scholarly journals Overexpression of novel candidate gene ameliorates dendritic simplification in hippocampal neurons from APP/PS1 mouse model of AD

2020 ◽  
Vol 16 (S2) ◽  
Author(s):  
Aditi Verma ◽  
Barathan Gnanabharathi ◽  
Sunny Kumar ◽  
Ruturaj Gowaikar ◽  
Arathy Ramachandran ◽  
...  
Keyword(s):  
Mouse Model ◽  
Candidate Gene ◽  
Hippocampal Neurons ◽  
Dendritic Simplification

Abnormal responses of hippocampal neurons to auditory paired-click stimuli in a neurodevelopmental mouse-model of schizophrena

2010 ◽  
Vol 68 ◽  
pp. e201
Author(s):  
Masahiro Okamoto ◽  
Eiichi Jodo ◽  
Tadahiro Katayama ◽  
Yoshiaki Suzuki ◽  
Ken-Yo Hoshino ◽  
...  
Keyword(s):  
Mouse Model ◽  
Hippocampal Neurons

Ts65Dn, a Mouse Model of Down Syndrome, Exhibits Increased GABAB-Induced Potassium Current

2007 ◽  
Vol 97 (1) ◽  
pp. 892-900 ◽  
Author(s):  
Tyler K. Best ◽  
Richard J. Siarey ◽  
Zygmunt Galdzicki
Keyword(s):  
Down Syndrome ◽  
Mouse Model ◽  
Hippocampal Neurons ◽  
Single Channel ◽  
Extra Chromosome ◽  
Functional Expression ◽  
Chromosome 21 ◽  
Fluctuation Analysis ◽  
Response Curves ◽  
Girk Channel

Down syndrome (DS) is the most common nonheritable cause of mental retardation. DS is the result of the presence of an extra chromosome 21 and its phenotype may be a consequence of overexpressed genes from that chromosome. One such gene is Kcnj6/Girk2, which encodes the G-protein-coupled inward rectifying potassium channel subunit 2 (GIRK2). We have recently shown that the DS mouse model, Ts65Dn, overexpresses GIRK2 throughout the brain and in particular the hippocampus. Here we report that this overexpression leads to a significant increase (∼2-fold) in GABAB-mediated GIRK current in primary cultured hippocampal neurons. The dose response curves for peak and steady-state GIRK current density is significantly shifted left toward lower concentrations of baclofen in Ts65Dn neurons compared with diploid controls, consistent with increased functional expression of GIRK channels. Stationary fluctuation analysis of baclofen-induced GIRK current from Ts65Dn neurons indicated no significant change in single-channel conductance compared with diploid. However, significant increases in GIRK channel density was found in Ts65Dn neurons. In normalized baclofen-induced GIRK current and GIRK current kinetics no difference was found between diploid and Ts65Dn neurons, which suggests unimpaired mechanisms of interaction between GIRK channel and GABAB receptor. These results indicate that increased expression of GIRK2 containing channels have functional consequences that likely affect the balance between excitatory and inhibitory neuronal transmission.

scholarly journals P2-138: IDENTIFICATION OF SIPA1L1 AS A NOVEL CANDIDATE GENE MEDIATING PRECLINICAL WEIGHT LOSS IN A MOUSE MODEL OF ALZHEIMER'S DISEASE

2019 ◽  
Vol 15 ◽  
pp. P625-P625
Author(s):  
Catherine C. Kaczorowski ◽  
Amy R. Dunn ◽  
Sarah M. Neuner ◽  
Vivek Kumar ◽  
Kristen MS O'Connell
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Weight Loss ◽  
Mouse Model ◽  
Candidate Gene ◽  
Model Of Alzheimer’S Disease

scholarly journals The intellectual disability PAK3 R67C mutation impacts cognitive functions and adult hippocampal neurogenesis

2020 ◽  
Vol 29 (12) ◽  
pp. 1950-1968
Author(s):  
Charlotte Castillon ◽  
Laurine Gonzalez ◽  
Florence Domenichini ◽  
Sandrine Guyon ◽  
Kevin Da Silva ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Mouse Model ◽  
Spatial Memory ◽  
Adult Neurogenesis ◽  
Hippocampal Neurons ◽  
Memory Task ◽  
Clinical Signs ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Adult Born Neurons

