scholarly journals Rescue of Synaptic Failure and Alleviation of Learning and Memory Impairments in a Trisomic Mouse Model of Down Syndrome

2011 ◽  
Vol 70 (12) ◽  
pp. 1070-1079 ◽  
Author(s):  
Julie Blanchard ◽  
Silvia Bolognin ◽  
Muhammad Omar Chohan ◽  
Ausma Rabe ◽  
Khalid Iqbal ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Mouse Model ◽  
Learning And Memory ◽  
Memory Impairments ◽  
Synaptic Failure

scholarly journals Early Hippocampal Sharp-Wave Ripple Deficits Predict Later Learning and Memory Impairments in an Alzheimer’s Disease Mouse Model

Cell Reports ◽  
2019 ◽  
Vol 29 (8) ◽  
pp. 2123-2133.e4 ◽  
Author(s):  
Emily A. Jones ◽  
Anna K. Gillespie ◽  
Seo Yeon Yoon ◽  
Loren M. Frank ◽  
Yadong Huang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Learning And Memory ◽  
Memory Impairments ◽  
Sharp Wave

scholarly journals Forebrain Shh overexpression improves cognitive function and locomotor hyperactivity in an aneuploid mouse model of Down syndrome and its euploid littermates

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Feng J. Gao ◽  
Donna Klinedinst ◽  
Fabian-Xosé Fernandez ◽  
Bei Cheng ◽  
Alena Savonenko ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Cognitive Function ◽  
Mouse Model ◽  
Learning And Memory ◽  
Perinatal Period ◽  
Cerebellar Hypoplasia ◽  
Shh Signaling ◽  
Site Specific ◽  
Locomotor Hyperactivity

AbstractDown syndrome (DS) is the leading genetic cause of intellectual disability and causes early-onset dementia and cerebellar hypoplasia. The prevalence of attention deficit hyperactivity disorder is elevated in children with DS. The aneuploid DS mouse model “Ts65Dn” shows prominent brain phenotypes, including learning and memory deficits, cerebellar hypoplasia, and locomotor hyperactivity. Previous studies indicate that impaired Sonic hedgehog (Shh) signaling contributes to neurological phenotypes associated with DS and neurodegenerative diseases. However, because of a lack of working inducible Shh knock-in mice, brain region-specific Shh overexpression and its effects on cognitive function have not been studied in vivo. Here, with Gli1-LacZ reporter mice, we demonstrated that Ts65Dn had reduced levels of Gli1, a sensitive readout of Shh signaling, in both hippocampus and cerebellum at postnatal day 6. Through site-specific transgenesis, we generated an inducible human Shh knock-in mouse, TRE-bi-hShh-Zsgreen1 (TRE-hShh), simultaneously expressing dually-lipidated Shh-Np and Zsgreen1 marker in the presence of transactivator (tTA). Double transgenic mice “Camk2a-tTA;TRE-hShh” and “Pcp2-tTA;TRE-hShh” induced Shh overexpression and activated Shh signaling in a forebrain and cerebellum, respectively, specific manner from the perinatal period. Camk2a-tTA;TRE-hShh normalized locomotor hyperactivity and improved learning and memory in 3-month-old Ts65Dn, mitigated early-onset severe cognitive impairment in 7-month-old Ts65Dn, and enhanced spatial cognition in euploid mice. Camk2a-tTA;TRE-hShh cohort maintained until 600days old showed that chronic overexpression of Shh in forebrain from the perinatal period had no effect on longevity of euploid or Ts65Dn. Pcp2-tTA;TRE-hShh did not affect cognition but mitigated the phenotype of cerebellar hypoplasia in Ts65Dn. Our study provides the first in vivo evidence that Shh overexpression from the perinatal period protects DS brain integrity and enhances learning and memory in normal mice, indicating the broad therapeutic potential of Shh ligand for other neurological conditions. Moreover, the first inducible hShh site-specific knock-in mouse could be widely used for spatiotemporal Shh signaling regulation.

