scholarly journals Effects of Chronic Dopamine D2R Agonist Treatment and Polysialic Acid Depletion on Dendritic Spine Density and Excitatory Neurotransmission in the mPFC of Adult Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Esther Castillo-Gómez ◽  
Emilio Varea ◽  
José Miguel Blasco-Ibáñez ◽  
Carlos Crespo ◽  
Juan Nacher
Keyword(s):  
Pyramidal Neurons ◽  
Polysialic Acid ◽  
Glutamate Transporter ◽  
Structural Plasticity ◽  
Synaptic Function ◽  
Spine Density ◽  
Adult Rats ◽  
Altered Expression ◽  
Excitatory Neurotransmission ◽  
Glutamate Transporter 1

Dopamine D2 receptors (D2R) in the medial prefrontal cortex (mPFC) are key players in the etiology and therapeutics of schizophrenia. The overactivation of these receptors contributes to mPFC dysfunction. Chronic treatment with D2R agonists modifies the expression of molecules implicated in neuronal structural plasticity, synaptic function, and inhibitory neurotransmission, which are also altered in schizophrenia. These changes are dependent on the expression of the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), a plasticity-related molecule, but nothing is known about the effects of D2R and PSA-NCAM on excitatory neurotransmission and the structure of mPFC pyramidal neurons, two additional features affected in schizophrenia. To evaluate these parameters, we have chronically treated adult rats with PPHT (a D2R agonist) after enzymatic removal of PSA with Endo-N. Both treatments decreased spine density in apical dendrites of pyramidal neurons without affecting their inhibitory innervation. Endo-N also reduced the expression of vesicular glutamate transporter-1. These results indicate that D2R and PSA-NCAM are important players in the regulation of the structural plasticity of mPFC excitatory neurons. This is relevant to our understanding of the neurobiological basis of schizophrenia, in which structural alterations of pyramidal neurons and altered expression of D2R and PSA-NCAM have been found.

scholarly journals Endothelial Cdk5 deficit leads to the development of spontaneous epilepsy through CXCL1/CXCR2-mediated reactive astrogliosis

2019 ◽  
Vol 217 (1) ◽  
Author(s):  
Xiu-xiu Liu ◽  
Lin Yang ◽  
Ling-xiao Shao ◽  
Yang He ◽  
Gang Wu ◽  
...  
Keyword(s):  
Neuronal Excitability ◽  
Glutamate Transporter ◽  
Synaptic Function ◽  
Cyclin Dependent Kinase ◽  
Spontaneous Seizures ◽  
Glutamate Transporter 1 ◽  
Deficient Mice ◽  
Cxcl1 Expression ◽  
Cyclin Dependent Kinase 5 ◽  
Unknown Link

Blood–brain barrier (BBB) dysfunction has been suggested to play an important role in epilepsy. However, the mechanism mediating the transition from cerebrovascular damage to epilepsy remains unknown. Here, we report that endothelial cyclin-dependent kinase 5 (CDK5) is a central regulator of neuronal excitability. Endothelial-specific Cdk5 knockout led to spontaneous seizures in mice. Knockout mice showed increased endothelial chemokine (C-X-C motif) ligand 1 (Cxcl1) expression, decreased astrocytic glutamate reuptake through the glutamate transporter 1 (GLT1), and increased glutamate synaptic function. Ceftriaxone restored astrocytic GLT1 function and inhibited seizures in endothelial Cdk5-deficient mice, and these effects were also reversed after silencing Cxcl1 in endothelial cells and its receptor chemokine (C-X-C motif) receptor 2 (Cxcr2) in astrocytes, respectively, in the CA1 by AAV transfection. These results reveal a previously unknown link between cerebrovascular factors and epileptogenesis and provide a rationale for targeting endothelial signaling as a potential treatment for epilepsy.

scholarly journals Layer-Specific Vesicular Glutamate Transporter 1 Immunofluorescence Levels Delineate All Layers of the Human Hippocampus Including the Stratum lucidum

