Book of abstracts - British Neuroscience Association
Book of abstracts - British Neuroscience Association
Book of abstracts - British Neuroscience Association
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53.04<br />
The role <strong>of</strong> the pedunculopontine nucleus in Parkinson’s disease<br />
Nandi D, Jenkinson E, Stein J F, Aziz T Z<br />
Oxford Functional Neurosurgery<br />
Gait freezing and poor balance are two <strong>of</strong> the most crippling and drug<br />
resistant symptoms <strong>of</strong> advanced Parkinson’s disease (PD) and also <strong>of</strong><br />
other untreatable disorders such as MSA and PSP. The<br />
pedunculopontine nucleus (PPN) has been implicated in these<br />
symptoms.<br />
The PPN is in the upper brain stem. The major inhibitory input is from<br />
the medial pallidum and SN reticulata and bilateral output is to the SN<br />
compacta, thalamus and spinal cord.<br />
Stimulation <strong>of</strong> the PPN in the decerebrate rat, cat and dog induced<br />
gait-like movements. In autopsy studies in PD, MSA, PSP and the<br />
DYT-1 dystonic brain, the PPN is degenerate. Autoradiography <strong>of</strong> the<br />
MPTP-parkinsonian primate shows excessive inhibition in the PPN.<br />
Lesions <strong>of</strong> the PPN in the normal primate induced PD-type<br />
bradykinesia which was persistent with bilateral lesions. In the MPTPprimate<br />
model, microinjections <strong>of</strong> the GABA antagonist bicuculine into<br />
the PPN reversed Parkinsonian akinesia implying that stimulation <strong>of</strong><br />
this region might have a therapeutic role in drug resistant PD [1]. Low<br />
frequency (5-10Hz) stimulation <strong>of</strong> the PPN in the same model<br />
reversed akinesia [2] independently <strong>of</strong> L-Dopa; moreover, L-Dopa and<br />
stimulation effects were additive [3,4], implying separate pathways.<br />
Clinical reports in PD patients by Mazzone [5] and other groups<br />
(Bristol, Toronto, Brisbane) showed that PPN stimulation did have the<br />
beneficial effects that were predicted by the primate studies.<br />
This research demonstrates the validity <strong>of</strong> the MPTP-primate model <strong>of</strong><br />
Parkinsonism and the role <strong>of</strong> the PPN in akinesia. Long term effects<br />
PPN stimulation need to be monitored.<br />
54.0<br />
Neurotrophins in development and diseases<br />
Barde Y-A<br />
Biozentrum, University <strong>of</strong> Basel Switzerland<br />
The neurotrophin gene family comprises 4 members with structural and<br />
functional similarities. While nerve growth factor was the founding member<br />
<strong>of</strong> the family, it is brain-derived neurotrophic factor (BDNF) that is<br />
expressed at the highest levels in all areas in the adult brain. These levels<br />
increase substantially post-natally and mouse models have been generated<br />
allowing the role <strong>of</strong> BDNF to be examined in the adult nervous system.<br />
Elaborate animal models <strong>of</strong> complete BDNF deprivation compatible with<br />
survival <strong>of</strong> adult animals are all the more desirable that in humans, gene<br />
polymorphisms and inactivation have been identified that significantly<br />
impact the behaviour <strong>of</strong> affected individuals.<br />
Most <strong>of</strong> the trophic actions <strong>of</strong> BDNF can be explained by its ability to<br />
activate the tyrosine kinase receptor TrkB. However, it has been clear for<br />
some time that the neurotrophin signalling system also comprises another<br />
pathway activated by the neurotrophin receptor p75. Its recruitment<br />
explains many <strong>of</strong> the “regressive” events associated with the neurotrophins<br />
and their receptors, including cell death in their most radical manifestation,<br />
as well as the limitation <strong>of</strong> axonal elongation and branching <strong>of</strong> dendrites. As<br />
the signalling events downstream <strong>of</strong> this receptor are still poorly<br />
understood, we recently begun to use neurons derived from embryonic<br />
stem cells to explore novel pathways activated by p75. We recently found<br />
that p75 transcriptionally increases the levels <strong>of</strong> an endogenous lectin<br />
which causes the degeneration <strong>of</strong> processes and that interfering with the<br />
activity <strong>of</strong> this lectin prevents the degeneration <strong>of</strong> neurons and <strong>of</strong> axons.<br />