scholarly journals Learning and memory impairments in a neuroendocrine mouse model of anxiety/depression

2014 ◽  
Vol 8 ◽  
Author(s):  
Flavie Darcet ◽  
Indira Mendez-David ◽  
Laurent Tritschler ◽  
Alain M. Gardier ◽  
Jean-Philippe Guilloux ◽  
...  
Keyword(s):  
Mouse Model ◽  
Learning And Memory ◽  
Memory Impairments ◽  
Anxiety Depression

scholarly journals Adult-Onset Fluoxetine Treatment Does Not Improve Behavioral Impairments and May Have Adverse Effects on the Ts65Dn Mouse Model of Down Syndrome

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Markus Heinen ◽  
Moritz M. Hettich ◽  
Devon P. Ryan ◽  
Susanne Schnell ◽  
Katharina Paesler ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Mouse Model ◽  
Chromosome 21 ◽  
Adult Onset ◽  
Ts65dn Mouse ◽  
Receptor Antagonists ◽  
Memory Impairments ◽  
Severe Intellectual Disability ◽  
Fluoxetine Treatment ◽  
Behavioral Impairments

Down syndrome is caused by triplication of chromosome 21 and is associated with neurocognitive phenotypes ranging from severe intellectual disability to various patterns of more selective neuropsychological deficits, including memory impairments. In the Ts65Dn mouse model of Down syndrome, excessive GABAergic neurotransmission results in local over-inhibition of hippocampal circuits, which dampens hippocampal synaptic plasticity and contributes to cognitive impairments. Treatments with several GABAAreceptor antagonists result in increased plasticity and improved memory deficits in Ts65Dn mice. These GABAAreceptor antagonists are, however, not suitable for clinical applications. The selective serotonin reuptake inhibitor fluoxetine, in contrast, is a widely prescribed antidepressant that can also enhance plasticity in the adult rodent brain by lowering GABAergic inhibition. For these reasons, we wondered if an adult-onset 4-week oral fluoxetine treatment restores spatial learning and memory impairments in Ts65Dn mice. Fluoxetine did not measurably improve behavioral impairments of Ts65Dn mice. On the contrary, we observed seizures and mortality in fluoxetine-treated Ts65Dn mice, raising the possibility of a drug × genotype interaction with respect to these adverse treatment outcomes. Future studies should re-address this in larger animal cohorts and determine if fluoxetine treatment is associated with adverse treatment effects in individuals with Down syndrome.

P2-450: Hemizygous deletion of synaptojanin1 ameliorates learning and memory impairments in a mouse model of Alzheimer's disease

2010 ◽  
Vol 6 ◽  
pp. e8-e8
Author(s):  
Laura Beth J. McIntire ◽  
Diego Berman ◽  
Jennifer Myaeng ◽  
Agniezka Staniszewski ◽  
Ottavio Arancio ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Learning And Memory ◽  
Memory Impairments ◽  
Hemizygous Deletion ◽  
Model Of Alzheimer’S Disease

scholarly journals Aerobic exercise and a BDNF-mimetic therapy rescue learning and memory in a mouse model of Down syndrome

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Martina Parrini ◽  
Diego Ghezzi ◽  
Gabriele Deidda ◽  
Lucian Medrihan ◽  
Enrico Castroflorio ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Mouse Model ◽  
Aerobic Exercise ◽  
Learning And Memory

Probiotic supplementation attenuates hippocampus injury and spatial learning and memory impairments in a cerebral hypoperfusion mouse model

2019 ◽  
Vol 46 (5) ◽  
pp. 4985-4995 ◽  
Author(s):  
Hamideh Rahmati ◽  
Shahein Momenabadi ◽  
Abbas Ali Vafaei ◽  
Ahmad Reza Bandegi ◽  
Zohreh Mazaheri ◽  
...  
Keyword(s):  
Mouse Model ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Cerebral Hypoperfusion ◽  
Spatial Learning And Memory ◽  
Probiotic Supplementation ◽  
Memory Impairments
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