scholarly journals Distinct Role of Long 3′ UTR BDNF mRNA in Spine Morphology and Synaptic Plasticity in Hippocampal Neurons

Cell ◽  
2008 ◽  
Vol 134 (1) ◽  
pp. 175-187 ◽  
Author(s):  
Juan Ji An ◽  
Kusumika Gharami ◽  
Guey-Ying Liao ◽  
Newton H. Woo ◽  
Anthony G. Lau ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Hippocampal Neurons ◽  
Bdnf Mrna ◽  
Spine Morphology ◽  
Distinct Role

scholarly journals TNF-alpha contributes to spinal cord synaptic plasticity and inflammatory pain: Distinct role of TNF receptor subtypes 1 and 2

Pain ◽  
2011 ◽  
Vol 152 (2) ◽  
pp. 419-427 ◽  
Author(s):  
Ling Zhang ◽  
Temugin Berta ◽  
Zhen-Zhong Xu ◽  
Tong Liu ◽  
Jong Yeon Park ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Synaptic Plasticity ◽  
Inflammatory Pain ◽  
Tnf Alpha ◽  
Receptor Subtypes ◽  
Tnf Receptor ◽  
Distinct Role

scholarly journals Dendritic spine morphology and memory formation depend on postsynaptic Caskin proteins

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Norbert Bencsik ◽  
Szilvia Pusztai ◽  
Sándor Borbély ◽  
Anna Fekete ◽  
Metta Dülk ◽  
...  
Keyword(s):  
Dendritic Spine ◽  
Knockout Mice ◽  
Hippocampal Neurons ◽  
Pain Perception ◽  
Hippocampal Slices ◽  
Scaffold Proteins ◽  
Double Knockout ◽  
Learning Abilities ◽  
Spine Morphology

AbstractCASK-interactive proteins, Caskin1 and Caskin2, are multidomain neuronal scaffold proteins. Recent data from Caskin1 knockout animals indicated only a mild role of Caskin1 in anxiety and pain perception. In this work, we show that deletion of both Caskins leads to severe deficits in novelty recognition and spatial memory. Ultrastructural analyses revealed a reduction in synaptic profiles and dendritic spine areas of CA1 hippocampal pyramidal neurons of double knockout mice. Loss of Caskin proteins impaired LTP induction in hippocampal slices, while miniature EPSCs in dissociated hippocampal cultures appeared to be unaffected. In cultured Caskin knockout hippocampal neurons, overexpressed Caskin1 was enriched in dendritic spine heads and increased the amount of mushroom-shaped dendritic spines. Chemically induced LTP (cLTP) mediated enlargement of spine heads was augmented in the knockout mice and was not influenced by Caskin1. Immunocytochemistry and immunoprecipitation confirmed that Shank2, a master scaffold of the postsynaptic density, and Caskin1 co-localized within the same complex. Phosphorylation of AMPA receptors was specifically altered by Caskin deficiency and was not elevated by cLTP treatment further. Taken together, our results prove a previously unnoticed postsynaptic role of Caskin scaffold proteins and indicate that Caskins influence learning abilities via regulating spine morphology and AMPA receptor localisation.

scholarly journals Neuronal megalin mediates synaptic plasticity—a novel mechanism underlying intellectual disabilities in megalin gene pathologies

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
João R Gomes ◽  
Andrea Lobo ◽  
Renata Nogueira ◽  
Ana F Terceiro ◽  
Susete Costelha ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Intellectual Disabilities ◽  
Learning And Memory ◽  
Neuronal Activity ◽  
Hippocampal Neurons ◽  
Molecular Mechanisms ◽  
Genetic Disorder ◽  
Cell Surface Receptor ◽  
Neuronal Cultures

