Sulbactam improves binding property and uptake capacity of glutamate transporter-1 and decreases glutamate concentration in the CA1 region of hippocampus of global brain ischemic rats

Amino Acids ◽  
2021 ◽  
Author(s):  
Wei-Wei Gu ◽  
Xin Cui ◽  
Li-Zhe Liu ◽  
Min Zhang ◽  
Xiao-Hui Xian ◽  
...  
Keyword(s):  
Glutamate Transporter ◽  
Binding Property ◽  
Uptake Capacity ◽  
Glutamate Concentration ◽  
Ca1 Region ◽  
Glutamate Transporter 1 ◽  
Global Brain

scholarly journals Ischemia-Induced Cognitive Impairment Is Improved via Remyelination and Restoration of Synaptic Density in the Hippocampus after Treatment with COG-Up® in a Gerbil Model of Ischemic Stroke

2021 ◽  
Vol 8 (12) ◽  
pp. 321
Author(s):  
Tae-Kyeong Lee ◽  
Junkee Hong ◽  
Ji-Won Lee ◽  
Sung-Su Kim ◽  
Hyejin Sim ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cognitive Impairment ◽  
Myelin Basic Protein ◽  
Basic Protein ◽  
Glutamate Transporter ◽  
Vesicular Glutamate Transporter ◽  
Synaptic Density ◽  
Ca1 Region ◽  
Fluoro Jade B ◽  
Glutamate Transporter 1

Cerebrovascular disease such as ischemic stroke develops cognitive impairment due to brain tissue damage including neural loss, demyelination and decrease in synaptic density. In the present study, we developed transient ischemia in the forebrain of the gerbil and found cognitive impairment using the Barnes maze test and passive avoidance test for spatial memory and learning memory, respectively. In addition, neuronal loss/death was detected in the Cornu Ammonis 1 (CA1) region of the gerbil hippocampus after the ischemia by cresyl violet histochemistry, immunohistochemistry for neuronal nuclei and histofluorescence with Fluoro-Jade B. Furthermore, in the CA1 region following ischemia, myelin and vesicular synaptic density were significantly decreased using immunohistochemistry for myelin basic protein and vesicular glutamate transporter 1. In the gerbils, treatment with COG-up® (a combined extract of Erigeron annuus (L.) Pers. and Brassica oleracea Var.), which was rich in scutellarin and sinapic acid, after the ischemia, significantly improved ischemia-induced decline in memory function when compared with that shown in gerbils treated with vehicle after the ischemia. In the CA1 region of these gerbils, COG-up® treatment significantly promoted the remyelination visualized using immunohistochemistry myelin basic protein, increased oligodendrocytes visualized using a receptor-interacting protein, and restored the density of glutamatergic synapses visualized using double immunofluorescence for vesicular glutamate transporter 1 and microtubule-associated protein, although COG-up® treatment did not protect pyramidal cells (principal neurons) located in the CA1 region form the ischemic insult. Considering the current findings, a gerbil model of ischemic stroke apparently showed cognitive impairment accompanied by ischemic injury in the hippocampus; also, COG-up® can be employed for improving cognitive decline following ischemia-reperfusion injury in brains.

scholarly journals Endocytosis of the glutamate transporter 1 is regulated by laforin and malin: Implications in Lafora disease

Glia ◽  
2020 ◽  
Author(s):  
Eva Perez‐Jimenez ◽  
Rosa Viana ◽  
Carmen Muñoz‐Ballester ◽  
Carlos Vendrell‐Tornero ◽  
Raquel Moll‐Diaz ◽  
...  
Keyword(s):  
Glutamate Transporter ◽  
Lafora Disease ◽  
Glutamate Transporter 1

scholarly journals Activation of Glutamate Transporter-1 (GLT-1) Confers Sex-Dependent Neuroprotection in Brain Ischemia

2021 ◽  
Vol 11 (1) ◽  
pp. 76
Author(s):  
Flavia A. Tejeda-Bayron ◽  
David E. Rivera-Aponte ◽  
Christian J. Malpica-Nieves ◽  
Gerónimo Maldonado-Martínez ◽  
Héctor M. Maldonado ◽  
...  
Keyword(s):  
Infarct Size ◽  
Glutamate Transporter ◽  
Triphenyltetrazolium Chloride ◽  
Stroke Outcomes ◽  
Female Mice ◽  
Protein Levels ◽  
Translational Activator ◽  
Glutamate Transporter 1 ◽  
Sensorimotor Performance

Stroke is one of the leading causes of long-term disability. During ischemic stroke, glutamate is released, reuptake processes are impaired, and glutamate promotes excitotoxic neuronal death. Astrocytic glutamate transporter 1 (GLT-1) is the major transporter responsible for removing excess glutamate from the extracellular space. A translational activator of GLT-1, LDN/OSU 0212320 (LDN) has been previously developed with beneficial outcomes in epileptic animal models but has never been tested as a potential therapeutic for ischemic strokes. The present study evaluated the effects of LDN on stroke-associated brain injury. Male and female mice received LDN or vehicle 24 h before or 2 h after focal ischemia was induced in the sensorimotor cortex. Sensorimotor performance was determined using the Rung Ladder Walk and infarct area was assessed using triphenyltetrazolium chloride staining. Males treated with LDN exhibited upregulated GLT-1 protein levels, significantly smaller infarct size, and displayed better sensorimotor performance in comparison to those treated with vehicle only. In contrast, there was no upregulation of GLT-1 protein levels and no difference in infarct size or sensorimotor performance between vehicle- and LDN-treated females. Taken together, our results indicate that the GLT-1 translational activator LDN improved stroke outcomes in young adult male, but not female mice.