55.0<br />
In vivo voltammetry: real-time monitoring <strong>of</strong> brain chemistry<br />
Lowry J P<br />
Sensors Development & Neurochemistry Research Units, BioAnalytics<br />
Laboratory, Department <strong>of</strong> Chemistry, National University <strong>of</strong> Ireland,<br />
Maynooth, Co. Kildare, Ireland.<br />
The importance <strong>of</strong> chemical signalling between cells in the functioning<br />
<strong>of</strong> neural networks is highlighted empirically by the use <strong>of</strong> drugs in the<br />
treatment <strong>of</strong> neurological disorders, such as Parkinson’s disease,<br />
schizophrenia and depression, as well as by mind-altering substances<br />
<strong>of</strong> abuse, all <strong>of</strong> which have specific chemical actions on brain neurons.<br />
A growing number <strong>of</strong> methodologies are being developed, including<br />
sampling (e.g. brain microdialysis), spectroscopic (e.g. fMRI) and<br />
electrochemical, to study neurochemical dynamics in the living brain.<br />
With the electrochemical approach, a microvoltammetric electrode is<br />
implanted in a specific brain region to monitor local changes in the<br />
concentration <strong>of</strong> substances in the extracellular fluid with sub-second<br />
time resolution over extended periods. This allows investigations <strong>of</strong><br />
the functions <strong>of</strong> specific chemicals in neuronal signalling, drug actions,<br />
and well defined behaviours.<br />
The development <strong>of</strong> new technologies for long-term in-vivo<br />
electrochemistry (LIVE) in the conscious brain is now possible<br />
following major advances in the fabrication <strong>of</strong> sensing devices using<br />
polymer-enzyme composites (PECs) synthesised in situ on the<br />
electrode surface. We have already demonstrated the feasibility <strong>of</strong><br />
using classical microelectrodes to monitor brain ascorbate, oxygen<br />
and blood flow, and PEC-based biosensors to monitor brain glucose in<br />
vivo. New in-vivo sensors for glutamate, hydrogen peroxide, NO and<br />
lactate, based on both classical and PEC designs are presently at<br />
various stages <strong>of</strong> development. In this presentation these LIVE<br />
devices will be described along with their application in novel studies<br />
<strong>of</strong> brain energy metabolism and animal models <strong>of</strong> psychiatric disease.<br />
56.01<br />
G2Cdb: The genes to cognition database.<br />
Croning M D R, Elliott P T, Marshall M C, McLaren P A, Grant S G N<br />
Genes to Cognition Programme, The Wellcome Trust Sanger Institute,<br />
Hinxton, Cambridge, CB10 1SA.<br />
<strong>Neuroscience</strong> databases linking genes, physiology, anatomy and<br />
behaviour across species will be valuable in a broad range <strong>of</strong> studies <strong>of</strong> the<br />
nervous system. G2Cdb is such a neuroscience database focused on<br />
synaptic proteins and diseases <strong>of</strong> the nervous system, specifically those<br />
affecting cognition, aiming to present a global view <strong>of</strong> the role <strong>of</strong> synapses<br />
in physiology and disease. It integrates human and mouse genomic<br />
information with available experimental resources including: synapse<br />
proteomics, human gene mutation information in CNS disease, brain gene<br />
expression resources, knockout mouse behavioural experiments, and<br />
electrophysiological studies <strong>of</strong> synaptic plasticity.<br />
It captures the experimental data output <strong>of</strong> the Wellcome Trust-funded<br />
Genes to Cognition Programme (G2C), our systematic curation <strong>of</strong> the<br />
relevant neuroscience literature, and data submitted directly to G2Cdb by<br />
investigators worldwide. Currently G2Cdb contains data on more than 1300<br />
genes, including: components <strong>of</strong> the NMDA receptor complex; postsynaptic<br />
density (PSD; Collins et al, 2006); knockout and transgenic mice (ca. 200<br />
lines) and complementary studies <strong>of</strong> human gene sequence variation<br />
(Grant et al, 2005).<br />
The databasL, Brandon, JM, Anderson, CN, Blackstock, WP, Choudhary<br />
JS and Grant SGN. J. Neurochem. (2006) 97 Suppl. 1:16-23.<br />
Grant, SG, Marshall, MC, Page KL, Cumiskey MA and Armstrong JD. Hum.<br />
Mol. Genet. (2005) 14 Spec. No. 2:R225-34.<br />
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