Distinct Developmental Features of Olfactory Bulb Interneurons

The olfactory bulb (OB) has an extremely higher proportionof interneurons innervating excitatory neurons than otherbrain regions, which is evolutionally conserved across species.Despite the abundance of OB interneurons, little is knownabout the diversification and physiological functions ofOB interneurons compared to cortical interneurons. In thisreview, an overview of the general developmental processof interneurons from the angles of the spatial and temporalspecifications was presented. Then, the distinct featuresshown exclusively in OB interneurons development andmolecular machinery recently identified were discussed.Finally, we proposed an evolutionary meaning for thediversity of OB interneurons.1

Odor habituation can modulate very early olfactory event-related potential

Odor habituation is a phenomenon that after repeated exposure to an odor, is characterized by decreased responses to it. The central nervous system is involved in odor habituation. To study odor habituation in humans, measurement of event-related potentials (ERPs) has been widely used in the olfactory system and other sensory systems, because of their high temporal resolution. Most previous odor habituation studies have measured the olfactory ERPs of (200–800) ms. However, several studies have shown that the odor signal is processed in the central nervous system earlier than at 200 ms. For these reasons, we studied whether when odors were habituated, olfactory ERP within 200 ms of odors could change. To this end, we performed an odor habituation behavior test and electroencephalogram experiments. In the behavior test, under habituation conditions, odor intensity was significantly decreased. We found significant differences in the negative and positive potentials within 200 ms across the conditions, which correlated significantly with the results of the behavior test. We also observed that ERP latency depended on the conditions. Our study suggests that odor habituation can involve the olfactory ERP of odors within 200 ms in the brain. © 2020, The Author(s).1

Mild Hypothermia Attenuates Intercellular Adhesion Molecule-1 Induction via Activation of Extracellular Signal-Regulated Kinase-1/2 in a Focal Cerebral Ischemia Model

Intercellular adhesion molecule-1 (ICAM-1) in cerebral vascular endothelium induced by ischemic insult triggers leukocyte infiltration and inflammatory reaction. We investigated the mechanism of hypothermic suppression of ICAM-1 in a model of focal cerebral ischemia. Rats underwent 2 hours of middle cerebral artery occlusion and were kept at 37°C or 33°C during occlusion and rewarmed to normal temperature immediately after reperfusion. Under hypothermic condition, robust activation of extracellular signal-regulated kinase-1/2 (ERK1/2) was observed in vascular endothelium of ischemic brain. Hypothermic suppression of ICAM-1 was reversed by ERK1/2 inhibition. Phosphorylation of signal transducer and activator of transcription 3 (STAT3) in ischemic vessel was attenuated by hypothermia. STAT3 inhibitor suppressed ICAM-1 production induced by stroke. ERK1/2 inhibition enhanced phosphorylation and DNA binding activity of STAT3 in hypothermic condition. In this study, we demonstrated that hypothermic suppression of ICAM-1 induction is mediated by enhanced ERK1/2 activation and subsequent attenuation of STAT3 action

Serum Tau Proteins as Potential Biomarkers for the Assessment of Alzheimer's Disease Progression

Total tau (t‐tau) and phosphorylated tau (p‐tau) protein elevations in cerebrospinal fluid (CFS) are well‐established hallmarks of Alzheimer’s disease (AD), while the associations of serum t‐tau and p‐tau levels with AD have been inconsistent across studies. To identify more accessible non‐invasive AD biomarkers, we measured serum tau proteins and associations with cognitive function in age‐matched controls (AMC, n = 26), mild cognitive impairment group (MCI, n = 30), and mild‐AD group (n = 20) according to the Mini‐mental State Examination (MMSE), Clinical Dementia Rating (CDR), and Global Deterioration Scale (GDS) scores. Serum t‐tau, but not p‐tau, was significantly higher in the mild‐AD group than AMC subjects (p < 0.05), and there were significant correlations of serum t‐tau with MMSE and GDS scores. Receiver operating characteristic (ROC) analysis distinguished mild‐AD from AMC subjects with moderate sensitivity and specificity (AUC = 0.675). We speculated that tau proteins in neuronal cell‐derived exosomes (NEX) isolated from serum would be more strongly associated with brain tau levels and disease characteristics, as these exosomes can penetrate the blood‐brain barrier. Indeed, ELISA and Western blotting indicated that both NEX t‐tau and p‐tau (S202) were significantly higher in the mild‐AD group compared to AMC (p < 0.05) and MCI groups (p < 0.01). In contrast, serum amyloid β (Aβ1–42) was lower in the mild‐AD group compared to MCI groups (p < 0.001). During the 4‐year follow‐up, NEX t‐tau and p‐tau (S202) levels were correlated with the changes in GDS and MMSE scores. In JNPL3 transgenic (Tg) mice expressing a human tau mutation, t‐tau and p‐tau expression levels in NEX increased with neuropathological progression, and NEX tau was correlated with tau in brain tissue exosomes (tEX), suggesting that tau proteins reach the circulation via exosomes. Taken together, our data suggest that serum tau proteins, especially NEX tau proteins, are useful biomarkers for monitoring AD progression. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.1

Fabrication and Characterization of Magnetic Microrobots for Three-Dimensional Cell Culture and Targeted Transportation

Magnetically manipulated microrobots are demonstrated for targeted cell transportation. Full three‐dimensional (3D) porous structures are fabricated with an SU‐8 photoresist using a 3D laser lithography system. Nickel and titanium are deposited as a magnetic material and biocompatible material, respectively. The fabricated microrobots are controlled in the fluid by external magnetic fields. Human embryonic kidney 239 (HEK 239) cells are cultivated in the microrobot to show the possibility for targeted cell transportation

