scholarly journals The space where aging acts: focus on the GABAergic synapse

Aging Cell ◽  
2017 ◽  
Vol 16 (4) ◽  
pp. 634-643 ◽  
Author(s):  
Aleksandra Rozycka ◽  
Monika Liguz-Lecznar
Keyword(s):  
Gabaergic Synapse

scholarly journals Activation of Apoptosis in a βB1-CTGF Transgenic Mouse Model

2021 ◽  
Vol 22 (4) ◽  
pp. 1997
Author(s):  
Maximilian Weiss ◽  
Sabrina Reinehr ◽  
Ana M. Mueller-Buehl ◽  
Johanna D. Doerner ◽  
Rudolf Fuchshofer ◽  
...  
Keyword(s):  
Open Angle Glaucoma ◽  
Bipolar Cells ◽  
Nerve Degeneration ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Pcr Analysis ◽  
Progression Rate ◽  
Suitable Model ◽  
Mrna Levels ◽  
Gabaergic Synapse ◽  
Slow Progression

To reveal the pathomechanisms of glaucoma, a common cause of blindness, suitable animal models are needed. As previously shown, retinal ganglion cell and optic nerve degeneration occur in βB1-CTGF mice. Here, we aimed to determine possible apoptotic mechanisms and degeneration of different retinal cells. Hence, retinae were processed for immunohistology (n = 5–9/group) and quantitative real-time PCR analysis (n = 5–7/group) in 5- and 10-week-old βB1-CTGF and wildtype controls. We noted significantly more cleaved caspase 3+ cells in βB1-CTGF retinae at 5 (p = 0.005) and 10 weeks (p = 0.02), and a significant upregulation of Casp3 and Bax/Bcl2 mRNA levels (p < 0.05). Furthermore, more terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL+) cells were detected in transgenic mice at 5 (p = 0.03) and 10 weeks (p = 0.02). Neurofilament H staining (p = 0.01) as well as Nefh (p = 0.02) and Tubb3 (p = 0.009) mRNA levels were significantly decreased at 10 weeks. GABAergic synapse intensity was lower at 5 weeks, while no alterations were noted at 10 weeks. The glutamatergic synapse intensity was decreased at 5 (p = 0.007) and 10 weeks (p = 0.01). No changes were observed for bipolar cells, photoreceptors, and macroglia. We conclude that apoptotic processes and synapse loss precede neuronal death in this model. This slow progression rate makes the βB1-CTGF mice a suitable model to study primary open-angle glaucoma.

Receptive field of the retinal bipolar cell: a pharmacological study in the tiger salamander

1996 ◽  
Vol 76 (3) ◽  
pp. 2005-2019 ◽  
Author(s):  
W. A. Hare ◽  
W. G. Owen
Keyword(s):  
Receptive Field ◽  
Gaba Receptors ◽  
Bipolar Cell ◽  
Horizontal Cell ◽  
Pharmacological Study ◽  
Bipolar Cells ◽  
Horizontal Cells ◽  
Gaba Uptake ◽  
Gamma Aminobutyric Acid ◽  
Gabaergic Synapse

1. It is widely believed that signals contributing to the receptive field surrounds of retinal bipolar cells pass from horizontal cells to bipolar cells via GABAergic synapses. To test this notion, we applied gamma-aminobutyric acid (GABA) agonists and antagonists to isolated, perfused retinas of the salamander Ambystoma tigrinum while recording intracellularly from bipolar cells, horizontal cells, and photoreceptors. 2. As we previously reported, administration of the GABA analogue D-aminovaleric acid in concert with picrotoxin did not block horizontal cell responses or the center responses of bipolar cells but blocked the surround responses of both on-center and off-center bipolar cells. 3. Surround responses were not blocked by the GABA, antagonists picrotoxin or bicuculline, the GABAB agonist baclofen or the GABAB antagonist phaclofen, and the GABAC antagonists picrotoxin or cis-4-aminocrotonic acid. Combinations of these drugs were similarly ineffective. 4. GABA itself activated a powerful GABA uptake mechanism in horizontal cells for which nipecotic acid is a competitive agonist. It also activated, both in horizontal cells and bipolar cells, large GABAA conductances that shunted light responses but that could be blocked by picrotoxin or bicuculline. 5. GABA, administered together with picrotoxin to block the shunting effect of GABAA activation, did not eliminate bipolar cell surround responses at concentrations sufficient to saturate the known types of GABA receptors. 6. Surround responses were not blocked by glycine or its antagonist strychnine, or by combinations of drugs designed to eliminate GABAergic and glycinergic pathways simultaneously. 7. Although we cannot fully discount the involvement of a novel GABAergic synapse, the simplest explanation of our findings is that the primary pathway mediating the bipolar cell's surround is neither GABAergic nor glycinergic.

scholarly journals Regulation of GABAergic synapse formation and plasticity by GSK3β-dependent phosphorylation of gephyrin

