Frontiers in neuroscience
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Frontiers in neuroscience · Jan 2020
ReviewGABAergic Inhibitory Interneuron Deficits in Alzheimer's Disease: Implications for Treatment.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized clinically by severe cognitive deficits and pathologically by amyloid plaques, neuronal loss, and neurofibrillary tangles. Abnormal amyloid β-protein (Aβ) deposition in the brain is often thought of as a major initiating factor in AD neuropathology. However, gamma-aminobutyric acid (GABA) inhibitory interneurons are resistant to Aβ deposition, and Aβ decreases synaptic glutamatergic transmission to decrease neural network activity. ⋯ Here we describe the roles played by excitatory neurons and GABA inhibitory interneurons in Aβ-induced cognitive deficits and how altered GABA interneurons regulate AD neuropathology. We also comprehensively review recent studies on how GABA interneurons and GABA receptors can be exploited for therapeutic benefit. GABA interneurons are an emerging therapeutic target in AD, with further clinical trials urgently warranted.
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Frontiers in neuroscience · Jan 2020
ReviewCritical Review of Transcutaneous Vagus Nerve Stimulation: Challenges for Translation to Clinical Practice.
Several studies have illustrated that transcutaneous vagus nerve stimulation (tVNS) can elicit therapeutic effects that are similar to those produced by its invasive counterpart, vagus nerve stimulation (VNS). VNS is an FDA-approved therapy for the treatment of both depression and epilepsy, but it is limited to the management of more severe, intervention-resistant cases as a second or third-line treatment option due to perioperative risks involved with device implantation. In contrast, tVNS is a non-invasive technique that involves the application of electrical currents through surface electrodes at select locations, most commonly targeting the auricular branch of the vagus nerve (ABVN) and the cervical branch of the vagus nerve in the neck. ⋯ As most of the described methods differ in the parameters and protocols applied, there is currently no firm evidence on the optimal location for tVNS or the stimulation parameters that provide the greatest therapeutic effects for a specific condition. This review presents the current status of tVNS with a focus on stimulation parameters, stimulation sites, and available devices. For tVNS to reach its full potential as a non-invasive and clinically relevant therapy, it is imperative that systematic studies be undertaken to reveal the mechanism of action and optimal stimulation modalities.
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Frontiers in neuroscience · Jan 2020
The Effect and Optimal Dosage of Dexmedetomidine Plus Sufentanil for Postoperative Analgesia in Elderly Patients With Postoperative Delirium and Early Postoperative Cognitive Dysfunction: A Single-Center, Prospective, Randomized, Double-Blind, Controlled Trial.
Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are common complications after major surgery among elderly patients. Dexmedetomidine (DEX) is less frequently explored for its effects in patients with postoperative neurocognitive disorders. This study investigated the effect and optimal dosage of DEX for patient-controlled analgesia (PCA) on POD and early POCD after major surgery among elderly patients. ⋯ The continuous infusion of DEX 200 μg or DEX 400 μg in PCA significantly decreased the incidence of POD and early POCD after major surgery without increasing any side effects. Compared with DEX 200 μg, DEX 400 μg was preferred for reducing early POCD in patients who underwent open surgery.
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Frontiers in neuroscience · Jan 2020
Toward Establishing Internal Validity for Correlated Gene Expression Measures in Imaging Genomics of Functional Networks: Why Distance Corrections and External Face Validity Alone Fall Short. Reply to "Distance Is Not Everything in Imaging Genomics of Functional Networks: Reply to a Commentary on Correlated Gene Expression Supports Synchronous Activity in Brain Networks".
The primary claim of the Richiardi et al. (2015) Science article is that a measure of correlated gene expression, significant strength fraction (SSF), is related to resting state fMRI (rsfMRI) networks. However, there is still debate about this claim and whether spatial proximity, in the form of contiguous clusters, accounts entirely, or only partially, for SSF (Pantazatos and Li, 2017; Richiardi et al., 2017). Here, 13 distributed networks were simulated by combining 34 contiguous clusters randomly placed throughout cortex, with resulting edge distance distributions similar to rsfMRI networks. ⋯ In conclusion, SSF is unrelated to rsfMRI networks. The main conclusion of Richiardi et al. (2015) is based on a finding that is ∼50% likely to be a false positive, not <0.01% as originally reported in the article (Richiardi et al., 2015). We discuss why distance corrections alone and external face validity are insufficient to establish a trustworthy relationship between correlated gene expression measures and rsfMRI networks, and propose more rigorous approaches to preclude common pitfalls in related studies.
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Frontiers in neuroscience · Jan 2020
Cutaneous Aβ-Non-nociceptive, but Not C-Nociceptive, Dorsal Root Ganglion Neurons Exhibit Spontaneous Activity in the Streptozotocin Rat Model of Painful Diabetic Neuropathy in vivo.
Diabetic peripheral neuropathic pain (DPNP) is the most devastating complication of diabetes mellitus. Unfortunately, successful therapy for DPNP remains a challenge because its pathogenesis is still elusive. ⋯ Compared with control, we found in STZ-rats with established pain hypersensitivity (5 weeks post-STZ) several significant changes including: (a) A 23% increase in the incidence of spontaneous activity (SA) in Aβ-LTMs (but not C-mechanosensitive nociceptors) that may cause dysesthesias/paresthesia suffered by DPNP patients, (b) membrane hyperpolarization and a ∼85% reduction in SA rate in Aβ-LTMs by Kv7 channel activation with retigabine (6 mg/kg, i.v.) suggesting that Kv7/M channels may be involved in mechanisms of SA generation in Aβ-LTMs, (c) decreases in AP duration and in duration and amplitude of afterhyperpolarization (AHP) in C-and/or Aβ-nociceptors. These faster AP and AHP kinetics may lead to repetitive firing and an increase in afferent input to the CNS and thereby contribute to DPNP development, and (d) a decrease in the electrical thresholds of Aβ-nociceptors that may contribute to their sensitization, and thus to the resulting hypersensitivity associated with DPNP.