Abstract The link between mutations associated with intellectual disability (ID) and the mechanisms underlying cognitive dysfunctions remains largely unknown. Here, we focused on PAK3, a serine/threonine kinase whose gene mutations cause X-linked ID. We generated a new mutant mouse model bearing the missense R67C mutation of the Pak3 gene (Pak3-R67C), known to cause moderate to severe ID in humans without other clinical signs and investigated hippocampal-dependent memory and adult hippocampal neurogenesis. Adult male Pak3-R67C mice exhibited selective impairments in long-term spatial memory and pattern separation function, suggestive of altered hippocampal neurogenesis. A delayed non-matching to place paradigm testing memory flexibility and proactive interference, reported here as being adult neurogenesis-dependent, revealed a hypersensitivity to high interference in Pak3-R67C mice. Analyzing adult hippocampal neurogenesis in Pak3-R67C mice reveals no alteration in the first steps of adult neurogenesis, but an accelerated death of a population of adult-born neurons during the critical period of 18–28 days after their birth. We then investigated the recruitment of hippocampal adult-born neurons after spatial memory recall. Post-recall activation of mature dentate granule cells in Pak3-R67C mice was unaffected, but a complete failure of activation of young DCX + newborn neurons was found, suggesting they were not recruited during the memory task. Decreased expression of the KCC2b chloride cotransporter and altered dendritic development indicate that young adult-born neurons are not fully functional in Pak3-R67C mice. We suggest that these defects in the dynamics and learning-associated recruitment of newborn hippocampal neurons may contribute to the selective cognitive deficits observed in this mouse model of ID.

scholarly journals Adenovirus-Mediated Transduction of Insulin-Like Growth Factor 1 Protects Hippocampal Neurons from the Toxicity of Aβ Oligomers and Prevents Memory Loss in an Alzheimer Mouse Model

2019 ◽  
Vol 57 (3) ◽  
pp. 1473-1483 ◽  
Author(s):  
Maria Clara Selles ◽  
Juliana T. S. Fortuna ◽  
Maria F. Zappa-Villar ◽  
Yasmin P. R. de Faria ◽  
Amanda S. Souza ◽  
...  
Keyword(s):  
Growth Factor ◽  
Mouse Model ◽  
Hippocampal Neurons ◽  
Memory Loss ◽  
Insulin Like Growth Factor ◽  
Aβ Oligomers

scholarly journals Neurodevelopmental wiring deficits in the Ts65Dn mouse model of Down syndrome

2019 ◽  
Author(s):  
Shruti Jain ◽  
Christina A. Watts ◽  
Wilson C.J. Chung ◽  
Kristy Welshhans
Keyword(s):  
Down Syndrome ◽  
Corpus Callosum ◽  
Mouse Model ◽  
Hippocampal Neurons ◽  
Anterior Commissure ◽  
Axon Growth ◽  
Chromosome 21 ◽  
Ts65dn Mouse ◽  
Hippocampal Commissure ◽  
Interhemispheric Connectivity

AbstractDown syndrome is the most common genetic cause of intellectual disability and occurs due to the trisomy of human chromosome 21. Adolescent and adult brains from humans with Down syndrome exhibit various neurological phenotypes including a reduction in the size of the corpus callosum, hippocampal commissure and anterior commissure. However, it is unclear when and how these interhemispheric connectivity defects arise. Using the Ts65Dn mouse model of Down syndrome, we examined interhemispheric connectivity in postnatal day 0 (P0) Ts65Dn mouse brains. We find that there is no change in the volume of the corpus callosum or anterior commissure in P0 Ts65Dn mice. However, the volume of the hippocampal commissure is significantly reduced in P0 Ts65Dn mice, and this may contribute to the impaired learning and memory phenotype of this disorder. Interhemispheric connectivity defects that arise during development may be due to disrupted axon growth. In line with this, we find that developing hippocampal neurons display reduced axon length in vitro, as compared to neurons from their euploid littermates. This study is the first to report the presence of defective interhemispheric connectivity at the time of birth in Ts65Dn mice, providing evidence that early therapeutic intervention may be an effective time window for the treatment of Down syndrome.

scholarly journals Anti-NMDAR encephalitis induced in mice by active immunization with a peptide from amino-terminal domain of the GluN1 subunit

2020 ◽  
Author(s):  
Yuewen Ding ◽  
Zheye Zhou ◽  
Jinyu Chen ◽  
Yu Peng ◽  
Haitao Wang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Hippocampal Neurons ◽  
Calcium Influx ◽  
Memory Loss ◽  
Long Term Potentiation ◽  
Active Immunization ◽  
Amino Terminal ◽  
Terminal Domain ◽  
Nmdar Encephalitis ◽  
Amino Terminal Domain