2021 ◽  
Vol 15 ◽  
Author(s):  
Sarah Woelfle ◽  
Tobias M. Boeckers
Keyword(s):  
Pyramidal Neurons ◽  
Hippocampal Formation ◽  
Glutamate Transporter ◽  
Mossy Fibers ◽  
Vesicular Glutamate Transporter ◽  
Nissl Staining ◽  
Clear Cut ◽  
Human Hippocampus ◽  
Stratum Lucidum ◽  
Glutamate Transporter 1

The hippocampal formation consists of the Ammon’s horn (cornu Ammonis with its regions CA1-4), dentate gyrus, subiculum, and the entorhinal cortex. The rough extension of the regions CA1-3 is typically defined based on the density and size of the pyramidal neurons without clear-cut boundaries. Here, we propose the vesicular glutamate transporter 1 (VGLUT1) as a molecular marker for the CA3 region. This is based on its strong labeling of the stratum lucidum (SL) in fluorescently stained human hippocampus sections. VGLUT1 puncta of the intense SL band co-localize with synaptoporin (SPO), a protein enriched in mossy fibers (MFs). Owing to its specific intensity profile throughout all hippocampal layers, VGLUT1 could be implemented as a pendant to Nissl-staining in fluorescent approaches with the additional demarcation of the SL. Furthermore, by high-resolution confocal microscopy, we detected VGLUT2 in the human hippocampus, thus reconciling two previous studies. Finally, by VGLUT1/SPO co-staining, we provide evidence for the existence of infrapyramidal MFs in the human hippocampus and we show that SPO expression is not restricted to MF synapses as demonstrated for rodent tissue.

scholarly journals Altered Expression of the Glutamate Transporter EAAC1 in Neurons and Immature Oligodendrocytes after Transient Forebrain Ischemia

2000 ◽  
Vol 20 (4) ◽  
pp. 678-687 ◽  
Author(s):  
M. Gottlieb ◽  
M. Domercq ◽  
C. Matute
Keyword(s):  
Cerebral Cortex ◽  
Pyramidal Neurons ◽  
Glutamate Uptake ◽  
Glutamate Transporter ◽  
Subcortical White Matter ◽  
Moderate Increase ◽  
Forebrain Ischemia ◽  
Altered Expression ◽  
Transient Forebrain Ischemia ◽  
Ca1 Region

Glutamate uptake is reduced during ischemia because of perturbations of ionic gradients across neuronal and glial membranes. Using immunohistochemical and Western blot analyses, the authors examined the expression of the glutamate transporters EAAC1, GLAST, and GLT-1 in the rat hippocampus and cerebral cortex 8 hours and 1 to 28 days after transient forebrain ischemia. Densitometric analysis of immunoblots of CA1 homogenates showed a moderate increase in EAAC1 protein levels early after the insult. Consistently, it was observed that EAAC1 immunostaining in CA1 pyramidal neurons was more intense after 8 hours and 1 day of reperfusion and reduced at later postischemia stages. A similar transient increase of EAAC1 immunolabeling was detected in layer V pyramidal neurons of the cerebral cortex. In addition, the authors observed that EAAC1 also was located in oligodendroglial progenitor cells in subcortical white matter. The number of EAAC1-labeled cells in this region was increased after 3 and 28 days of reperfusion. Finally, changes in GLAST and GLT-1 expression were not observed in the CA1 region after ischemia using immunohistochemical study or immunoblotting. Enhanced expression of EAAC1 may be an adaptive response to increased levels of extracellular glutamate during ischemia.

scholarly journals The Upregulation of Glial Glutamate Transporter-1 Participates in the Induction of Brain Ischemic Tolerance in Rats

2007 ◽  
Vol 27 (7) ◽  
pp. 1352-1368 ◽  
Author(s):  
Min Zhang ◽  
Wen-Bin Li ◽  
Jin-Xia Geng ◽  
Qing-Jun Li ◽  
Xiao-Cai Sun ◽  
...  
Keyword(s):  
Neuronal Death ◽  
Pyramidal Neurons ◽  
Glutamate Transporter ◽  
Protective Role ◽  
Ischemic Tolerance ◽  
Delayed Neuronal Death ◽  
Ischemic Insult ◽  
Glial Glutamate Transporter ◽  
Glutamate Transporter 1

