Transgenic Rodent Models to Study Alpha-Synuclein Pathogenesis, with a Focus on Cognitive Deficits

2014 ◽  
pp. 303-330 ◽  
Author(s):  
Asa Hatami ◽  
Marie-Francoise Chesselet
Keyword(s):  
Cognitive Deficits ◽  
Alpha Synuclein ◽  
Rodent Models

scholarly journals Neuropsychiatric and Cognitive Deficits in Parkinson’s Disease and Their Modeling in Rodents

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 684
Author(s):  
Mélina Decourt ◽  
Haritz Jiménez-Urbieta ◽  
Marianne Benoit-Marand ◽  
Pierre-Olivier Fernagut
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Learning And Memory ◽  
Cognitive Deficits ◽  
Cognitive Disorders ◽  
Alpha Synuclein ◽  
Motor Deficits ◽  
Motor Symptoms ◽  
Rodent Models ◽  
Non Motor Symptoms

Parkinson’s disease (PD) is associated with a large burden of non-motor symptoms including olfactory and autonomic dysfunction, as well as neuropsychiatric (depression, anxiety, apathy) and cognitive disorders (executive dysfunctions, memory and learning impairments). Some of these non-motor symptoms may precede the onset of motor symptoms by several years, and they significantly worsen during the course of the disease. The lack of systematic improvement of these non-motor features by dopamine replacement therapy underlines their multifactorial origin, with an involvement of monoaminergic and cholinergic systems, as well as alpha-synuclein pathology in frontal and limbic cortical circuits. Here we describe mood and neuropsychiatric disorders in PD and review their occurrence in rodent models of PD. Altogether, toxin-based rodent models of PD indicate a significant but non-exclusive contribution of mesencephalic dopaminergic loss in anxiety, apathy, and depressive-like behaviors, as well as in learning and memory deficits. Gene-based models display significant deficits in learning and memory, as well as executive functions, highlighting the contribution of alpha-synuclein pathology to these non-motor deficits. Collectively, neuropsychiatric and cognitive deficits are recapitulated to some extent in rodent models, providing partial but nevertheless useful options to understand the pathophysiology of non-motor symptoms and develop therapeutic options for these debilitating symptoms of PD.

scholarly journals Characterization of Cognitive Deficits in Rats Overexpressing Human Alpha-Synuclein in the Ventral Tegmental Area and Medial Septum Using Recombinant Adeno-Associated Viral Vectors

PLoS ONE ◽  
2013 ◽  
Vol 8 (5) ◽  
pp. e64844 ◽  
Author(s):  
Hélène Hall ◽  
Michael Jewett ◽  
Natalie Landeck ◽  
Nathalie Nilsson ◽  
Ulrika Schagerlöf ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Cognitive Deficits ◽  
Viral Vectors ◽  
Medial Septum ◽  
Alpha Synuclein ◽  
Ventral Tegmental

scholarly journals Mouse Models of Cognitive Deficits Due to Alpha-Synuclein Pathology

2011 ◽  
Vol 1 (3) ◽  
pp. 217-227 ◽  
Author(s):  
Iddo Magen ◽  
Marie-Françoise Chesselet
Keyword(s):  
Mouse Models ◽  
Cognitive Deficits ◽  
Alpha Synuclein

Prenatal inflammation and risk for schizophrenia: A role for immune proteins in neurodevelopment

2018 ◽  
Vol 30 (3) ◽  
pp. 1157-1178 ◽  
Author(s):  
Dana M. Allswede ◽  
Tyrone D. Cannon
Keyword(s):  
Cognitive Deficits ◽  
Inflammatory Markers ◽  
Potential Role ◽  
Synapse Formation ◽  
Potential Candidate ◽  
Rodent Models ◽  
Cellular Mechanisms ◽  
Established Risk Factor ◽  
Prenatal Inflammation

AbstractPrenatal inflammation is an established risk factor for schizophrenia. However, the specific inflammatory pathways that mediate this association remain unclear. Potential candidate systems include inflammatory markers produced by microglia, such as cytokines and complement. Accumulating evidence suggests that these markers play a role in typical neurodevelopmental processes, such as synapse formation and interneuron migration. Rodent models demonstrate that altered marker levels during the prenatal period can cause lasting deficits in these systems, leading to cognitive deficits that resemble schizophrenia. This review assesses the potential role of prenatal cytokine and complement elevations on the etiology of schizophrenia. The current neurobiological understanding of the development of schizophrenia is reviewed to identify candidate cellular mechanisms that may be influenced by prenatal inflammation. We discuss the functions that cytokines and complement may play in prenatal neurodevelopment, review evidence that links exposure to these factors with risk for schizophrenia, and consider how these markers may interact with genetic vulnerabilities to influence the neurodevelopment of schizophrenia. We consider how prenatal inflammatory exposure may influence childhood and adolescent developmental risk trajectories for schizophrenia. Finally, we identify areas of further research needed to support the development of anti-inflammatory treatments to prevent the development of schizophrenia in at-risk neonates.

scholarly journals Social isolation increased ADAR1 expressions leading to cognitive deficits of mice

