An experimental model for Huntington's chorea?

Clinically, Huntington's disease (HD) is well known for the predominant motor symptom chorea, which is a hyperkinetic motor disorder. The only experimental model currently described in the literature, as far as we are aware of, exhibiting hyperkinetic movements is the transgenic rat model of HD. We assessed and characterized these hyperkinetic movements in detail and investigated the effect of tetrabenazine (TBZ) treatment.

Transgenic Rat Models of Huntington's Disease.

Several animal models for Huntington's disease (HD) have been created in order to investigate mechanisms of disease, and to evaluate the potency of novel therapies. Here, we describe the characteristics of the two transgenic rat models: transgenic rat model of HD (fragment model) and the Bacterial Artificial Chromosome HD model (full-length model). We discuss their genetic, behavioural, neuropathological and neurophysiological features.

Lessons learned from the transgenic Huntington's disease rats.

Huntington's disease (HD) is a fatal inherited disorder leading to selective neurodegeneration and neuropsychiatric symptoms. Currently, there is no treatment to slow down or to stop the disease. There is also no therapy to effectively reduce the symptoms.

Metabolic and electrophysiological changes in the basal ganglia of transgenic Huntington's disease rats.

Huntington's disease (HD) is characterized by neuronal loss in the striatum, ultimately leading to an 'imbalance' in the electrical activity of the basal ganglia-thalamocortical circuits. To restore this 'imbalance' in HD patients, which is held responsible for (some) of the motor symptoms, different basal ganglia nuclei have been targeted for surgical therapies, such as ablative surgery and deep brain stimulation. However, evidence to target brain nuclei for surgical therapies in HD is lacking.

Mild dopaminergic lesions are accompanied by robust changes in subthalamic nucleus activity.

The subthalamic nucleus (STN) is a major player in the input and output of the basal ganglia motor circuitry. The neuronal regular firing pattern of the STN changes into a pathological bursting mode in both advanced Parkinson's disease (PD) and in PD animals models with severe dopamine depletion. One of the current hypothesis, based on clinical and experimental evidence, is that this typical burst activity is responsible for some of the principal motor symptoms.

Memory deficits in the transgenic rat model of Huntington's disease.

Memory deficits are common in patients with Huntington's disease (HD) and have a substantial impact on the quality of life of patients and their relatives. A good model resembling the human memory deficits is needed for research purposes. In this study we investigated the memory function of the transgenic rat model of Huntington's disease (tgHD) in the object location (OLT) and the object recognition task (ORT).

Unchanged expression of the ceramide transfer protein in the acute 6-OHDA neurodegenerative model.

Ceramides are lipids that are abundant in brain tissue where they have an important structural role in cellular membranes. Ceramides are also powerful intracellular signalling molecules controlling cell death, growth and differentiation. So far, the ceramide transfer protein (CERT), a shorter splice variant of the Goodpasture antigen-binding protein (GPBP), is the only known protein with the ability to shuttle ceramide from the endoplasmic reticulum to the Golgi apparatus.

Motor and non-motor behaviour in experimental Huntington's disease.

In this study, we investigated motor and non-motor behaviour in the transgenic rat model of Huntington's disease (tgHD). In particular, we were interested in the development and changes of motor and non-motor features (anxiety, motivation and hedonia) of disease over time and their interactions. We found tgHD animals to be hyperkinetic in the open field test compared to their wild-type littermates at all ages tested, which was accompanied by reduced anxiety-like behaviour in the open field test and the elevated zero maze, but not in the home cage emergence test.

Increased plasma corticosterone levels after periaqueductal gray stimulation-induced escape reaction or panic attacks in rats.

The hypothalamo-pituitary-adrenal (HPA) axis is involved in stress, depression and anxiety. Controversy exists on HPA axis activation during panic attacks (PAs). We examined whether the HPA axis is involved in the escape or panic-like response in an animal model of PAs induced by electrical stimulation of the dorsolateral periaqueductal gray (dlPAG) in rats.

Experimental deep brain stimulation in animal models.

