genotype and MAPT haplotype status were also determined. RESULTS: The cortical LB (CLB) burden was the only independent predictor of dementia (OR: 4.12, p<0.001). The total cortical Aβ plaque burden was an independent predictor of a shorter latency to dementia from onset of motor signs (p=0.001). DLB cases had a higher LB burden in the parietal and temporal cortex, compared to PDD. Carrying at least one APOE ϵ4 allele was associated with a higher cortical LB burden (p=0.02), particularly in the neocortical frontal, parietal, and temporal regions. CONCLUSIONS: High CLB burden is a key neuropathological substrate of dementia in LBD. Elevated cortical LB pathology and Aβ plaque deposition are both correlated with a faster progression to dementia. The higher CLB load in the temporal and parietal regions, which seems to be a distinguishing feature of DLB, may account for the shorter latency to dementia and could be mediated by the APOE ϵ4 allele. This article is protected by copyright. All rights reserved.
Ilse S Pienaar, Sarah E Gartside, Puneet Sharma, et al., 2015, Pharmacogenetic stimulation of cholinergic pedunculopontine neurons reverses motor deficits in a rat model of Parkinson’s disease, Molecular Neurodegeneration, Vol: 10, ISSN: 1750-1326
Background: Patients with advanced Parkinson's disease (PD) often present with axial symptoms, includingpostural- and gait difficulties that respond poorly to dopaminergic agents. Although deep brain stimulation (DBS) ofa highly heterogeneous brain structure, the pedunculopontine nucleus (PPN), improves such symptoms, theunderlying neuronal substrate responsible for the clinical benefits remains largely unknown, thus hamperingoptimization of DBS interventions. Choline acetyltransferase (ChAT)::Cre+ transgenic rats were sham-lesioned orrendered parkinsonian through intranigral, unihemispheric stereotaxic administration of the ubiquitin-proteasomalsystem inhibitor, lactacystin, combined with designer receptors exclusively activated by designer drugs (DREADD),to activate the cholinergic neurons of the nucleus tegmenti pedunculopontine (PPTg), the rat equivalent of thehuman PPN. We have previously shown that the lactacystin rat model accurately reflects aspects of PD, including apartial loss of PPTg cholinergic neurons, similar to what is seen in the post-mortem brains of advanced PD patients.Results: In this manuscript, we show that transient activation of the remaining PPTg cholinergic neurons in thelactacystin rat model of PD, via peripheral administration of the cognate DREADD ligand, clozapine-N-oxide (CNO),dramatically improved motor symptoms, as was assessed by behavioral tests that measured postural instability, gait,sensorimotor integration, forelimb akinesia and general motor activity. In vivo electrophysiological recordingsrevealed increased spiking activity of PPTg putative cholinergic neurons during CNO-induced activation. c-Fosexpression in DREADD overexpressed ChAT-immunopositive (ChAT+) neurons of the PPTg was also increased byCNO administration, consistent with upregulated neuronal activation in this defined neuronal population.Conclusions: Overall, these findings provide evidence that functional modulation of PPN cholinergic neuronsalleviates parkinson
Goode AE, Gonzalez Carter DA, Motskin M, et al., 2015, High resolution and dynamic imaging of biopersistence and bioreactivity of extra and intracellular MWNTs exposed to microglial cells, Biomaterials, Vol: 70, Pages: 57-70, ISSN: 1878-5905
Multi-walled carbon nanotubes (MWNTs) are increasingly being developed both as neuro-therapeutic drug delivery systems to the brain and as neural scaffolds to drive tissue regeneration across lesion sites. MWNTs with different degrees of acid oxidation may have different bioreactivities and propensities to aggregate in the extracellular environment, and both individualised and aggregated MWNTs may be expected to be found in the brain. Before practical application, it is vital to understand how both aggregates and individual MWNTs will interact with local phagocytic immune cells, the microglia, and ultimately to determine their biopersistence in the brain. The processing of extra- and intracellular MWNTs (both pristine and when acid oxidised) by microglia was characterised across multiple length scales by correlating a