Glial glutamate transporter-1 (GLT-1) plays an essential role in removing glutamate from the extracellular space and maintaining the glutamate below neurotoxic level in the brain. To explore whether GLT-1 plays a role in the acquisition of brain ischemic tolerance (BIT) induced by cerebral ischemic preconditioning (CIP), the present study was undertaken to observe in vivo changes in the expression of GLT-1 and glial fibrillary acidic protein (GFAP) in the CA1 hippocampus during the induction of BIT, and the effect of dihydrokainate (DHK), an inhibitor of GLT-1, on the acquisition of BIT in rats. Immunohistochemistry for GFAP showed that the processes of astrocytes were prolonged after a CIP 2 days before the lethal ischemic insult, which could protect pyramidal neurons in the CA1 hippocampus against delayed neuronal death induced normally by lethal ischemic insult. The prolonged processes extended into the area between the pyramidal neurons and tightly surrounded them. These changes made the pyramidal layer look like a ‘shape grid’. Simultaneously, the prolonged and extended processes showed a great deal of GLT-1. Western blotting analysis showed significant upregulation of GLT-1 expression after the CIP, especially when it was administered 2 days before the subsequent lethal ischemic insult. Neuropathological evaluation by thionin staining showed that DHK dose-dependently blocked the protective role of CIP against delayed neuronal death induced normally by lethal brain ischemia. It might be concluded that the surrounding of pyramidal neurons by astrocytes and upregulation of GLT-1 induced by CIP played an important role in the acquisition of the BIT induced by CIP.

scholarly journals SNP rs10420324 in the AMPA receptor auxiliary subunit TARP γ-8 regulates the susceptibility to antisocial personality disorder

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shi-Xiao Peng ◽  
Yue-Ying Wang ◽  
Min Zhang ◽  
Yan-Yu Zang ◽  
Dan Wu ◽  
...  
Keyword(s):  
Personality Disorder ◽  
Ampa Receptors ◽  
Pyramidal Neurons ◽  
Synaptic Function ◽  
Psychiatric Disease ◽  
Quadruplex Dna ◽  
Protein Group ◽  
Excitatory Neurotransmission ◽  
Subcortical Regions

AbstractIn the brain, AMPA receptors mediate fast excitatory neurotransmission, the dysfunction of which leads to neuropsychiatric disorders. Synaptic function of AMPA receptors is tightly controlled by a protein group called transmembrane AMPAR regulatory proteins (TARPs). TARP γ-8 (also known as CACNG8) preferentially expresses in the hippocampus, cortex and subcortical regions that are critical for emotion generation indicating its association with psychiatric disorders. Here, we identified rs10420324 (T/G), a SNP located in the human CACNG8 gene, regulated reporter gene expression in vitro and TARP γ-8 expression in the human brain. A guanine at the locus (rs10420324G) suppressed transcription likely through modulation of a local G-quadruplex DNA structure. Consistent with these observations, the frequency of rs10420324G was higher in patients with anti-social personality disorder (ASPD) than in controls, indicating that rs10420324G in CACNG8 is more voluntary for ASPD. We then characterized the behavior of TARP γ-8 knockout and heterozygous mice and found that consistent with ASPD patients who often exhibit impulsivity, aggression, risk taking, irresponsibility and callousness, a decreased γ-8 expression in mice displayed similar behaviors. Furthermore, we found that a decrease in TARP γ-8 expression impaired synaptic AMPAR functions in layer 2–3 pyramidal neurons of the prefrontal cortex, a brain region that inhibition leads to aggression, thus explaining, at least partially, the neuronal basis for the behavioral abnormality. Taken together, our study indicates that TARP γ-8 expression level is associated with ASPD, and that the TARP γ-8 knockout mouse is a valuable animal model for studying this psychiatric disease.

scholarly journals Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo

2021 ◽  
Author(s):  
Ling-Xiao Shao ◽  
Clara Liao ◽  
Ian Gregg ◽  
Neil K. Savalia ◽  
Kristina Delagarza ◽  
...  
Keyword(s):  
Single Dose ◽  
Frontal Cortex ◽  
Dendritic Spines ◽  
Pyramidal Neurons ◽  
Therapeutic Potential ◽  
Structural Plasticity ◽  
Head Width ◽  
Spine Density ◽  
Synaptic Remodeling

AbstractPsilocybin is a serotonergic psychedelic with untapped therapeutic potential. Here we chronically imaged apical dendritic spines of layer 5 pyramidal neurons in mouse medial frontal cortex. We found that a single dose of psilocybin led to ∼10% increases in spine density and spine head width. Synaptic remodeling occurred quickly within 24 hours and was persistent 1 month later. The results demonstrate structural plasticity that may underpin psilocybin’s long-lasting beneficial actions.

