Insult, injury and recovery in brain disease: From Molecules to therapeutic outcomes
Grant number: 236805
When nerve cells are damaged, destroyed or injured, through disease or trauma, common pathological processes are set in train. Even though there are many factors that might trigger disease, these inevitably lead to common processes that end in cell death or initiate protective processes. One theme involves the factors that surround these responses to nerve injury and stress, and the consequent protective and regenerative responses that ensue. Another theme, closely integrates with the first, is to exploit basic biological mechanisms with the aim of identifying and developing therapeutic targets for the management of a wider range of neurological conditions.
Related publications (33)
Bim Links ER Stress and Apoptosis in Cells Expressing Mutant SOD1 Associated with Amyotrophic Lateral Sclerosis
Kai Y Soo, Julie D Atkin, Manal Farg, Adam K Walker, Malcolm K Horne, Phillip Nagley
Endoplasmic reticulum (ER) stress is an important pathway to cell death in amyotrophic lateral sclerosis (ALS). We previously demo..
Modulation of Cellular Hsp72 Levels in Undifferentiated and Neuron-Like SH-SY5Y Cells Determines Resistance to Staurosporine-Induced Apoptosis
Lesley Cheng, Danielle J Smith, Robin L Anderson, Phillip Nagley
Increased expression of Hsp72 accompanies differentiation of human neuroblastoma SH-SY5Y cells to neuron-like cells. By modulating..
Protein disulphide isomerase protects against protein aggregation and is S-nitrosylated in amyotrophic lateral sclerosis
Adam K Walker, Manal A Farg, Chris R Bye, Catriona A McLean, Malcolm K Horne, Julie D Atkin
Amyotrophic lateral sclerosis is a rapidly progressing fatal neurodegenerative disease characterized by the presence of protein in..
GABAergic striatal neurons exhibit caspase-independent, mitochondrially mediated programmed cell death
Shanti Diwakarla, Linda D Mercer, Liubov Kardashsyan, Percy WY Chu, Yea Seul Shin, Chew L Lau, Maria LR Hughes, Phillip Nagley, Philip M Beart
GABAergic striatal neurons are compromised in basal ganglia pathologies and we analysed how insult nature determined their pattern..
A Differential Role for the Adenosine A(2A) Receptor in Opiate Reinforcement vs Opiate-Seeking Behavior
Robyn Mary Brown, Jennifer Lynn Short, Michael Scott Cowen, Catherine Ledent, Andrew John Lawrence
The adenosine A(2A) receptor is specifically enriched in the medium spiny neurons that make up the 'indirect' output pathway from ..
SK channel function regulates the dopamine phenotype of neurons in the substantia nigra pars compacta
TD Aumann, I Gantois, K Egan, A Vais, D Tomas, J Drago, MK Horne
Parkinson's disease (PD) is characterized by loss of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNc). I..
Endoplasmic reticulum stress and induction of the unfolded protein response in human sporadic amyotrophic lateral sclerosis
Julie D Atkin, Manal A Farg, Adam K Walker, Catriona McLean, Doris Tomas, Malcolm K Horne
The unfolded protein response (UPR) is induced at symptom onset and disease end stage in rodent models of familial amyotrophic lat..
Using behaviour to predict stroke severity in conscious rats: Post-stroke treatment with 3',4'-dihydroxyflavonol improves recovery
Carli L Roulston, Jennifer K Callaway, Bevyn Jarrott, Owen L Woodman, Gregory J Dusting
Prognostic models are used to predict outcome in stroke patients and to stratify treatment groups in clinical trials. No one has p..
Combined antagonism of glutamate mGlu5 and adenosine A(2A) receptors interact to regulate alcohol-seeking in rats
Cameron L Adams, Michael S Cowen, Jennifer L Short, Andrew J Lawrence
Adenosine and glutamate have been implicated as mediators involved in the self-administration of alcohol. In the present study we ..
Comparison of [H-3]-(2S,4R)-4-methylglutamate and [H-3]D-aspartate as ligands for binding and autoradiographic analyses of glutamate transporters
K Aprico, PM Beart, D Crawford, RD O'Shea
While studies with [(3)H]D-aspartate ([(3)H]d-Asp) illustrate specific interactions with excitatory amino acid transporters (EAATs..
Hierarchical recruitment by AMPA but not staurosporine of pro-apoptotic mitochondrial signaling in cultured cortical neurons: evidence for caspase-dependent/independent cross-talk
Philip M Beart, Maria LR Lim, Baohong Chen, Shanti Diwakarla, Linda D Mercer, Nam Sang Cheung, Phillip Nagley
Excitotoxicity mediated via the (S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) subtype of receptor for l-glutamat..
Ablation of D1 dopamine receptor-expressing cells generates mice with seizures, dystonia, hyperactivity, and impaired oral behavior
Ilse Gantois, Ke Fang, Luning Jiang, Daniela Babovic, Andrew J Lawrence, Vincenzo Ferreri, Yaroslav Teper, Bianca Jupp, Jenna Ziebell, Cristina M Morganti-Kossmann, Terence J O'Brien, Rachel Nally, Guenter Schuetz, John Waddington, Gary F Egan, John Drago
Huntington's disease is characterized by death of striatal projection neurons. We used a Cre/Lox transgenic approach to generate a..