range of dynamic, quantitative and multi-scale techniques, including: UV-vis spectroscopy, light microscopy, focussed ion beam scanning electron microscopy and transmission electron microscopy. Dynamic, live cell imaging revealed the ability of microglia to break apart and internalise micron-sized extracellular agglomerates of acid oxidised MWNT, but not pristine MWNTs. The total amount of MWNTs internalised by, or strongly bound to, microglia was quantified as a function of time. Neither the significant uptake of oxidised MWNTs, nor the incomplete uptake of pristine MWNTs affected microglial viability, pro-inflammatory cytokine release or nitric oxide production. However, after 24 hrs exposure to pristine MWNTs, a significant increase in the production of reactive oxygen species was observed. Small aggregates and individualised oxidised MWNTs were present in the cytoplasm and vesicles, including within multilaminar bodies, after 72 hours. Some evidence of morphological damage to oxidised MWNT structure was observed including highly disordered graphitic structures, suggesting possible biodegradation. This work demonstrates the utility of dynamic, quant
Harrison IF, Crum WR, Vernon AC, et al., 2015, Neurorestoration induced by the HDAC inhibitor sodium valproate in the lactacystin model of Parkinson's is associated with histone acetylation and up-regulation of neurotrophic factors, British Journal of Pharmacology, Vol: 172, Pages: 4200-4215, ISSN: 1476-5381
Background and PurposeHistone hypoacetylation is associated with Parkinson's disease (PD), due possibly to an imbalance in the activities of enzymes responsible for histone (de)acetylation; correction of which may be neuroprotective/neurorestorative. This hypothesis was tested using the anti-epileptic drug sodium valproate, a known histone deacetylase inhibitor (HDACI), utilizing a delayed-start study design in the lactacystin rat model of PD.Experimental ApproachThe irreversible proteasome inhibitor lactacystin was unilaterally injected into the substantia nigra of Sprague–Dawley rats that subsequently received valproate for 28 days starting 7 days after lactacystin lesioning. Longitudinal motor behavioural testing, structural MRI and post-mortem assessment of nigrostriatal integrity were used to track changes in this model of PD and quantify neuroprotection/restoration. Subsequent cellular and molecular analyses were performed to elucidate the mechanisms underlying valproate's effects.Key ResultsDespite producing a distinct pattern of structural re-modelling in the healthy and lactacystin-lesioned brain, delayed-start valproate administration induced dose-dependent neuroprotection/restoration against lactacystin neurotoxicity, characterized by motor deficit alleviation, attenuation of morphological brain changes and restoration of dopaminergic neurons in the substantia nigra. Molecular analyses revealed that valproate alleviated lactacystin-induced histone hypoacetylation and induced up-regulation of brain neurotrophic/neuroprotective factors.Conclusions and ImplicationsThe histone acetylation and up-regulation of neurotrophic/neuroprotective factors associated with valproate treatment culminate in a neuroprotective and neurorestorative phenotype in this animal model of PD. As valproate induced structural re-modelling of the brain, further research is required to determine whether valproate represents a viable candidate for disease treatment; however, the re
Brauer R, Bhaskaran K, Chaturvedi N, et al., 2015, Glitazone Treatment and Incidence of Parkinson's Disease among People with Diabetes: A Retrospective Cohort Study, PLOS Medicine, Vol: 12, ISSN: 1549-1277
BackgroundRecent in vitro and animal experiments suggest that peroxisome proliferation-activatedreceptor gamma (PPARɣ) agonist medications, such as antidiabetic glitazone (GTZ) drugs,are neuroprotective in models of Parkinson’s disease (PD). These findings have not beentested in humans. We hypothesized that individuals prescribed GTZ drugs would have alower incidence of PD compared to individuals prescribed other treatments for diabetes.Methods and FindingsUsing primary care data from the United Kingdom Clinical Practice Research Datalink(CPRD), we conducted a retrospective cohort study in which individuals with diabetes whowere newly prescribed GTZ (GTZ-exposed group) were matched by age, sex, practice,and diabetes treatment stage with up to five individuals prescribed other diabetes treatments(other antidiabetic drug-exposed group). Patients were followed up from 1999 untilthe first recording of a PD diagnosis, end of observation in the database, or end of the study(1 August 2013). An incidence rate ratio (IRR) was calculated using conditional Poissonregression, adjusted for possible confounders. 