2016 ◽  
Author(s):  
Wei Chen ◽  
Dong An ◽  
Hong Xu ◽  
Xiaoxin Cheng ◽  
Shiwei Wang ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Frontal Cortex ◽  
Social Isolation ◽  
Cognitive Deficits ◽  
Close Relation ◽  
Object Location ◽  
Rodent Models ◽  
Isolation Stress ◽  
Protein Expressions ◽  
Social Isolation Stress

A lot of literature show that social isolation stress could be a key reason that leads to cognitive deficits for both humans and rodent models; however, the detailed mechanisms are still not clear completely. ADAR1 (Adenosine deaminase acting on RNA) is an enzyme involved in RNA editing that has a close relation to cognitive function. We hypothesize that social isolation stress may impact the expression of ADAR1, leading to cognitive deficits. To prove our hypothesis, we evaluated the cognition ability of the mice isolated for different durations (2, 4, and 8 weeks) using object recognition and object location tests; we also measured ADAR1 expressions in hippocampus and cortex using immunohistochemistry and western blot. Our study showed that social isolation stress significantly induced spatial and non-spatial cognition deficits. In addition, social isolation significantly increased both the immuno reactivity and protein expressions of ADAR1 in the hippocampus and frontal cortex. Furthermore, we found that adolescent re-socialization recovered not only the cognition deficits but also the increased ADAR1 protein expression in hippocampus and the increased number of ADAR1 positive cells in frontal cortex of the isolated mice. In conclusion, social isolation stress significantly increased ADAR1 expressions in the hippocampus and cortex, leading to cognitive deficits.

scholarly journals Social isolation increased ADAR1 expressions leading to cognitive deficits of mice

2016 ◽  
Author(s):  
Wei Chen ◽  
Dong An ◽  
Hong Xu ◽  
Xiaoxin Cheng ◽  
Shiwei Wang ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Frontal Cortex ◽  
Social Isolation ◽  
Cognitive Deficits ◽  
Close Relation ◽  
Object Location ◽  
Rodent Models ◽  
Isolation Stress ◽  
Protein Expressions ◽  
Social Isolation Stress

A lot of literature show that social isolation stress could be a key reason that leads to cognitive deficits for both humans and rodent models; however, the detailed mechanisms are still not clear completely. ADAR1 (Adenosine deaminase acting on RNA) is an enzyme involved in RNA editing that has a close relation to cognitive function. We hypothesize that social isolation stress may impact the expression of ADAR1, leading to cognitive deficits. To prove our hypothesis, we evaluated the cognition ability of the mice isolated for different durations (2, 4, and 8 weeks) using object recognition and object location tests; we also measured ADAR1 expressions in hippocampus and cortex using immunohistochemistry and western blot. Our study showed that social isolation stress significantly induced spatial and non-spatial cognition deficits. In addition, social isolation significantly increased both the immuno reactivity and protein expressions of ADAR1 in the hippocampus and frontal cortex. Furthermore, we found that adolescent re-socialization recovered not only the cognition deficits but also the increased ADAR1 protein expression in hippocampus and the increased number of ADAR1 positive cells in frontal cortex of the isolated mice. In conclusion, social isolation stress significantly increased ADAR1 expressions in the hippocampus and cortex, leading to cognitive deficits.

scholarly journals Cortical alpha-synuclein preformed fibrils do not affect interval timing in mice

2021 ◽  
Author(s):  
Qiang Zhang ◽  
Hisham A Abdelmotilib ◽  
Travis Larson ◽  
Cameron Keomanivong ◽  
Mackenzie Conlon ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Mouse Models ◽  
Medial Prefrontal Cortex ◽  
Interval Timing ◽  
Alpha Synuclein ◽  
Motor Dysfunction ◽  
Rodent Models ◽  
Adeno Associated Virus ◽  
Prefrontal Cortical ◽  
Lewy Body Pathology

One hallmark feature of Parkinsons disease (PD) is Lewy body pathology associated with misfolded alpha-synuclein. Previous studies have shown that striatal injection of alpha-synuclein preformed fibrils (PFF) can induce misfolding and aggregation of native alpha-synuclein in a prion-like manner, leading to cell death and motor dysfunction in mouse models. Here, we tested whether alpha-synuclein PFFs injected into the medial prefrontal cortex results in cognitive deficits in mouse models as measured by interval timing, which is reliably disrupted in PD patients and in rodent models. We injected human alpha-synuclein PFF or monomers in the medial prefrontal cortex pre-injected with adeno-associated virus (AAV) overexpressing human alpha-synuclein. Despite notable medial prefrontal cortical synucleinopathy, we did not observe consistent deficits in fixed-interval timing. These results suggest that cortical alpha-synuclein does not reliably disrupt interval timing in rodent models.

164: Are Gabab Receptors Involved in Gabapentin Inhibition of Micturition Hyperreflexia in Rodent Models?

2005 ◽  
Vol 173 (4S) ◽  
pp. 44-45
Author(s):  
Quan-Ming Zhu ◽  
Dong-Qing Hu ◽  
David R. Blue ◽  
Philip A. Nunn ◽  
Anthony P.D.W. Ford
Keyword(s):  
Gabab Receptors ◽  
Rodent Models
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