Abstract Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a recently discovered autoimmune syndrome associated with psychosis, dyskinesia, and seizures. However, the underlying mechanisms of this disease remain unclear, in part because of a lack of suitable animal models. This study describes a novel mouse model of anti-NMDAR encephalitis that was induced by active immunization against NMDARs using amino-terminal domain peptides. After 12 weeks of immunization, the mice showed significant behavioral disorders and memory loss. Furthermore, antibodies from the cerebrospinal fluid of immunized mice lowered the surface NMDAR cluster density in hippocampal neurons. Immunization also impaired long-term potentiation at Schaffer collateral–CA1 synapses and reduced NMDAR-induced calcium influx. This novel mouse model may allow further research into the pathogenesis of anti-NMDAR encephalitis and aid in the development of new therapies for this disease.

scholarly journals D-limonene Inhibits Pentylenetetrazole-Induced Seizure via Adenosine A2A Receptor Modulation on GABAergic Neuronal Activity

2020 ◽  
Vol 21 (23) ◽  
pp. 9277
Author(s):  
Sowoon Seo ◽  
Yunjeong Song ◽  
Sun Mi Gu ◽  
Hyun Kyu Min ◽  
Jin Tae Hong ◽  
...  
Keyword(s):  
Mouse Model ◽  
Hippocampal Neurons ◽  
Anticonvulsant Activity ◽  
High Performance ◽  
Gamma Aminobutyric Acid ◽  
Receptor Modulation ◽  
Ptz Kindling ◽  
Study Results ◽  
Adenosine A2a

Background: Epilepsy is a chronic neurological disorder characterized by the recurrence of seizures. One-third of patients with epilepsy may not respond to antiseizure drugs. Purpose: We aimed to examine whether D-limonene, a cyclic monoterpene, exhibited any antiseizure activity in the pentylenetetrazole (PTZ)-induced kindling mouse model and in vitro. Methods: PTZ kindling mouse model was established by administering PTZ (30 mg/kg) intraperitoneally to mice once every 48 h. We performed immunoblot blots, immunohistochemistry (IHC), and high-performance liquid chromatography (HPLC) analysis after the behavioral study. Results: An acute injection of PTZ (60 mg/kg) induced seizure in mice, while pretreatment with D-limonene inhibited PTZ-induced seizure. Repeated administration of PTZ (30 mg/kg) increased the seizure score gradually in mice, which was reduced in D-limonene (10 mg/kg)-pretreated group. In addition, D-limonene treatment increased glutamate decarboxylase-67 (GAD-67) expression in the hippocampus. Axonal sprouting of hippocampal neurons after kindling was inhibited by D-limonene pretreatment. Moreover, D-limonene reduced the expression levels of Neuronal PAS Domain Protein 4 (Npas4)-induced by PTZ. Furthermore, the adenosine A2A antagonist SCH58261 and ZM241385 inhibited anticonvulsant activity and gamma-aminobutyric acid (GABA)ergic neurotransmission-induced by D-limonene. Conclusion: These results suggest that D-limonene exhibits anticonvulsant activity through modulation of adenosine A2A receptors on GABAergic neuronal function.

Dexmedetomidine reduced isoflurane neurotoxicity by preventing cytoskeletal depolymerization via the BDNF/RhoA signal pathway

2021 ◽  
Author(s):  
Liang Chi ◽  
Xiaoyang Yao ◽  
Caixia Gao ◽  
Huansheng Dong ◽  
huanqi Liu
Keyword(s):  
Mouse Model ◽  
Hippocampal Neurons ◽  
Water Maze ◽  
Critical Period ◽  
Caspase 3 ◽  
Neuronal Damage ◽  
Neuroprotective Effect ◽  
Signal Pathway ◽  
Neurocognitive Deficits ◽  
Developing Neurons

Abstract Background Dexmedetomidine (Dex) has a significant neuroprotective effect in isoflurane-induced neurotoxicity during the critical period of synaptogenesis. However, the mechanisms by which Dex protects developing neurons are not clear. This research evaluated the protective effect of Dex against neuronal damage induced by isoflurane using a mouse model. Methods Neonatal Swiss mice at postnatal day 7 (PND7) were injected intraperitoneally with 15µg/kg, 20µg/kg, or 25µg/kg Dex, or normal saline, and then treated with 2% isoflurane for 2h. The results showed that 20µg/kg Dex could reduce isoflurane-induced neurocognitive deficits as assessed using the Morris water maze. The mechanisms by which Dex protected neurons were investigated using hippocampal neurons isolated from PND4-7 mice and exposed to 2% isoflurane (2h). Dex prevented cytoskeletal depolymerization that was induced by isoflurane. Results 15µg/ml Dex significantly reduced the percentage of apoptotic neurons. Dex reduced expression of activated caspase-3 in neurons compared to isoflurane only exposed mice. Using primary cell cultures from neonatal mouse hippocampi, we determined that dexmedetomidine could reverse isoflurane-induced RhoA (a small

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