44,597 GTZ exposed individuals werematched to 120,373 other antidiabetic users. 175 GTZ-exposed individuals were diagnosedwith PD compared to 517 individuals in the other antidiabetic drug-exposed group. The incidencerate (IR) of PD in the GTZ-exposed group was 6.4 per 10,000 patient years comparedwith 8.8 per 10,000 patient years in those prescribed other antidiabetic treatments(IRR 0.72, 95% confidence interval [CI] 0.60–0.87). Adjustments for potential confoundingvariables, including smoking, other medications, head injury, and disease severity, had nomaterial impact (fully adjusted IRR 0.75, 0.59–0.94). The risk was reduced in those with currentGTZ prescriptions (current GTZ-exposed IRR 0.59, 0.46–0.77) but not reduced amongthose with past prescriptions (past GTZ-exposed IRR 0.85, 0.65–1.10). Our study only included patients with diabetes
Klioueva NM, Rademaker MC, Dexter DT, et al., 2015, BrainNet Europe's Code of Conduct for brain banking, Journal of Neural Transmission, Vol: 122, Pages: 937-940, ISSN: 1435-1463
Research utilizing human tissue and its removalat post-mortem has given rise to many controversies in themedia and posed many dilemmas in the fields of law andethics. The law often lacks clear instructions and unambiguousguidelines. The absence of a harmonized internationallegislation with regard to post-mortem medicalprocedures and donation of tissue and organs contributes tothe complexity of the issue. Therefore, within the BrainNetEurope (BNE) consortium, a consortium of 19 Europeanbrain banks, we drafted an ethical Code of Conduct forbrain banking that covers basic legal rules and bioethicalprinciples involved in brain banking. Sources include laws,regulations and guidelines (Declarations, Conventions,Recommendations, Guidelines and Directives) issued byinternational key organizations, such as the Council ofEurope, European Commission, World Medical Associationand World Health Organization. The Code of Conductaddresses fundamental topics as the rights of the personsdonating their tissue, the obligations of the brain bank withregard to respect and observance of such rights, informedconsent, confidentiality, protection of personal data, collectionsof human biological material and their management,and transparency and accountability within theorganization of a brain bank. The Code of Conduct forbrain banking is being adopted by the BNE network priorto being enshrined in official legislation for brain bankingin Europe and beyond.
Durrenberger PF, Fernando FS, Kashefi SN, et al., 2015, Common mechanisms in neurodegeneration and neuroinflammation: a BrainNet Europe gene expression microarray study, JOURNAL OF NEURAL TRANSMISSION, Vol: 122, Pages: 1055-1068, ISSN: 0300-9564
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- Citations: 88
Ward RJ, Dexter DT, Crichton RR, 2015, Ageing, neuroinflammation and neurodegeneration., Front Biosci (Schol Ed), Vol: 7, Pages: 189-204
During ageing, different iron complexes accumulate in specific brain regions which are associated with motor and cognitive dysfunction. In neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, changes in local iron homoeostasis result in altered cellular iron distribution and accumulation, ultimately inducing neurotoxicity. The use of iron chelators which are able to penetrate the blood brain barrier and reduce excessive iron accumulation in specific brain regions have been shown to reduce disease progression in both Parkinson's disease and Friedreich's Ataxia. Neuroinflammation often occurs in neurodegenerative diseases, which is mainly sustained by activated microglia exhibiting the M1 phenotype. Such inflammation contributes to the disease progression. Therapeutic agents which reduce such inflammation, e.g. taurine compounds, may ameliorate the inflammatory process by switching the microglia from a M1 to a M2 phenotype.