2010 ◽  
Vol 108 (1) ◽  
pp. 379-384 ◽  
Author(s):  
Shiva K. Tyagarajan ◽  
Himanish Ghosh ◽  
Gonzalo E. Yévenes ◽  
Irina Nikonenko ◽  
Claire Ebeling ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Hippocampal Neurons ◽  
Glycogen Synthase ◽  
Phosphorylation Site ◽  
Scaffolding Protein ◽  
Scaffolding Proteins ◽  
Gabaergic Synapse ◽  
Gabaergic Synapses

Postsynaptic scaffolding proteins ensure efficient neurotransmission by anchoring receptors and signaling molecules in synapse-specific subcellular domains. In turn, posttranslational modifications of scaffolding proteins contribute to synaptic plasticity by remodeling the postsynaptic apparatus. Though these mechanisms are operant in glutamatergic synapses, little is known about regulation of GABAergic synapses, which mediate inhibitory transmission in the CNS. Here, we focused on gephyrin, the main scaffolding protein of GABAergic synapses. We identify a unique phosphorylation site in gephyrin, Ser270, targeted by glycogen synthase kinase 3β (GSK3β) to modulate GABAergic transmission. Abolishing Ser270 phosphorylation increased the density of gephyrin clusters and the frequency of miniature GABAergic postsynaptic currents in cultured hippocampal neurons. Enhanced, phosphorylation-dependent gephyrin clustering was also induced in vitro and in vivo with lithium chloride. Lithium is a GSK3β inhibitor used therapeutically as mood-stabilizing drug, which underscores the relevance of this posttranslational modification for synaptic plasticity. Conversely, we show that gephyrin availability for postsynaptic clustering is limited by Ca2+-dependent gephyrin cleavage by the cysteine protease calpain-1. Together, these findings identify gephyrin as synaptogenic molecule regulating GABAergic synaptic plasticity, likely contributing to the therapeutic action of lithium.

scholarly journals Sema4D localizes to synapses and regulates GABAergic synapse development as a membrane-bound molecule in the mammalian hippocampus

2013 ◽  
Vol 57 ◽  
pp. 23-32 ◽  
Author(s):  
Aram J. Raissi ◽  
Emily K. Staudenmaier ◽  
Serena David ◽  
Linda Hu ◽  
Suzanne Paradis
Keyword(s):  
Synapse Development ◽  
Gabaergic Synapse ◽  
Membrane Bound

scholarly journals Loss of IQSEC3 Disrupts GABAergic Synapse Maintenance and Decreases Somatostatin Expression in the Hippocampus

Cell Reports ◽  
2020 ◽  
Vol 30 (6) ◽  
pp. 1995-2005.e5 ◽  
Author(s):  
Seungjoon Kim ◽  
Hyeonho Kim ◽  
Dongseok Park ◽  
Jinhu Kim ◽  
Joohyeon Hong ◽  
...  
Keyword(s):  
Gabaergic Synapse ◽  
Synapse Maintenance ◽  
Somatostatin Expression

Sympathoinhibition evoked from caudal midline medulla is mediated by GABA receptors in rostral VLM

1998 ◽  
Vol 274 (2) ◽  
pp. R318-R323 ◽  
Author(s):  
Matthew J. Coleman ◽  
Roger A. L. Dampney
Keyword(s):  
Sympathetic Nerve ◽  
Gaba Receptors ◽  
Sympathetic Nerve Activity ◽  
Background Level ◽  
Ventrolateral Medulla ◽  
Nerve Activity ◽  
Gabaergic Synapse ◽  
Renal Sympathetic Nerve Activity ◽  
Renal Sympathetic Nerve ◽  
Renal Sympathetic

The present study was performed to determine whether the powerful depressor and sympathoinhibitory response that can be evoked from neurons in the caudal midline medulla is mediated by γ-aminobutyric acidergic (GABAergic) inhibition of sympathoexcitatory neurons in the rostral part of the ventrolateral medulla (VLM). In anesthetized barointact and barodenervated rabbits, bilateral microinjections of bicuculline into sympathoexcitatory sites in the rostral VLM resulted in a sustained increase in renal sympathetic nerve activity and abolished or reversed the depressor and sympathoinhibitory response evoked by glutamate microinjection into the caudal midline medulla. By contrast, the sympathoinhibitory response evoked from the caudal midline medulla persisted when the background level of renal sympathetic nerve activity was reflexly raised by baroreceptor unloading. The results indicate that 1) the depressor and sympathoinhibitory response evoked by stimulation of neurons in the caudal midline medulla is mediated by a GABAergic synapse in the rostral VLM and 2) there are also sympathoexcitatory neurons in the caudal midline medulla whose presence is revealed by blockade of the more powerful sympathoinhibitory response.

scholarly journals Functional Hallmarks of GABAergic Synapse Maturation and the Diverse Roles of Neurotrophins

2011 ◽  
Vol 5 ◽  
Author(s):  
Rosemarie Grantyn ◽  
Christian Henneberger ◽  
René Jüttner ◽  
Jochen C. Meier ◽  
Sergei Kirischuk
Keyword(s):  
Gabaergic Synapse ◽  
Synapse Maturation
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