Zinc Homeostasis and Neurodegenerative Disorders.

Zinc homeostasis and neurodegenerative disorders.

Front Aging Neurosci. 2013; 5: 33
Szewczyk B

Zinc is an essential trace element, whose importance to the function of the central nervous system (CNS) is increasingly being appreciated. Alterations in zinc dyshomeostasis has been suggested as a key factor in the development of several neuropsychiatric disorders. In the CNS, zinc occurs in two forms: the first being tightly bound to proteins and, secondly, the free, cytoplasmic, or extracellular form found in presynaptic vesicles. Under normal conditions, zinc released from the synaptic vesicles modulates both ionotropic and metabotropic post-synaptic receptors. While under clinical conditions such as traumatic brain injury, stroke or epilepsy, the excess influx of zinc into neurons has been found to result in neurotoxicity and damage to postsynaptic neurons. On the other hand, a growing body of evidence suggests that a deficiency, rather than an excess, of zinc leads to an increased risk for the development of neurological disorders. Indeed, zinc deficiency has been shown to affect neurogenesis and increase neuronal apoptosis, which can lead to learning and memory deficits. Altered zinc homeostasis is also suggested as a risk factor for depression, Alzheimer’s disease (AD), aging, and other neurodegenerative disorders. Under normal CNS physiology, homeostatic controls are put in place to avoid the accumulation of excess zinc or its deficiency. This cellular zinc homeostasis results from the actions of a coordinated regulation effected by different proteins involved in the uptake, excretion and intracellular storage/trafficking of zinc. These proteins include membranous transporters (ZnT and Zip) and metallothioneins (MT) which control intracellular zinc levels. Interestingly, alterations in ZnT and MT have been recently reported in both aging and AD. This paper provides an overview of both clinical and experimental evidence that implicates a dysfunction in zinc homeostasis in the pathophysiology of depression, AD, and aging. HubMed – depression

Modulation of epileptic activity by deep brain stimulation: a model-based study of frequency-dependent effects.

Front Comput Neurosci. 2013; 7: 94
Mina F, Benquet P, Pasnicu A, Biraben A, Wendling F

A number of studies showed that deep brain stimulation (DBS) can modulate the activity in the epileptic brain and that a decrease of seizures can be achieved in “responding” patients. In most of these studies, the choice of stimulation parameters is critical to obtain desired clinical effects. In particular, the stimulation frequency is a key parameter that is difficult to tune. A reason is that our knowledge about the frequency-dependant mechanisms according to which DBS indirectly impacts the dynamics of pathological neuronal systems located in the neocortex is still limited. We address this issue using both computational modeling and intracerebral EEG (iEEG) data. We developed a macroscopic (neural mass) model of the thalamocortical network. In line with already-existing models, it includes interconnected neocortical pyramidal cells and interneurons, thalamocortical cells and reticular neurons. The novelty was to introduce, in the thalamic compartment, the biophysical effects of direct stimulation. Regarding clinical data, we used a quite unique data set recorded in a patient (drug-resistant epilepsy) with a focal cortical dysplasia (FCD). In this patient, DBS strongly reduced the sustained epileptic activity of the FCD for low-frequency (LFS, < 2 Hz) and high-frequency stimulation (HFS, > 70 Hz) while intermediate-frequency stimulation (IFS, around 50 Hz) had no effect. Signal processing, clustering, and optimization techniques allowed us to identify the necessary conditions for reproducing, in the model, the observed frequency-dependent stimulation effects. Key elements which explain the suppression of epileptic activity in the FCD include: (a) feed-forward inhibition and synaptic short-term depression of thalamocortical connections at LFS, and (b) inhibition of the thalamic output at HFS. Conversely, modeling results indicate that IFS favors thalamic oscillations and entrains epileptic dynamics. HubMed – depression

A comprehensive review of auditory verbal hallucinations: lifetime prevalence, correlates and mechanisms in healthy and clinical individuals.

Front Hum Neurosci. 2013; 7: 367
de Leede-Smith S, Barkus E

Over the years, the prevalence of auditory verbal hallucinations (AVHs) have been documented across the lifespan in varied contexts, and with a range of potential long-term outcomes. Initially the emphasis focused on whether AVHs conferred risk for psychosis. However, recent research has identified significant differences in the presentation and outcomes of AVH in patients compared to those in non-clinical populations. For this reason, it has been suggested that auditory hallucinations are an entity by themselves and not necessarily indicative of transition along the psychosis continuum. This review will examine the presentation of auditory hallucinations across the life span, as well as in various clinical groups. The stages described include childhood, adolescence, adult non-clinical populations, hypnagogic/hypnopompic experiences, high schizotypal traits, schizophrenia, substance induced AVH, AVH in epilepsy, and AVH in the elderly. In children, need for care depends upon whether the child associates the voice with negative beliefs, appraisals and other symptoms of psychosis. This theme appears to carry right through to healthy voice hearers in adulthood, in which a negative impact of the voice usually only exists if the individual has negative experiences as a result of their voice(s). This includes features of the voices such as the negative content, frequency, and emotional valence as well as anxiety and depression, independently or caused by voices presence. It seems possible that the mechanisms which maintain AVH in non-clinical populations are different from those which are behind AVH presentations in psychotic illness. For example, the existence of maladaptive coping strategies in patient populations is one significant difference between clinical and non-clinical groups which is associated with a need for care. Whether or not these mechanisms start out the same and have differential trajectories is not yet evidenced. Future research needs to focus on the comparison of underlying factors and mechanisms that lead to the onset of AVH in both patient and non-clinical populations. HubMed – depression