Neuroscience
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An intriguing feature of nervous system development in most animal species is that the initial number of generated neurons is higher than the number of neurons incorporated into mature circuits. A substantial portion of neurons is indeed eliminated via apoptosis during a short time window - in rodents the first two postnatal weeks. ⋯ In postnatal rodent neocortex, the peak of apoptosis coincides with the occurrence of spontaneous, synchronous activity patterns. In this article, we review recent results that demonstrate the important role of electrical activity for neuronal survival in the neocortex, describe the role of Ca2+ and neurotrophic factors in translating electrical activity into pro-survival signals, and finally discuss the clinical impact of the tight relation between electrical activity and neuronal survival versus apoptosis.
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Randomized Controlled Trial
Role of capsaicin- and heat-sensitive afferents in stimulation of acupoint induced pain and analgesia in humans.
We investigated role of capsaicin-sensitive afferents within and without the areas of Zusanli (ST36)/Shangjuxu (ST37) acupoints along the stomach (ST) meridian in the perception and modulation of pain assessed by visual analog scale of pain and its distribution rated by subjects, pressure pain threshold (PPT), and heat pain threshold (HPT) in humans. Compared with the treatment of non-acupoint area, capsaicin (100µg/50µl) administered into either ST36 or ST37 acupoint caused the strongest pain intensity and the most extensive pain distribution, followed by rapid onset, bilateral, long-lasting secondary mechanical hyperalgesia and slower onset secondary heat hypoalgesia (1day after the capsaicin treatment). ⋯ Upon trapezius muscle pain elicited by the i.m. injection of 5.8% saline, pre-emptive treatment of the contralateral ST36 acupoint with 43°C heating-needle stimulation alleviated the ongoing muscle pain, reduced painful area, and reversed the decrease in HPT. It is suggested that (1) pain elicited from the acupoint and non-acupoint areas differs significantly, which are supposed to be dependent on the different distributions and contributions of capsaicin-sensitive afferents. (2) Non-painful heat stimulation is a valid approach in prevention of ongoing muscle pain with associated post-effects of peripheral and central sensitization.
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Epilepsy is one of the most common chronic neurological conditions worldwide. The current poor understanding and lack of reliable biomarkers of the epileptogenic process are the major limitations in the development of anti-epileptic drugs that are able to prevent or modify the underlying disease. ⋯ Here we review the advances of different in vivo imaging techniques, including magnetic resonance-based and nuclear imaging-based modalities, in animal models of epilepsy. Together these techniques can be applied to visualize and quantify structural, metabolic, functional and molecular changes in longitudinal study designs to provide unique information about early pathophysiological changes and their interplay involved in epileptogenesis, monitoring the disease progression, assessing the effectiveness of possible therapies, and potentially identify translatable biomarkers for clinical use.
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Parkinson's disease (PD) is characterized by the formation of Lewy bodies (LBs) in dopaminergic neurons. α-Synuclein (α-syn), a major protein component of LBs, is known to regulate synaptic plasticity, with a crucial role in memory and motor function in the central nervous system. Levodopa (L-3,4-dihydroxyphenylalanine; also known as L-DOPA) is considered the most effective medication for controlling the symptoms of PD. However, it is unclear whether L-DOPA improves the neuropathology of PD. ⋯ Our data showed that L-DOPA could attenuate ER stress markers, including the levels of activating transcription factor 4 (ATF4), C/EBPhomologous protein expression (CHOP), immunoglobulin-heavy-chain-binding protein (BiP), sliced X-box-binding protein 1 (XBP-1), and reduce nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling through dopamine receptor D2 (DRD2) in SH-SY5Y neuronal cells under α-syn-induced toxicity. In conclusion, we suggest that L-DOPA may attenuate the neuropathology of PD by regulating signaling related to DRD2 in neuronal cells under α-syn-induced toxicity. Our study, therefore, indicates an additional role for L-DOPA in the treatment of PD.
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To study the development of orthographic sensitivity during elementary school, we recorded event-related brain potentials (ERPs) from 2nd and 4th grade children who were exposed to line drawing of object or animals upon which the correctly or incorrectly spelled name was superimposed. Stimulus-locked ERPs showed a modulation of a frontocentral negativity between 200 and 500ms which was larger for the 4th grade children but did not show an effect of correctness of spelling. This effect was followed by a pronounced positive shift which was only seen in the 4th grade children and which showed a modulation of spelling correctness. ⋯ Moreover, response-locked ERPs triggered to the children's button presses indicating orthographic (in)-correctness showed a succession of waves including the frontocentral error-related negativity and a subsequent negativity with a more posterior distribution. This latter negativity was generally larger for the 4th grade children. Only for the 4th grade children, this negativity was smaller for the false alarm trials suggesting a conscious registration of the error in these children.