scholarly journals Altered dopaminergic pathways and therapeutic effects of intranasal dopamine in two distinct mouse models of autism

2020 ◽  
Author(s):  
Owen Y Chao ◽  
Salil S Pathak ◽  
Hao Zhang ◽  
Nathan Dunaway ◽  
Jay-Shake Li ◽  
...  
Keyword(s):  
Fragile X ◽  
Glutamate Transporter ◽  
Dorsal Striatum ◽  
Autism Spectrum ◽  
Acid Decarboxylase ◽  
Therapeutic Effects ◽  
Spatial Coupling ◽  
Motivated Behavior ◽  
Object Based ◽  
Glutamate Transporter 1

Abstract The dopamine (DA) system has a profound impact on reward-motivated behavior and is critically involved in neurodevelopmental disorders, such as autism spectrum disorder (ASD). Although DA defects are found in autistic patients, it is not well defined how the DA pathways are altered in ASD and whether DA can be utilized as a potential therapeutic agent for ASD. To this end, we employed a phenotypic and a genetic ASD model, i.e., Black and Tan BRachyury T+Itpr3tf/J (BTBR) mice and Fragile X Mental Retardation 1 knockout (Fmr1-KO) mice, respectively. Immunostaining of tyrosine hydroxylase (TH) to mark dopaminergic neurons revealed an overall reduction in the TH expression in the substantia nigra, ventral tegmental area and dorsal striatum of BTBR mice, as compared to C57BL/6J wild-type ones. In contrast, Fmr1-KO animals did not show such an alteration but displayed abnormal morphology of TH-positive axons in the striatum with higher “complexity” and lower “texture”. Both strains exhibited decreased expression of striatal dopamine transporter (DAT) and increased spatial coupling between vesicular glutamate transporter 1 (VGLUT1, a label for glutamatergic terminals) and TH signals, while GABAergic neurons quantified by glutamic acid decarboxylase 67 (GAD67) remained intact. Intranasal administration of DA rescued the deficits in non-selective attention, object-based attention and social approaching of BTBR mice, likely by enhancing the level of TH in the striatum. Application of intranasal DA to Fmr1-KO animals alleviated their impairment of social novelty, in association with reduced striatal TH protein. These results suggest that although the DA system is modified differently in the two ASD models, intranasal treatment with DA effectively rectifies their behavioral phenotypes, which may present a promising therapy for diverse types of ASD.

scholarly journals Effects of Repeated 20-Hz Electrical Stimulation on Functional Recovery Following Peripheral Nerve Injury

2019 ◽  
Vol 33 (9) ◽  
pp. 775-784 ◽  
Author(s):  
Sohee Park ◽  
Cai-yue Liu ◽  
Patricia J. Ward ◽  
Poonam B. Jaiswal ◽  
Arthur W. English
Keyword(s):  
Electrical Stimulation ◽  
Peripheral Nerves ◽  
Treadmill Exercise ◽  
Glutamate Transporter ◽  
Vesicular Glutamate Transporter ◽  
Single Application ◽  
Repeated Applications ◽  
Peripheral Axon ◽  
Glutamate Transporter 1 ◽  
Muscle Responses

One hour of 20-Hz continuous electrical stimulation (ES) applied at the time of injury promotes the regeneration of axons in cut peripheral nerves. A more robust enhancement of peripheral axon regeneration is achieved by 2 weeks of daily treadmill exercise. We investigated whether repeated applications of brief ES (mES) would be more effective in promoting regeneration than a single application. Sciatic nerves of C57B6 mice were cut and repaired by end-to-end anastomosis. At that time and every third day for 2 weeks, the repaired nerve was stimulated for 1 hour at 20 Hz. In controls, injured mice were either untreated or treated with ES only once. Direct muscle responses recorded from reinnervated muscles in awake animals were observed earlier both in mice treated with ES and mES than untreated controls. Their amplitudes increased progressively over the post transection study period, but the rate of this progression was increased significantly only in animals treated once with ES. Monosynaptic H reflexes recovered to pretransection levels in both untreated and singly treated mice but in the animals treated repeatedly, they were maintained at more than twice that of the same reflexes recorded prior to injury. In anatomical analyses, both excitatory and inhibitory synaptic contacts with the cell bodies of injured motoneurons, including those expressing the vesicular glutamate transporter 1 (VGLUT1), were sustained in mice treated repeatedly but not in singly treated or untreated mice. Repeated ES does not enhance the rate of restoration of functional muscle reinnervation and results in the retention of exaggerated reflexes.

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