Ward RJ, Dexter DT, Crichton RR, 2015, Ageing, neuroinflammation and neurodegeneration, Frontiers in Bioscience - Scholar, Vol: 7, Pages: 189-204, ISSN: 1945-0524
During ageing, different iron complexes accumulate in specific brain regions which are associated with motor and cognitive dysfunction. In neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, changes in local iron homoeostasis result in altered cellular iron distribution and accumulation, ultimately inducing neurotoxicity. The use of iron chelators which are able to penetrate the blood brain barrier and reduce excessive iron accumulation in specific brain regions have been shown to reduce disease progression in both Parkinson's disease and Friedreich's Ataxia. Neuroinflammation often occurs in neurodegenerative diseases, which is mainly sustained by activated microglia exhibiting the M1 phenotype. Such inflammation contributes to the disease progression. Therapeutic agents which reduce such inflammation, e.g. taurine compounds, may ameliorate the inflammatory process by switching the microglia from a M1 to a M2 phenotype.
Hurley MJ, Durrenberger PF, Gentleman SM, et al., 2015, Altered Expression of Brain Proteinase-Activated Receptor-2, Trypsin-2 and Serpin Proteinase Inhibitors in Parkinson's Disease, Journal of Molecular Neuroscience, Vol: 57, Pages: 48-62, ISSN: 1559-1166
Neuroinflammation is thought to contribute to celldeath in neurodegenerative disorders, but the factors involvedin the inflammatory process are not completely understood.Proteinase-activated receptor-2 (PAR2) expression in brain isincreased in Alzheimer’s disease and multiple sclerosis, butthe status of PAR2 in Parkinson’s disease is unknown. Thisstudy examined expression of PAR2 and endogenous proteinaseactivators (trypsin-2, mast cell tryptase) and proteinaseinhibitors (serpin-A5, serpin-A13) in areas vulnerable and resistantto neurodegeneration in Parkinson’s disease at differentBraak α-synuclein stages of the disease in post-mortem brain.In normal aged brain, expression of PAR-2, trypsin-2, andserpin-A5 and serpin-A13 was found in neurons and microglia,and alterations in the amount of immunoreactivity for theseproteins were found in some brain regions. Namely, therewas a decrease in neurons positive for serpin-A5 in the dorsalmotor nucleus, and serpin-A13 expression was reduced in thelocus coeruleus and primary motor cortex, while expression ofPAR2, trypsin-2 and both serpins was reduced in neuronswithin the substantia nigra. There was an increased numberof microglia that expressed serpin-A5 in the dorsal motor nucleusof vagus and elevated numbers of microglia thatexpressed serpin-A13 in the substantia nigra of lateParkinson’s disease cases. The number of microglia thatexpressed trypsin-2 increased in primary motor cortex of incidentalLewy body disease cases. Analysis of Parkinson’sdisease cases alone indicated that serpin-A5 and serpin-A13,and trypsin-2 expression in midbrain and cerebral cortex wasdifferent in cases with a high incidence of L-DOPA-induceddyskinesia and psychosis compared to those with low levels ofthese treatment-induced side effects. This study showed thatthere was altered expression in brain of PAR2 and some proteinsthat can control its function in Parkinson’s disease. Giventhe role of PAR2 in neuroi
Cornelis MC, Byrne EM, Esko T, et al., 2015, Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption, MOLECULAR PSYCHIATRY, Vol: 20, Pages: 647-656, ISSN: 1359-4184
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- Citations: 178
Hurley MJ, Gentleman SM, Dexter DT, 2015, Calcium CaV1 Channel Subtype mRNA Expression in Parkinson's Disease Examined by In Situ Hybridization, Journal of Molecular Neuroscience, Vol: 55, Pages: 715-724, ISSN: 0895-8696
The factors which make some neurons vulnerable to neurodegeneration in Parkinson's disease while others remain resistant are not fully understood. Studies in animal models of Parkinson's disease suggest that preferential use of CaV1.3 subtypes by neurons may contribute to the neurodegenerative process by increasing mitochondrial oxidant stress. This study quantified the level of mRNA for the CaV1 subtypes found in the brain by in situ hybridization using CaV1 subtype-specific [35S]-radiolabelled oligonucleotide probes. In normal brain, the greatest amount of messenger RNA (mRNA) for each CaV1 subtype was found in the midbrain (substantia nigra), with a moderate level in the pons (locus coeruleus) and lower quantities in cerebral cortex (cingulate and primary motor). In Parkinson's disease, the level of CaV1 subtype mRNA was maintained in the midbrain and pons, despite cell loss in these areas. In cingulate cortex, CaV1.2 and CaV1.3 mRNA increased in cases with late-stage Parkinson's disease. In primary motor cortex, the level of CaV1.2 mRNA increased in late-stage Parkinson's disease. The level of CaV1.3 mRNA increased in primary motor cortex of cases with early-stage Parkinson's disease and normalized to near the control level in cases from late-stage Parkinson's disease. The finding of elevated CaV1 subtype expression in cortical brain regions supports the view that disturbed calcium homeostasis is a feature of Parkinson's disease throughout brain and not only a compensatory consequence to the neurodegenerative process in areas of cell loss. © 2014 Springer Science+Business Media New York.