Assessing appetitive and consummatory phases of ethanol self-administration in C57BL/6J mice under operant conditions: regulation by mGlu5 receptor antagonism
Michael S Cowen, Elena Krstew, Andrew J Lawrence
RATIONALE: The development of mouse models of ethanol consumption and ethanol-seeking behavior is of particular importance in unde..
Injury to axons and oligodendrocytes following endothelin-1-induced middle cerebral artery occlusion in conscious rats
Melissa M Gresle, Bevyn Jarrott, Nicole M Jones, Jennifer K Callaway
Injury to axons and oligodendrocytes has been poorly characterized in most animal models of stroke, and hence has been difficult t..
Hypoxic preconditioning produces differential expression of hypoxia-inducible factor-1 alpha (HIF-1 alpha) and its regulatory enzyme HIF prolyl hydroxylase 2 in neonatal rat brain
Nicole M Jones, Elizabeth M Lee, Timothy G Brown, Bevyn Jarrott, Philip M Beart
Hypoxic preconditioning can protect the brain against a subsequent damaging ischaemic insult. Mild hypoxia alone seems not suffici..
Chronic exposure to U18666A is associated with oxidative stress in cultured murine cortical neurons
Chor Hui Vivien Koh, Matthew Whiteman, Qiao-Xin Li, Barry Halliwell, Andrew M Jenner, Boon Seng Wong, Katrina M Laughton, Markus Wenk, Colin L Masters, Philip M Beart, Ora Bernard, Nam Sang Cheung
Findings that antioxidant treatment may be beneficial in Alzheimer's disease indicate that oxidative stress is an important factor..
The CRF1 receptor antagonist, antalarmin, reverses isolation-induced up-regulation of dopamine D-2 receptors in the amygdala and nucleus accumbens of Fawn-Hooded rats
Elvan Djouma, Katie Card, Daniel J Lodge, Andrew J Lawrence
We have previously shown that Fawn-Hooded (FH) rats reared in isolation display an anxiety-like phenotype and an enhanced acquisit..
Effects of lipopolysaccharide on glial phenotype and activity of glutamate transporters: Evidence for delayed up-regulation and redistribution of GLT-1
RD O'Shea, CL Lau, MC Farso, S Diwakarla, CJ Zagami, BB Svendsen, SJ Feeney, JK Callaway, NM Jones, DV Pow, NC Danbolt, B Jarrott, PM Beart
Excitatory amino acid transporters (EAATs) are responsible for homeostasis of extracellular L-glutamate, and the glial transporter..
Relative timing of redistribution of cytochrome c and Smac/DIABLO from mitochondria during apoptosis assessed by double immunocytochemistry on mammalian cells.
Maria LR Lim, Baohong Chen, Philip M Beart, Phillip Nagley
Redistribution of cytochrome c and Smac/DIABLO from mitochondria occurs during apoptosis, although the relative timing of their re..
The effects of estradiol on estrogen receptor and glutamate transporter expression in organotypic hippocampal cultures exposed to oxygen-glucose deprivation
Helena Cimarosti, Ross D O'Shea, Nicole M Jones, Ana Paula Horn, Fabricio Simao, Lauren L Zamin, Melissa Nassif, Rudimar Frozza, Carlos Alexandre Netto, Philip M Beart, Christianne Salbego
The molecular basis of estrogen-mediated neuroprotection against brain ischemia remains unclear. In the present study, we investig..
Differential effects of human neuromelanin and synthetic dopamine melanin on neuronal and glial cells
J Li, C Scheller, E Koutsilieri, F Griffiths, PM Beart, LD Mercer, G Halliday, E Kettle, D Rowe, P Riederer, M Gerlach, M Rodriguez, KL Double
We investigated the effects of neuromelanin (NM) isolated from the human substantia nigra and synthetic dopamine melanin (DAM) on ..
Hypoxic preconditioning in neonatal rat brain involves regulation of excitatory amino acid transporter 2 and estrogen receptor alpha
H Cimarosti, NM Jones, RD O'Shea, DV Pow, C Salbego, PM Beart
Exposure of the brain to a sublethal insult can protect against a subsequent brain injury. Hypoxic preconditioning induces toleran..
Chronic corticotropin-releasing factor type 1 receptor antagonism with antalarmin regulates the dopaminergic system of Fawn-Hooded rats
AJ Lawrence, CL Parish, F Chen, DJ Lodge, EV Krstew, K Card, DI Finkelstein, MK Horne
Corticotropin-releasing factor is a neuropeptide associated with the integration of physiological and behavioural responses to str..
Dietary polyphenols protect dopamine neurons from oxidative insults and apoptosis: investigations in primary rat mesencephalic cultures
LD Mercer, BL Kelly, MK Horne, PM Beart
Naturally occurring polyphenols have the potential to prevent oxidative damage in various pathophysiological conditions. Various m..
Sodium channel blocking activity of AM-36 and sipatrigine (BW619C89): in vitro and in vivo evidence
JK Callaway, M Castillo-Melendez, SF Giardina, EK Krstew, PM Beart, B Jarrott
Sodium channel blockers are neuroprotective against cerebral ischemia in animal models. A novel neuroprotective compound AM-36, wh..