In Vivo Demonstration of a Late Depolarizing Postsynaptic Potential in CA1 Pyramidal Neurons

2005 ◽  
Vol 93 (3) ◽  
pp. 1326-1335 ◽  
Author(s):  
Yuan Fan ◽  
Bende Zou ◽  
Yiwen Ruan ◽  
Zhiping Pang ◽  
Zao C. Xu
Keyword(s):  
Nmda Receptor ◽  
Pyramidal Neurons ◽  
Receptor Blocker ◽  
Spine Density ◽  
Adult Rats ◽  
Electrophysiological Properties ◽  
Ca1 Pyramidal Neurons ◽  
Postsynaptic Potential

Previous studies have shown that GABA can have a depolarizing and excitatory action through GABAA receptors in mature CNS neurons in vitro. However, it remains unknown whether this occurs under physiological conditions. In this study, using intracellular recording and staining in vivo technique, we show a late depolarizing postsynaptic potential (L-PSP) in CA1 pyramidal neurons of adult Wistar rats under halothane anesthesia. This L-PSP was elicited in ∼70% of the recorded neurons on stimulation of the Schaffer collaterals or the contralateral commissural path. The size of L-PSP was linearly correlated to the decay time constant but not the rising slope of the initial excitatory PSP (EPSP). Intravenous administration of the N-methyl-d-aspartate (NMDA) receptor blocker MK-801 and the GABAA receptor blocker picrotoxin significantly reduced the size of the L-PSP. The spine density and apical dendritic branching length of the neurons that displayed L-PSPs was significantly greater than those that do not. These results indicate that NMDA receptor and GABAA receptor-mediated depolarizing postsynaptic potentials can be revealed in CA1 pyramidal neurons of adult rats in vivo, supporting the physiological relevance of GABAA-mediated depolarization in normal neuronal information processing. The difference in electrophysiological properties and morphological features between neurons that display the L-PSP and the other neurons suggest that they might represent two different subtypes of CA1 pyramidal neurons.

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 High levels of 27-hydroxycholesterol results in synaptic plasticity alterations in the hippocampus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Raul Loera-Valencia ◽  
Erika Vazquez-Juarez ◽  
Alberto Muñoz ◽  
Gorka Gerenu ◽  
Marta Gómez-Galán ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Memory Function ◽  
Long Term Potentiation ◽  
Synaptic Function ◽  
Cholesterol Homeostasis ◽  
Stratum Radiatum ◽  
Actin Binding ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Term Potentiation

AbstractAlterations in brain cholesterol homeostasis in midlife are correlated with a higher risk of developing Alzheimer’s disease (AD). However, global cholesterol-lowering therapies have yielded mixed results when it comes to slowing down or preventing cognitive decline in AD. We used the transgenic mouse model Cyp27Tg, with systemically high levels of 27-hydroxycholesterol (27-OH) to examine long-term potentiation (LTP) in the hippocampal CA1 region, combined with dendritic spine reconstruction of CA1 pyramidal neurons to detect morphological and functional synaptic alterations induced by 27-OH high levels. Our results show that elevated 27-OH levels lead to enhanced LTP in the Schaffer collateral-CA1 synapses. This increase is correlated with abnormally large dendritic spines in the stratum radiatum. Using immunohistochemistry for synaptopodin (actin-binding protein involved in the recruitment of the spine apparatus), we found a significantly higher density of synaptopodin-positive puncta in CA1 in Cyp27Tg mice. We hypothesize that high 27-OH levels alter synaptic potentiation and could lead to dysfunction of fine-tuned processing of information in hippocampal circuits resulting in cognitive impairment. We suggest that these alterations could be detrimental for synaptic function and cognition later in life, representing a potential mechanism by which hypercholesterolemia could lead to alterations in memory function in neurodegenerative diseases.

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