Abstract Donnai-Barrow syndrome, a genetic disorder associated to LRP2 (low-density lipoprotein receptor 2/megalin) mutations, is characterized by unexplained neurological symptoms and intellectual deficits. Megalin is a multifunctional endocytic clearance cell-surface receptor, mostly described in epithelial cells. This receptor is also expressed in the CNS, mainly in neurons, being involved in neurite outgrowth and neuroprotective mechanisms. Yet, the mechanisms involved in the regulation of megalin in the CNS are poorly understood. Using transthyretin knockout mice, a megalin ligand, we found that transthyretin positively regulates neuronal megalin levels in different CNS areas, particularly in the hippocampus. Transthyretin is even able to rescue megalin downregulation in transthyretin knockout hippocampal neuronal cultures, in a positive feedback mechanism via megalin. Importantly, transthyretin activates a regulated intracellular proteolysis mechanism of neuronal megalin, producing an intracellular domain, which is translocated to the nucleus, unveiling megalin C-terminal as a potential transcription factor, able to regulate gene expression. We unveil that neuronal megalin reduction affects physiological neuronal activity, leading to decreased neurite number, length and branching, and increasing neuronal susceptibility to a toxic insult. Finally, we unravel a new unexpected role of megalin in synaptic plasticity, by promoting the formation and maturation of dendritic spines, and contributing for the establishment of active synapses, both in in vitro and in vivo hippocampal neurons. Moreover, these structural and synaptic roles of megalin impact on learning and memory mechanisms, since megalin heterozygous mice show hippocampal-related memory and learning deficits in several behaviour tests. Altogether, we unveil a complete novel role of megalin in the physiological neuronal activity, mainly in synaptic plasticity with impact in learning and memory. Importantly, we contribute to disclose the molecular mechanisms underlying the cognitive and intellectual disabilities related to megalin gene pathologies.

scholarly journals Overexpression of Tropomyosin Isoform Tpm3.1 Does Not Alter Synaptic Function in Hippocampal Neurons

2021 ◽  
Vol 22 (17) ◽  
pp. 9303
Author(s):  
Chanchanok Chaichim ◽  
Tamara Tomanic ◽  
Holly Stefen ◽  
Esmeralda Paric ◽  
Lucy Gamaroff ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Hippocampal Neurons ◽  
Brain Slices ◽  
Structure And Function ◽  
Spine Morphology ◽  
Dendritic Spine Morphology ◽  
And Function ◽  
Cultured Hippocampal Neurons

Tropomyosin (Tpm) has been regarded as the master regulator of actin dynamics. Tpms regulate the binding of the various proteins involved in restructuring actin. The actin cytoskeleton is the predominant cytoskeletal structure in dendritic spines. Its regulation is critical for spine formation and long-term activity-dependent changes in synaptic strength. The Tpm isoform Tpm3.1 is enriched in dendritic spines, but its role in regulating the synapse structure and function is not known. To determine the role of Tpm3.1, we studied the synapse structure and function of cultured hippocampal neurons from transgenic mice overexpressing Tpm3.1. We recorded hippocampal field excitatory postsynaptic potentials (fEPSPs) from brain slices to examine if Tpm3.1 overexpression alters long-term synaptic plasticity. Tpm3.1-overexpressing cultured neurons did not show a significantly altered dendritic spine morphology or synaptic activity. Similarly, we did not observe altered synaptic transmission or plasticity in brain slices. Furthermore, expression of Tpm3.1 at the postsynaptic compartment does not increase the local F-actin levels. The results suggest that although Tpm3.1 localises to dendritic spines in cultured hippocampal neurons, it does not have any apparent impact on dendritic spine morphology or function. This is contrary to the functional role of Tpm3.1 previously observed at the tip of growing neurites, where it increases the F-actin levels and impacts growth cone dynamics.

The role of actin in the regulation of dendritic spine morphology and bidirectional synaptic plasticity

Neuroreport ◽  
2004 ◽  
Vol 15 (5) ◽  
pp. 829-832 ◽  
Author(s):  
Yucui Chen ◽  
Jennifer Bourne ◽  
Vincent A. Pieribone ◽  
Reiko Maki Fitzsimonds
Keyword(s):  
Synaptic Plasticity ◽  
Dendritic Spine ◽  
Spine Morphology ◽  
Dendritic Spine Morphology

scholarly journals Protective Role of NMDAR for Microwave-Induced Synaptic Plasticity Injuries in Primary Hippocampal Neurons

2018 ◽  
Vol 51 (1) ◽  
pp. 97-112 ◽  
Author(s):  
Hui Wang ◽  
Shengzhi Tan ◽  
Li Zhao ◽  
Ji Dong ◽  
Binwei Yao ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Patch Clamp ◽  
Western Blot ◽  
Microwave Radiation ◽  
Hippocampal Neurons ◽  
Microwave Exposure ◽  
Whole Cell Patch Clamp ◽  
Primary Hippocampal Neurons ◽  
Nmdar Subunits