DEEP BRAIN STIMULATION (DBS) as a therapy in neurological and psychiatric disorders is widely applied in the field of functional and stereotactic neurosurgery. In this respect, experimental DBS in animal models is performed to evaluate new indications and new technology. In this article, we review our experience with the concept of experimental DBS, including its development and validation.

Attenuation of fear-like response by escitalopram treatment after electrical stimulation of the midbrain dorsolateral periaqueductal gray.

Electrical stimulation of the dorsolateral periaqueductal gray (dlPAG) has frequently been shown to induce escape and freezing/decreased locomotion responses which mimic panic- and fear-like behaviour. In the present study we tested whether such spontaneous fear-like behaviour could be observed in an open-field test 12 h after dlPAG stimulation. Further, we tested whether this fear-like behaviour could be attenuated by acute or chronic administration of buspirone and escitalopram.

Hyperdopaminergic status in experimental Huntington disease.

Huntington disease has been linked to increased dopaminergic neurotransmission in the striatum, and clinical studies have demonstrated that the associated chorea can be treated with dopamine antagonist or dopamine-depleting drugs. The origin of this hyperdopaminergic status is unknown. Because substantia nigra pars compacta and the ventral tegmental area are the main sources of striatal dopamine input, we hypothesized that changes in these regions relate to striatal dopaminergic alterations.

Deep brain stimulation of the nucleus accumbens shell increases impulsive behavior and tissue levels of dopamine and serotonin.

The nucleus accumbens (NAc) is gaining interest as a target for deep brain stimulation (DBS) in refractory neuropsychiatric disorders with impulsivity as core symptom. The nucleus accumbens is composed of two subterritories, core and shell, which have different anatomical connections. In animal models, it has been shown that DBS of the NAc changes impulsive action.

Bilateral high frequency stimulation of the subthalamic nucleus normalizes COX activity in the substantia nigra of Parkinsonian rats.

Part of the mechanism underlying the therapeutic effect of subthalamic nucleus (STN) high frequency stimulation (HFS) involves the activity of the basal ganglia output structures. The general idea is that STN's burst activity leads to an increased activity of the basal ganglia output nuclei and that HFS reverses this. However, the published data sets conflict.

Cognitive and limbic effects of deep brain stimulation in preclinical studies.

The use of deep brain stimulation (DBS) to control severely disabling neurological and psychiatric conditions is an exciting and fast emerging area of neuroscience. Deep brain stimulation has generally the same clinical effects as a lesion with respect to the improvement of clinical disability, but has more advantages such as its adjustability and reversibility. To this day, fundamental knowledge regarding the application of electrical currents to deep brain structures is far from complete.

Increased electrical and metabolic activity in the dorsal raphe nucleus of Parkinsonian rats.

Serotonin (5-HT) containing neurons in the dorsal raphe nucleus (DRN) may play important roles in Parkinson's disease (PD). This study investigated neural and metabolic activity of the DRN in animal PD models based on dopamine depletion. The data show both increased firing rate of DRN 5-HT neurons and increased cytochrome oxidase activity in dopamine-depleted rats, as compared to controls.

Motor and cognitive improvement by deep brain stimulation in a transgenic rat model of Huntington's disease.

Altered activity of the globus pallidus externus (GPe) is responsible for at least part of the cognitive and motor symptoms of Huntington's disease (HD). In this study, we tested the hypothesis that bilateral globus pallidus (GP; equivalent of GPe in primates) deep brain stimulation (DBS) improves cognitive and motor symptoms in the first transgenic rat model of HD (tgHD rats). GP DBS with clinically relevant stimulation parameters resulted in a significant improvement of cognitive dysfunction and reduced the number of choreiform movements.

Progressive deterioration of reaction time performance and choreiform symptoms in a new Huntington's disease transgenic ratmodel.

We tested the hypothesis that a recently developed transgenic rat model of Huntington's disease (tgHD rats) showed an age-and genotype-dependent change in psychomotor performance and in the frequency of choreiform movements similar to HD patients. Wild type and tgHD (homozygotic and heterozygotic) rats were behaviorally tested at an age of 15 and 20 months. Our results show that tgHD rats exhibit an age-, and genotype-dependent deterioration of the psychomotor performance and choreiform symptoms, closely mimicking the clinical time course changes of psychomotor symptoms of HD patients.