Pienaar IS, Lee CH, Elson JL, et al., 2015, Deep-brain stimulation associates with improved microvascular integrity in the subthalamic nucleus in Parkinson's disease, NEUROBIOLOGY OF DISEASE, Vol: 74, Pages: 392-405, ISSN: 0969-9961
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- Citations: 68
Ward RJ, Dexter DT, Crichton RR, 2015, Neurodegenerative diseases and therapeutic strategies using iron chelators, Journal of Trace Elements in Medicine and Biology, Vol: 31, Pages: 267-273, ISSN: 0946-672X
This review will summarise the current state of our knowledge concerning the involvement of iron in various neurological diseases and the potential of therapy with iron chelators to retard the progression of the disease. We first discuss briefly the role of metal ions in brain function before outlining the way by which transition metal ions, such as iron and copper, can initiate neurodegeneration through the generation of reactive oxygen and nitrogen species. This results in protein misfolding, amyloid production and formation of insoluble protein aggregates which are contained within inclusion bodies. This will activate microglia leading to neuroinflammation. Neuroinflammation plays an important role in the progression of the neurodegenerative diseases, with activated microglia releasing pro-inflammatory cytokines leading to cellular cell loss. The evidence for metal involvement in Parkinson's and Alzheimer's disease as well as Friedreich's ataxia and multiple sclerosis will be presented. Preliminary results from trials of iron chelation therapy in these neurodegenerative diseases will be reviewed.
Di Fruscia P, Zacharioudakis E, Liu C, et al., 2015, The Discovery of a Highly Selective 5,6,7,8-Tetrahydrobenzo[4,5]thieno[ 2,3-<i>d</i>] pyrimidin-4(3<i>H</i>)-one SIRT2 Inhibitor that is Neuroprotective in an in vitro Parkinson's Disease Model, CHEMMEDCHEM, Vol: 10, Pages: 69-82, ISSN: 1860-7179
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- Citations: 58
Pienaar IS, Dexter DT, Gradinaru V, 2015, Neurophysiological and Optogenetic Assessment of Brain Networks Involved in Motor Control, MOVEMENT DISORDERS: GENETICS AND MODELS, 2ND EDITION, Editors: LeDoux, Publisher: ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD, Pages: 187-199, ISBN: 978-0-12-405195-9
Reynolds R, Howell OW, Magliozzi R, et al., 2014, In the search for molecular hallmarks of neuroinflammation in brain diseases, 12th International Congress of Neuroimmunology (ISNI), Publisher: ELSEVIER SCIENCE BV, Pages: 147-147, ISSN: 0165-5728
Brauer R, Bhaskaran K, Chaturvedi N, et al., 2014, Glitazone Antidiabetics and the Risk of Parkinson's Disease, PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Vol: 23, Pages: 336-336, ISSN: 1053-8569
Nalls MA, Pankratz N, Lill CM, et al., 2014, Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease, Nature Genetics, Vol: 46, Pages: 989-993, ISSN: 1546-1718
We conducted a meta-analysis of Parkinson's disease genome-wide association studies using a common set of 7,893,274 variants across 13,708 cases and 95,282 controls. Twenty-six loci were identified as having genome-wide significant association; these and 6 additional previously reported loci were then tested in an independent set of 5,353 cases and 5,551 controls. Of the 32 tested SNPs, 24 replicated, including 6 newly identified loci. Conditional analyses within loci showed that four loci, including GBA, GAK-DGKQ, SNCA and the HLA region, contain a secondary independent risk variant. In total, we identified and replicated 28 independent risk variants for Parkinson's disease across 24 loci. Although the effect of each individual locus was small, risk profile analysis showed substantial cumulative risk in a comparison of the highest and lowest quintiles of genetic risk (odds ratio (OR) = 3.31, 95% confidence interval (CI) = 2.55–4.30; P = 2 × 10−16). We also show six risk loci associated with proximal gene expression or DNA methylation.