Background/Aims: The N-methyl-D-aspartic acid receptor (NMDAR) has been extensively studied for its important roles in synaptic plasticity and learning and memory. However, the effects of microwave radiation on the subunit composition and activity of NMDARs and the relationship between NMDARs and microwave-induced synaptic plasticity have not been thoroughly elucidated to date. Materials: In our study, primary hippocampal neurons were used to evaluate the effects of microwave radiation on synaptic plasticity. Structural changes were observed by diolistic (Dil) labeling and scanning electron microscopy (SEM) observation. Functional synaptic plasticity was reflected by the NMDAR currents, which were detected by whole cell patch clamp. We also detected the expression of NMDAR subunits by real-time PCR and Western blot analysis. To clarify the effects of microwave radiation on NMDAR-induced synaptic plasticity, suitable agonists or inhibitors were added to confirm the role of NMDARs on microwave-induced synaptic plasticity. Dil labeling, SEM observation, whole cell patch clamp, real-time PCR and Western blot analysis were used to evaluate changes in synaptic plasticity after treatment with agonists or inhibitors. Results: Our results found that microwave exposure impaired neurite development and decreased mRNA and protein levels and the current density of NMDARs. Due to the decreased expression of NMDAR subunits after microwave exposure, the selective agonist NMDA was added to identify the role of NMDARs on microwave-induced synaptic plasticity injuries. After adding the agonist, the expression of NMDAR subunits recovered to the normal levels. In addition, the microwave-induced structural and functional synaptic plasticity injuries recovered, including the number and length of neurites, the connections between neurons, and the NMDAR current. Conclusion: Microwave radiation caused neuronal synaptic plasticity injuries in primary hippocampal neurons, and NMDARs played protective roles on the damage process.

scholarly journals Hepatocyte Growth Factor in Synaptic Plasticity and Alzheimer's Disease

2010 ◽  
Vol 10 ◽  
pp. 457-461 ◽  
Author(s):  
Shiv K. Sharma
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synaptic Plasticity ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Receptor Tyrosine Kinase ◽  
Hippocampal Neurons ◽  
Different Types ◽  
Hepatocyte Growth

The hepatocyte growth factor (HGF) was initially identified as a protein that promoted growth of hepatocytes. It regulates proliferation and survival of different types of cells. HGF signaling, which is initiated by its binding to a receptor tyrosine kinase, plays critical roles during development. HGF and its receptor are also present in brain cells. This review describes the role of HGF in hippocampal neurons, synaptic plasticity, and the memory impairment condition, Alzheimer's disease.

scholarly journals APPsα rescues impaired Ca2+ homeostasis in APP- and APLP2-deficient hippocampal neurons

2021 ◽  
Vol 118 (26) ◽  
pp. e2011506118
Author(s):  
Susann Ludewig ◽  
Ulrike Herrmann ◽  
Kristin Michaelsen-Preusse ◽  
Kristin Metzdorf ◽  
Jennifer Just ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Hippocampal Neurons ◽  
Therapeutic Potential ◽  
Amyloid Β ◽  
Physiological Role ◽  
In Vivo Studies ◽  
Associated Proteins

Alterations in Ca2+ homeostasis have been reported in several in vitro and in vivo studies using mice expressing the Alzheimer’s disease–associated transgenes, presenilin and the amyloid precursor protein (APP). While intense research focused on amyloid-β–mediated functions on neuronal Ca2+ handling, the physiological role of APP and its close homolog APLP2 is still not fully clarified. We now elucidate a mechanism to show how APP and its homolog APLP2 control neuronal Ca2+ handling and identify especially the ectodomain APPsα as an essential regulator of Ca2+ homeostasis. Importantly, we demonstrate that the loss of APP and APLP2, but not APLP2 alone, impairs Ca2+ handling, the refill of the endoplasmic reticulum Ca2+ stores, and synaptic plasticity due to altered function and expression of the SERCA-ATPase and expression of store-operated Ca2+ channel–associated proteins Stim1 and Stim2. Long-term AAV-mediated expression of APPsα, but not acute application of the recombinant protein, restored physiological Ca2+ homeostasis and synaptic plasticity in APP/APLP2 cDKO cultures. Overall, our analysis reveals an essential role of the APP family and especially of the ectodomain APPsα in Ca2+ homeostasis, thereby highlighting its therapeutic potential.

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