214 research outputs found
Neural Models of Normal and Abnormal Behavior: What Do Schizophrenia, Parkinsonism, Attention Deficit Disorder, and Depression Have in Common?
Defense Advanced Research Projects Agency and Office of Naval Research (N00014-95-1-0409); National Science Foundation (IRI-97-20333
Chronic NMDA administration to rats increases brain pro-apoptotic factors while decreasing anti-Apoptotic factors and causes cell death
<p>Abstract</p> <p>Background</p> <p>Chronic <it>N</it>-Methyl-d-aspartate (NMDA) administration to rats is reported to increase arachidonic acid signaling and upregulate neuroinflammatory markers in rat brain. These changes may damage brain cells. In this study, we determined if chronic NMDA administration (25 mg/kg i.p., 21 days) to rats would alter expression of pro- and anti-apoptotic factors in frontal cortex, compared with vehicle control.</p> <p>Results</p> <p>Using real time RT-PCR and Western blotting, chronic NMDA administration was shown to decrease mRNA and protein levels of anti-apoptotic markers Bcl-2 and BDNF, and of their transcription factor phospho-CREB in the cortex. Expression of pro-apoptotic Bax, Bad, and 14-3-3ζ was increased, as well as Fluoro-Jade B (FJB) staining, a marker of neuronal loss.</p> <p>Conclusion</p> <p>This alteration in the balance between pro- and anti-apoptotic factors by chronic NMDA receptor activation in this animal model may contribute to neuronal loss, and further suggests that the model can be used to examine multiple processes involved in excitotoxicity.</p
Predicting cognitive impairment in Parkinson's disease using neurophysiology and biochemical parameters as biomarkers
PhD ThesisParkinson’s disease (PD) is a common neurodegenerative condition with multiple
associated non-motor symptoms. Of these, dementia is a frequent debilitating
complication of the disorder, with significant morbidity and mortality. Some forms of
mild cognitive impairment in PD (PD-MCI) may represent a pre-dementia state and
certain clinical, laboratory and neurophysiological parameters may increase the
accuracy of prediction of cognitive decline. If validated, these markers would offer the
opportunity for disease modification and therapeutic intervention at a critical early
stage of the illness, when the viable neuronal population is greater. The key aim of this
thesis was to characterise cognitive impairment in PD in a cohort of newly diagnosed
cases, and evaluate how a panel of biomarkers correlated with cognitive phenotypes
to predict risk of future cognitive decline.
The main findings were that PD-MCI was common, and was associated with a distinct
clinical phenotype. Memory impairment was the most common single domain
affected, although the majority of those with PD-MCI were classified as nonamnestic
single domain subtype. A significant correlation was found between pattern
recognition memory, sensitive to temporal lobe impairments, and cerebrospinal
amyloid-β 1-42 levels, thought to represent amyloid-β metabolism and deposition
Both amyloid-β 1-42 and 1-40 levels were significantly lower in those with impaired
cognition. In addition, short latency afferent inhibition, a neurophysiological in vivo
non-invasive measurement of cholinergic function, was also reduced in participants
with mild cognitive impairment. These findings suggest that cholinergic dysfunction
and amyloid deposition may contribute to the underlying pathophysiology of early PD-
MCI.
The major conclusion from this thesis is that PD-MCI is heterogeneous and more
frequent than previously reported in early disease. This is associated with
abnormalities of amyloid processing and cholinergic dysfunction, and may highlight
those at risk of developing dementia. Longitudinal assessment of these individuals will
enable us to determine and better model those measures predictive of cognitive
decline at an early disease stage.Parkinson’s UK,
The Michael J Fox Foundation,
Newcastle University Lockhart Fun
Effects of domestication on biobehavioural profiles: a comparison of domestic guinea pigs and wild cavies from early to late adolescence
Zipser B, Schleking A, Kaiser S, Sachser N. Effects of domestication on biobehavioural profiles: a comparison of domestic guinea pigs and wild cavies from early to late adolescence. Frontiers in Zoology. 2014;11(1): 30
A neural network model of normal and abnormal learning and memory consolidation
The amygdala and hippocampus interact with thalamocortical systems to regulate cognitive-emotional learning, and lesions of amygdala, hippocampus, thalamus, and cortex have different effects depending on the phase of learning when they occur. In examining eyeblink conditioning data, several questions arise: Why is the hippocampus needed for trace conditioning where there is a temporal gap between the conditioned stimulus offset and the onset of the unconditioned stimulus, but not needed for delay conditioning where stimuli temporally overlap and co-terminate? Why do amygdala lesions made before or immediately after training decelerate conditioning while those made later have no impact on conditioned behavior? Why do thalamic lesions degrade trace conditioning more than delay conditioning? Why do hippocampal lesions degrade recent learning but not temporally remote learning? Why do cortical lesions degrade temporally remote learning, and cause amnesia, but not recent or post-lesion learning? How is temporally graded amnesia caused by ablation of medial prefrontal cortex? How are mechanisms of motivated attention and the emergent state of consciousness linked during conditioning? How do neurotrophins, notably Brain Derived Neurotrophic Factor (BDNF), influence memory formation and consolidation?
A neural model, called neurotrophic START, or nSTART, proposes answers to these questions. The nSTART model synthesizes and extends key principles, mechanisms, and properties of three previously published brain models of normal behavior. These three models describe aspects of how the brain can learn to categorize objects and events in the world; how the brain can learn the emotional meanings of such events, notably rewarding and punishing events, through cognitive-emotional interactions; and how the brain can learn to adaptively time attention paid to motivationally important events, and when to respond to these events, in a context-appropriate manner. The model clarifies how hippocampal adaptive timing mechanisms and BDNF may bridge the gap between stimuli during trace conditioning and thereby allow thalamocortical and corticocortical learning to take place and be consolidated. The simulated data arise as emergent properties of several brain regions interacting together. The model overcomes problems of alternative memory models, notably models wherein memories that are initially stored in hippocampus move to the neocortex during consolidation
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