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1.  Interactions between Stress and Vestibular Compensation – A Review 
Elevated levels of stress and anxiety often accompany vestibular dysfunction, while conversely complaints of dizziness and loss of balance are common in patients with panic and other anxiety disorders. The interactions between stress and vestibular function have been investigated both in animal models and in clinical studies. Evidence from animal studies indicates that vestibular symptoms are effective in activating the stress axis, and that the acute stress response is important in promoting compensatory synaptic and neuronal plasticity in the vestibular system and cerebellum. The role of stress in human vestibular disorders is complex, and definitive evidence is lacking. This article reviews the evidence from animal and clinical studies with a focus on the effects of stress on the central vestibular pathways and their role in the pathogenesis and management of human vestibular disorders.
PMCID: PMC3406321  PMID: 22866048
stress; vestibular compensation; plasticity
2.  Noisy Galvanic Vestibular Stimulation Promotes GABA Release in the Substantia Nigra and Improves Locomotion in Hemiparkinsonian Rats 
PLoS ONE  2012;7(1):e29308.
The vestibular system is connected to spinal, cerebellar and cerebral motor control structures and can be selectively activated with external electrodes. The resulting sensation of disturbed balance can be avoided by using stochastic stimulation patterns. Adding noise to the nervous system sometimes improves function. Small clinical trials suggest that stochastic vestibular stimulation (SVS) may improve symptoms in Parkinson's disease. We have investigated this claim and possible mechanisms using the 6-hydroxydopamine (6-OHDA) hemilesion model of Parkinson's disease.
Methodology/Principal Findings
Animals were tested in the accelerating rod test and the Montoya staircase test of skilled forelimb use. In 6-OHDA hemilesioned animals, SVS improved rod performance by 56±11 s. At group level L-DOPA treatment had no effect, but positive responders improved time on rod by 60±19 s. Skilled forelimb use was not altered by SVS. To investigate how SVS may influence basal ganglia network activity, intracerebral microdialysis was employed in four regions of interest during and after SVS. In presence of the γ-amino buturic acid (GABA) transporter inhibitor NNC 711, SVS induced an increase in GABA to 150±15% of baseline in the substantia nigra (SN) of unlesioned animals, but had no effect in the pedunculopontine nucleus (PPN), the striatum or the ventromedial thalamus (VM). Dopamine release remained stable in all areas, as did GABA and amine concentrations in the SN of unstimulated controls. Following SVS, a sustained increase in GABA concentrations was observed in the ipsilesional, but not in the contralesional SN of 6-OHDA hemilesioned rats. In contrast, L-DOPA treatment produced a similar increase of GABA in the ipsi- and contra-lesional SN.
SVS improves rod performance in a rat model of Parkinson's disease, possibly by increasing nigral GABA release in a dopamine independent way. We propose that SVS could be useful for treating symptoms of Parkinson's disease.
PMCID: PMC3253081  PMID: 22238601
3.  Loss of β-III spectrin leads to Purkinje cell dysfunction recapitulating the behaviour and neuropathology of SCA5 in humans 
Mutations in SPTBN2, the gene encoding β-III spectrin, cause spinocerebellar ataxia type 5 in humans (SCA5), a neurodegenerative disorder resulting in loss of motor coordination. How these mutations give rise to progressive ataxia and what the precise role β-III spectrin plays in normal cerebellar physiology are unknown. We developed a mouse lacking full length β-III spectrin and found that homozygous mice reproduced features of SCA5 including gait abnormalities, tremor, deteriorating motor coordination, Purkinje cell loss and cerebellar atrophy (molecular layer thinning). In vivo analysis reveals an age-related reduction in simple spike firing rate in surviving β-III−/− Purkinje cells while in vitro studies show these neurons to have reduced spontaneous firing, smaller sodium currents and dysregulation of glutamatergic neurotransmission. Our data suggest an early loss of EAAT4- (protein interactor of β-III spectrin) and subsequent loss of GLAST-mediated uptake may play a role in neuronal pathology. These findings implicate a loss of β-III spectrin function in SCA5 pathogenesis and indicate there are at least two physiological effects of β-III spectrin loss that underpin a progressive loss of inhibitory cerebellar output, namely an intrinsic Purkinje cell membrane defect due to reduced sodium currents and alterations in glutamate signaling.
PMCID: PMC2857506  PMID: 20371805
ataxia; cerebellum; motor coordination; glutamate transporters; excitotoxicity; neurodegeneration
4.  Advances in Auditory and Vestibular Medicine 
Audiological medicine  2009;7(4):180-188.
Auditory and Vestibular medicine is becoming more accepted as a specialty of its own, Medical NeurOtology. Recent advances in the field have been instrumental in the understanding of the scientific foundations, pathophysiology, clinical approach and management of patients with hearing and vestibular disorders. This paper will review these advances.
PMCID: PMC2920488  PMID: 20711412
Auditory and Vestibular Medicine; Ion homeostasis of the inner ear; vestibular compensation; vertigo; hearing loss; Meniere’s disease; vestibular migraine; BPPV; intratympanic perfusion; vestibular rehabilitation
5.  Differential proteomics analysis of synaptic proteins identifies potential cellular targets and protein mediators of synaptic neuroprotection conferred by the slow Wallerian degeneration (Wlds) gene 
Non-somatic synaptic and axonal compartments of neurons are primary pathological targets in many neurodegenerative conditions, ranging from Alzheimer's disease through to motor neuron disease. Axons and synapses are protected from degeneration by the slow Wallerian degeneration (Wlds) gene. Significantly, the molecular mechanisms through which this spontaneous genetic mutation delays degeneration remain controversial and the downstream protein targets of Wlds resident in non-somatic compartments remain unknown. Here we have used differential proteomic analysis to identify proteins whose expression levels were significantly altered in isolated synaptic preparations from the striatum of Wlds mice. 8 of the 16 proteins we identified as having modified expression levels in Wlds synapses are known regulators of mitochondrial stability and degeneration (including VDAC1, Aralar1 and mitofilin). Subsequent analyses demonstrated that other key mitochondrial proteins, not identified in our initial screen, are also modified in Wlds synapses. Of the non-mitochondrial proteins identified, several have been implicated in neurodegenerative diseases where synapses and axons are primary pathological targets (including DRP-2 and Rab GDI beta). In addition, we show that downstream protein changes can be identified in pathways corresponding to both Ube4b (including UBE1) and Nmnat1 (including VDAC1 and Aralar1) components of the chimeric Wlds gene, suggesting that full-length Wlds protein is required to elicit maximal changes in synaptic proteins. We conclude that altered mitochondrial responses to degenerative stimuli are likely to play an important role in the neuroprotective Wlds phenotype and that targeting proteins identified in the current study may lead to novel therapies for the treatment of neurodegenerative diseases in humans.
PMCID: PMC2225590  PMID: 17470424

Results 1-5 (5)