3,326 research outputs found
Effects of Pharmacological Block of GABAA Receptors on Pallidal Neurons in Normal and Parkinsonian State
The globus pallidus plays a central integrative role in the basal ganglia circuitry. Morphological studies have revealed a high level of GABA and GABAA receptors in the globus pallidus. To further investigate the effects of endogenous GABAA neurotransmission in the globus pallidus of normal and parkinsonian rats, in vivo extracellular recording and behavioral tests were performed in the present studies. In normal rats, micro-pressure ejection of GABAA receptor antagonist gabazine (0.1 mM) increased the spontaneous firing rate of pallidal neurons by 28.3%. Furthermore, in 6-hydroxydopamine parkinsonian rats, gabazine increased the firing rate by 46.0% on the lesioned side, which was significantly greater than that on the unlesioned side (21.5%, P < 0.05), as well as that in normal rats (P < 0.05). In the behaving rats, unilateral microinjection of gabazine (0.1 mM) evoked consistent contralateral rotation in normal rats, and significantly potentiated the number of apomorphine-induced contralateral rotations in parkinsonian rats. The present electrophysiological and behavioral findings may provide a rational for further investigations into the potential of pallidal endogenous GABAA neurotransmission in the treatment of Parkinson's disease
Deep brain stimulation in schizophrenia
Deep brain stimulation (DBS) has successfully advanced treatment options of putative therapy-resistant
neuropsychiatric diseases. Building on this strong foundation more and more mental disorders in the
stadium of therapy-resistance are considered as possible indications for DBS. Especially schizophrenia
with its associated severe and difficult to treat symptoms is gaining attention. This attention demands
critical questions regarding the assumed mechanisms of DBS and its possible influence on the supposed
pathophysiology of schizophrenia. Here we synoptically compare current approaches and theories of
DBS and discuss the feasibility of DBS in schizophrenia as well as the transferability from other
psychiatric disorders successfully treated with DBS. For this we consider recent advances in animal
models of schizophrenic symptoms, results regarding the influence of DBS on dopaminergic
transmission as well as data concerning neural oscillation and synchronization. In conclusion the use of
DBS for some symptoms of schizophrenia seems to be a promising approach, but the lack of a
comprehensive theory of the mechanisms of DBS as well as its impact on schizophrenia might void the
use of DBS in schizophrenia at this point
Potential mechanisms for imperfect synchronization in parkinsonian basal ganglia
Neural activity in the brain of parkinsonian patients is characterized by the
intermittently synchronized oscillatory dynamics. This imperfect
synchronization, observed in the beta frequency band, is believed to be related
to the hypokinetic motor symptoms of the disorder. Our study explores potential
mechanisms behind this intermittent synchrony. We study the response of a
bursting pallidal neuron to different patterns of synaptic input from
subthalamic nucleus (STN) neuron. We show how external globus pallidus (GPe)
neuron is sensitive to the phase of the input from the STN cell and can exhibit
intermittent phase-locking with the input in the beta band. The temporal
properties of this intermittent phase-locking show similarities to the
intermittent synchronization observed in experiments. We also study the
synchronization of GPe cells to synaptic input from the STN cell with
dependence on the dopamine-modulated parameters. Dopamine also affects the
cellular properties of neurons. We show how the changes in firing patterns of
STN neuron due to the lack of dopamine may lead to transition from a lower to a
higher coherent state, roughly matching the synchrony levels observed in basal
ganglia in normal and parkinsonian states. The intermittent nature of the
neural beta band synchrony in Parkinson's disease is achieved in the model due
to the interplay of the timing of STN input to pallidum and pallidal neuronal
dynamics, resulting in sensitivity of pallidal output to the phase of the
arriving STN input. Thus the mechanism considered here (the change in firing
pattern of subthalamic neurons through the dopamine-induced change of membrane
properties) may be one of the potential mechanisms responsible for the
generation of the intermittent synchronization observed in Parkinson's disease.Comment: 27 pages, 9 figure
Cerebral Iron Deposition in Neurodegeneration
Disruption of cerebral iron regulation appears to have a role in aging and in the pathogenesis of various neurodegenerative disorders. Possible unfavorable impacts of iron accumulation include reactive oxygen species generation, induction of ferroptosis, and acceleration of inflammatory changes. Whole-brain iron-sensitive magnetic resonance imaging (MRI) techniques allow the examination of macroscopic patterns of brain iron deposits in vivo, while modern analytical methods ex vivo enable the determination of metal-specific content inside individual cell-types, sometimes also within specific cellular compartments. The present review summarizes the whole brain, cellular, and subcellular patterns of iron accumulation in neurodegenerative diseases of genetic and sporadic origin. We also provide an update on mechanisms, biomarkers, and effects of brain iron accumulation in these disorders, focusing on recent publications. In Parkinson’s disease, Friedreich’s disease, and several disorders within the neurodegeneration with brain iron accumulation group, there is a focal siderosis, typically in regions with the most pronounced neuropathological changes. The second group of disorders including multiple sclerosis, Alzheimer’s disease, and amyotrophic lateral sclerosis shows iron accumulation in the globus pallidus, caudate, and putamen, and in specific cortical regions. Yet, other disorders such as aceruloplasminemia, neuroferritinopathy, or Wilson disease manifest with diffuse iron accumulation in the deep gray matter in a pattern comparable to or even more extensive than that observed during normal aging. On the microscopic level, brain iron deposits are present mostly in dystrophic microglia variably accompanied by iron-laden macrophages and in astrocytes, implicating a role of inflammatory changes and blood–brain barrier disturbance in iron accumulation. Options and potential benefits of iron reducing strategies in neurodegeneration are discussed. Future research investigating whether genetic predispositions play a role in brain Fe accumulation is necessary. If confirmed, the prevention of further brain Fe uptake in individuals at risk may be key for preventing neurodegenerative disorders.publishedVersio
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