Sensory Stimulation-dependent Npas4 Expression in the Olfactory Bulb during Early Postnatal Development

The development of the olfactory system is influenced by sensory inputs, and it maintains neuronal generation and plasticity throughout the lifespan. The olfactory bulb contains a higher proportion of interneurons than other brain regions, particularly during the early postnatal period of neurogenesis. Although the relationship between sensory stimulation and olfactory bulb development during the postnatal period has been well studied, the molecular mechanisms have yet to be identified. In this study, we used western blotting and immunohistochemistry to analyze the expression of the transcription factor Npas4, a neuron-specific immediate-early gene that acts as a developmental regulator in many brain regions. We found that Npas4 is highly expressed in olfactory bulb interneurons during the early postnatal stages and gradually decreases toward the late postnatal stages. Npas4 expression was observed in all olfactory bulb layers, including the rostral migratory stream, where newborn neurons are generated and migrate to the olfactory bulb. Under sensory deprivation, the olfactory bulb size and the number of olfactory bulb interneurons were reduced. Furthermore, Npas4 expression and the expression of putative Npas4 downstream molecules were decreased. Collectively, these findings indicate that Npas4 expression induced by sensory input plays a role in the formation of neural circuits with excitatory mitral/tufted cells by regulating the survival of olfactory bulb interneurons during the early stages of postnatal development. © The Korean Society for Brain and Neural Sciences. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.TRUEsciescopuskc

The erythropoietin-derived peptide MK-X and erythropoietin have neuroprotective effects against ischemic brain damage

Erythropoietin (EPO) has been well known as a hematopoietic cytokine over the past decades. However, recent reports have demonstrated that EPO plays a neuroprotective role in the central nervous system, and EPO has been considered as a therapeutic target in neurodegenerative diseases such as ischemic stroke. Despite the neuroprotective effect of EPO, clinical trials have shown its unexpected side effects, including undesirable proliferative effects such as erythropoiesis and tumor growth. Therefore, the development of EPO analogs that would confer neuroprotection without adverse effects has been attempted. In this study, we examined the potential of a novel EPO-based short peptide, MK-X, as a novel drug for stroke treatment in comparison with EPO. We found that MK-X administration with reperfusion dramatically reduced brain injury in an in vivo mouse model of ischemic stroke induced by middle cerebral artery occlusion, whereas EPO had little effect. Similar to EPO, MK-X efficiently ameliorated mitochondrial dysfunction followed by neuronal death caused by glutamate-induced oxidative stress in cultured neurons. Consistent with this effect, MK-X significantly decreased caspase-3 cleavage and nuclear translocation of apoptosis-inducing factor induced by glutamate. MK-X completely mimicked the effect of EPO on multiple activation of JAK2 and its downstream PI3K/AKT and ERK1/2 signaling pathways, and this signaling process was involved in the neuroprotective effect of MK-X. Furthermore, MK-X and EPO induced similar changes in the gene expression patterns under glutamate-induced excitotoxicity. Interestingly, the most significant difference between MK-X and EPO was that MK-X better penetrated into the brain across the brain-blood barrier than did EPO. In conclusion, we suggest that MK-X might be used as a novel drug for protection from brain injury caused by ischemic stroke, which penetrates into the brain faster in comparison with EPO, even though MK-X and EPO have similar protective effects against excitotoxicity.1

Tactile Avatar: Tactile Sensing System Mimicking Human Tactile Cognition

As a surrogate for human tactile cognition, an artificial tactile perception and cognition system are proposed to produce smooth/soft and rough tactile sensations by its user's tactile feeling; and named this system as “tactile avatar”. A piezoelectric tactile sensor is developed to record dynamically various physical information such as pressure, temperature, hardness, sliding velocity, and surface topography. For artificial tactile cognition, the tactile feeling of humans to various tactile materials ranging from smooth/soft to rough are assessed and found variation among participants. Because tactile responses vary among humans, a deep learning structure is designed to allow personalization through training based on individualized histograms of human tactile cognition and recording physical tactile information. The decision error in each avatar system is less than 2% when 42 materials are used to measure the tactile data with 100 trials for each material under 1.2N of contact force with 4cm s−1 of sliding velocity. As a tactile avatar, the machine categorizes newly experienced materials based on the tactile knowledge obtained from training data. The tactile sensation showed a high correlation with the specific user's tendency. This approach can be applied to electronic devices with tactile emotional exchange capabilities, as well as advanced digital experiences. © 2021 The Authors. Advanced Science published by Wiley-VCH GmbH1

Subthreshold electrical stimulation as a low power electrical treatment for stroke rehabilitation

As a promising future treatment for stroke rehabilitation, researchers have developed direct brain stimulation to manipulate the neural excitability. However, there has been less interest in energy consumption and unexpected side effect caused by electrical stimulation to bring functional recovery for stroke rehabilitation. In this study, we propose an engineering approach with subthreshold electrical stimulation (STES) to bring functional recovery. Here, we show a low level of electrical stimulation boosted causal excitation in connected neurons and strengthened the synaptic weight in a simulation study. We found that STES with motor training enhanced functional recovery after stroke in vivo. STES was shown to induce neural reconstruction, indicated by higher neurite expression in the stimulated regions and correlated changes in behavioral performance and neural spike firing pattern during the rehabilitation process. This will reduce the energy consumption of implantable devices and the side effects caused by stimulating unwanted brain regions. © 2021, The Author(s).1