Ward RJ, Lallemand F, Dexter DT, et al., 2014, Sy39-4influence of systemic inflammatory processes on brain immune system., Alcohol Alcohol, Vol: 49 Suppl 1
Alcohol-induced inflammation plays an important part in the induction of alcohol induced brain damage. Increased peripheral inflammation, with the production of pro-inflammatory cytokines, possibly as a result of bacterial interaction with alcohol, acetaldehyde toxicity, macrophage stimulation or other factors, may act as important chemical messengers, which are able to traverse the blood brain barrier, BBB, and affect central nervous system function. Indeed in adolescent binge drinkers, changes in the plasma ratios of pro-inflammatory to anti-inflammatory cytokines are eviden. Once these cytokines have crossed the BBB, they may interact with receptors on glial cells thus enhancing the production of pro-inflammatory mediators which may lead to cognitive dysfunction. Since glial cells play an important role in the removal of neurotransmitter at the synaptic cleft, their activation may adversely affect this process thereby further contributing to cognitive dysfunction and depression. In addition increased glutamate excitotoxicity, as a result of alcohol detoxification, may contribute to the pro-inflammatory milieu. Animal studies have shown that the suppression of such an inflammatory response in the brain induced by chronic alcohol abuse and binge drinking by the administration of taurine analogues is beneficial in reducing both the inflammation and excessive glutamate production.
Ward RJ, Lallemand E, Dexter DT, et al., 2014, INFLUENCE OF SYSTEMIC INFLAMMATORY PROCESSES ON BRAIN IMMUNE SYSTEM, ALCOHOL AND ALCOHOLISM, Vol: 49, ISSN: 0735-0414
Goode AE, Hine NDM, Chen S, et al., 2014, Electron microscopic characterization of functionalized multi-walled carbon nanotubes and their interactions with the blood brain barrier, Pages: 1744-1745, ISSN: 1431-9276
Pienaar I, Sharma P, Elson JL, et al., 2014, A DREADD approach for acute stimulation of cholinergic neurons of the pedunculopontine nucleus reverses Parkinsonism in the lactacystin model of Parkinson's disease (2014), Movement Disorders, Vol: 2014;29 Suppl 1 :381, ISSN: 1531-8257
Dong J, Gao J, Nalls M, et al., 2014, Susceptibility loci for pigmentation and melanoma in relation to Parkinson's disease, Neurobiology of Aging, Vol: 35, Pages: 1512.e5-1512.e10, ISSN: 0197-4580
Dexter DT, Gveric D, Gentleman S, et al., 2014, Parkinson's UK Tissue Bank: A unique tissue resource for fostering Parkinson's disease research, 18th International Congress of Parkinson's Disease and Movement Disorders, Publisher: WILEY-BLACKWELL, Pages: S8-S9, ISSN: 0885-3185
Dexter DT, Martin-Bastida A, Kabba C, et al., 2014, A pilot 6 months efficacy and safety study utilising the iron chelator deferiprone in early stage Parkinson's disease, 18th International Congress of Parkinson's Disease and Movement Disorders, Publisher: WILEY-BLACKWELL, Pages: S234-S234, ISSN: 0885-3185
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Williams CJ, Dexter DT, 2014, Neuroprotective and symptomatic effects of targeting group III mGlu receptors in neurodegenerative disease, JOURNAL OF NEUROCHEMISTRY, Vol: 129, Pages: 4-20, ISSN: 0022-3042
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- Citations: 37
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