Transgenic rat model of Huntington's disease

Hörsten, Stephan von; Schmitt, Imke; Nguyen, Huu Phuc; Holzmann, Carsten; Schmidt, Thorsten; Walther, Thomas; Bäder, Michael; Pabst, Reinhard; Kobbe, Philipp; Krotova, Jana; Stiller, Detlef; Kask, Ants; Vaarmann, Annika; Rathke-Hartlieb, Silvia; Schulz, Jörg B.; Grasshoff, Ute; Bauer, Ingrid; Vieira-Saecker, Ana; Paul, Martin; Jones, Lesley; Lindenberg, Katrin S.; Landwehrmeyer, G. Bernhard; Bauer, Andreas; Li, Shengbo Eben; Rieß, Olaf

doi:10.1093/hmg/ddg075

Cited by 280 publications

(65 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After 4 days of training (trial duration of 120 s twice daily with an intertrial interval of 90 min) at a constant speed of 14 rpm, animals were subjected to the apparatus for 4 days, and the rotation speed was constantly increased (4-40 rpm) over a 5-min time period. The latency to fall off the rod and the actual rotation speed were recorded (25). Beam walking test.…”

Section: Methodsmentioning

confidence: 99%

Y1 receptors regulate aggressive behavior by modulating serotonin pathways

Karl

Lin

Schwarzer

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Neuropeptide Y (NPY) is pivotal in the coordinated regulation of food intake, growth, and reproduction, ensuring that procreation and growth occur only when food is abundant and allowing for energy conservation when food is scant. Although emotional and behavioral responses from the higher brain are known to be involved in all of these functions, understanding of the coordinated regulation of emotion͞behavior and physiological functions is lacking. Here, we show that the NPY system plays a central role in this process because ablation of the Y1 receptor gene leads to a strong increase in territorial aggressive behavior. After exposure to the resident-intruder test, expression of c-fos mRNA in Y1-knockout mice is significantly increased in the medial amygdala, consistent with the activation of centers known to be important in regulating aggressive behavior. Expression of the serotonin [5-hydroxytryptamine (5-HT)] synthesis enzyme tryptophan hydroxylase is significantly reduced in Y1-deficient mice. Importantly, treatment with a 5-HT-1A agonist, (؎)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide, abolished the aggressive behavior in Y1-knockout mice. These results suggest that NPY acting through Y1 receptors regulates the 5-HT system, thereby coordinately linking physiological survival mechanisms such as food intake with enabling territorial aggressive behavior. Aggression is a fundamental behavior that has evolved to help organisms compete for limited resources and, therefore, to guarantee survival of the species. Behavioral, pharmacological, and genetic studies have shown that specific neuronal circuits and various neurotransmitters and hormones modulate impulsiveness and aggressiveness in animal models as well as humans (1, 2). In particular, brain areas such as the olfactory bulb, the prefrontal cortex, the amygdala, several hypothalamic structures, and the area of the periaqueductal gray have been implicated in the regulation of emotion-and aggression-related behavior (3).Although science has begun to reveal these neuronal circuits involved in regulating aggression, little is known about the molecular mechanisms that link particular physiological events with appropriate aggressive behavior. For example, aggressive behavior could be advantageous for hunting or defending a territory, especially when an individual is hungry and there is competition for a limited food supply. Similarly, aggression in males of many species can be advantageous in attracting the fittest partner. However, the mechanisms by which aggression and appetite or aggression and sexual drive are coordinately regulated are unknown.We hypothesized that the evolutionary conserved neuropeptide Y (NPY) and its Y-receptor system may fulfill this important role of integrating aggressive behavior, especially territorial aggressive behavior, with other survival-related physiological functions. NPY is widely expressed in the brain, including the cerebral cortex, the hippocampus, the hypothalamus, the septum, and the brainstem (4). Central NPY syst...

show abstract

Section: Methodsmentioning

confidence: 99%

Y1 receptors regulate aggressive behavior by modulating serotonin pathways

Karl

Lin

Schwarzer

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Differences between rats and mice have also been described in relation to modelling HD, with some studies suggesting that the rat provides a more faithful model of the human disease than the mouse (von Horsten et al, 2003), especially in terms of progression, which seems much faster in mice than in rats (and humans). However, this conclusion is mainly based on a comparison with the R6/2 mouse model, which shows a very fast-progressing and severe phenotype (Mangiarini et al, 1996), even compared to other mouse models.…”

Section: Rats and Mice As Models For Human Neurological And Psychiatrmentioning

confidence: 99%

Rodent models in neuroscience research: is it a rat race?

Ellenbroek

Youn

2016

Disease Models &Amp; Mechanisms

488

379

View full text Add to dashboard Cite

Rodents (especially Mus musculus and Rattus norvegicus) have been the most widely used models in biomedical research for many years. A notable shift has taken place over the last two decades, with mice taking a more and more prominent role in biomedical science compared to rats. This shift was primarily instigated by the availability of a much larger genetic toolbox for mice, particularly embryonic-stem-cell-based targeting technology for gene disruption. With the recent emergence of tools for altering the rat genome, notably genome-editing technologies, the technological gap between the two organisms is closing, and it is becoming more important to consider the physiological, anatomical, biochemical and pharmacological differences between rats and mice when choosing the right model system for a specific biological question. The aim of this short review and accompanying poster is to highlight some of the most important differences, and to discuss their impact on studies of human diseases, with a special focus on neuropsychiatric disorders.

show abstract

“…For this purpose, we investigated the mitochondrial function in a newly generated transgenic HD rat strain with 51 glutamine repeats (htt 51Q ) (20). In contrast to htt Q150 R6/2 mice, a model of the juvenile form of HD (21), the htt 51Q rat strain exhibits specifically an adult-related onset of the neurological HD phenotype (20).…”

Section: Huntington Disease (Hd)mentioning

confidence: 99%