Changes in brainstem serotonergic and dopaminergic cell populations in experimental and clinical Huntington’s disease

Jahanshahi, Ali; Vlamings, Rinske; Roon‐Mom, Willeke M. C. van; Faull, Richard L.M.; Waldvogel, Henry J.; Janssen, Mark; Yakkioui, Youssef; Zeef, Dagmar H.; Kocabıcak, Ersoy; Steinbusch, Harry W.M.; Temel, Yasin

doi:10.1016/j.neuroscience.2013.01.071

Cited by 26 publications

(22 citation statements)

References 44 publications

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“…In homozygous tgHD rats, recent studies found enhanced TH levels in the dorsal and ventral triatum (Jahanshahi et al, 2010, 2013), in line with postmortem clinical data (Bird et al, 1980; Spokes, 1980). Furthermore, a reduction in striatal D1-receptor density was found in 14 months old tgHD rats (Bode et al, 2008), as well as a decrease in striatal D1 and D2 receptor binding at the age of 24 months (Bauer et al, 2005; Von Hörsten et al, 2003).…”

Section: Discussionsupporting

confidence: 62%

“…Twelve months old tgHD rats show an alteration of synaptic plasticity of the prefronto-striatal pathway (Höhn et al, 2011) as well as a reduced surface of the CeA associated with reduced affective responses to motivational events (Faure et al, 2011). TgHD rats (11 months old) also show DA alterations indicated by enhanced TH levels in the dorsal and ventral striatum (Jahanshahi et al, 2010, 2013), in line with postmortem clinical data (Bird et al, 1980; Spokes, 1980). …”

Section: Discussionsupporting

confidence: 60%

“…Furthermore, a reduction in striatal D1-receptor density was found in 14 months old tgHD rats (Bode et al, 2008), as well as a decrease in striatal D1 and D2 receptor binding at the age of 24 months (Bauer et al, 2005; Von Hörsten et al, 2003). A reduction of serotonin-containing cells and an increase of dopamine-containing cells were also found in the dorsal raphe nucleus in both human and tgHD rat tissues, inducing a reduced level of serotonin expression in the medial PFC (Jahanshahi et al, 2013). All these results indicate amygdala-prefronto-striatal circuits’ dysfunction in HD patients and tgHD rats, with associated dopamine dysregulation.…”

Section: Discussionmentioning

confidence: 99%

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Impaired Decision Making and Loss of Inhibitory-Control in a Rat Model of Huntington Disease

Massioui

Lamirault

Yagüe

et al. 2016

Front. Behav. Neurosci.

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Cognitive deficits associated with Huntington disease (HD) are generally dominated by executive function disorders often associated with disinhibition and impulsivity/compulsivity. Few studies have directly examined symptoms and consequences of behavioral disinhibition in HD and its relation with decision-making. To assess the different forms of impulsivity in a transgenic model of HD (tgHD rats), two tasks assessing cognitive/choice impulsivity were used: risky decision-making with a rat gambling task (RGT) and intertemporal choices with a delay discounting task (DD). To assess waiting or action impulsivity the differential reinforcement of low rate of responding task (DRL) was used. In parallel, the volume as well as cellular activity of the amygdala was analyzed. In contrast to WT rats, 15 months old tgHD rats exhibited a poor efficiency in the RGT task with difficulties to choose advantageous options, a steep DD curve as delays increased in the DD task and a high rate of premature and bursts responses in the DRL task. tgHD rats also demonstrated a concomitant and correlated presence of both action and cognitive/choice impulsivity in contrast to wild type (WT) animals. Moreover, a reduced volume associated with an increased basal cellular activity of the central nucleus of amygdala indicated a dysfunctional amygdala in tgHD rats, which could underlie inhibitory dyscontrol. In conclusion, tgHD rats are a good model for impulsivity disorder that could be used more widely to identify potential pharmacotherapies to treat these invasive symptoms in HD.

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Section: Discussionsupporting

confidence: 62%

Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Impaired Decision Making and Loss of Inhibitory-Control in a Rat Model of Huntington Disease

Massioui

Lamirault

Yagüe

et al. 2016

Front. Behav. Neurosci.

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“…3 The number of c-fos cells in the a VTA and b SNc after DBS. No significant difference was found in the c-Fos positive levels between the groups stimulated in the mammilothalamic Tract (MTT, n = 5), in the anterior nucleus of the thalamus (ANT, n = 5), in the entorhinal cortex (EC, n = 6), and the sham stimulated group (n = 3) Brain Struct Funct increased number of dopaminergic neurons, which was accompanied by a decreased number of serotonergic neurons in the dorsal raphe nucleus (Jahanshahi et al 2013), suggesting that a pathological condition such as genetic mutation can lead to neurotransmitter respecification as well. These studies show that neurons, in the brain are not fixed, but respond to environmental stimuli and behaviors.…”

Section: Discussionmentioning

confidence: 97%

Increased number of TH-immunoreactive cells in the ventral tegmental area after deep brain stimulation of the anterior nucleus of the thalamus

et al. 2014

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Dopamine (DA) has been long implicated with the processes of memory. In long-term memory, the hippocampus and ventral tegmental area (VTA) use DA to enhance long-term potentiation, while prefrontal DA D1 receptors are involved in working memory. Deep brain stimulation (DBS) of specific brain areas have been shown to affect memory impairments in animal models. Here, we tested the hypothesis that DBS could reverse memory impairments by increasing the number of dopaminergic cells in the VTA. Rats received DBS at the level of the mammillothalamic tract, the anterior nucleus of the thalamus, and entorhinal cortex before euthanasia. These regions are part of the so-called memory circuit. Brain sections were processed for c-Fos and tyrosine hydroxylase (TH) immunocytochemistry in the VTA and the substantia nigra pars compacta (SNc). c-Fos, TH and c-Fos/TH immunoreactive cells were analyzed by means of stereology and confocal microscopy. Our results showed that DBS of the anterior nucleus of the thalamus induced substantial higher numbers of TH-immunoreactive cells in the VTA, while there were no significant differences between the experimental groups in the number of TH immunoreactive cells in the SNc, c-Fos immunoreactive cells and c-Fos/TH double-labeled cells in both the SNc and VTA. Our findings suggest a phenotypic switch, or neurotransmitter respecification, of DAergic cells specifically in the VTA which may be induced by DBS in the anterior nucleus of the thalamus.

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“…1). Another neuropathological finding in this animal model was the significantly higher number of dopaminergic cells in the substantia nigra pars compacta, ventral tegmental area and the dorsal raphe nucleus, leading to an enhanced dopamine release into the dorsal and ventral striatum (Jahanshahi et al 2010;Jahanshahi et al 2013). This hyperdopaminergic status has been linked to the choreiform movements observed in this model (Fig.…”

Section: Neuropathological Phenotypementioning

confidence: 88%

Transgenic Rat Models of Huntington’s Disease

Casaca-Carreira

Jahanshahi

Zeef

et al. 2013

Behavioral Neurobiology of Huntington's Disease and Parkinson's Disease

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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.

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Changes in brainstem serotonergic and dopaminergic cell populations in experimental and clinical Huntington’s disease

Cited by 26 publications

References 44 publications

Impaired Decision Making and Loss of Inhibitory-Control in a Rat Model of Huntington Disease

Impaired Decision Making and Loss of Inhibitory-Control in a Rat Model of Huntington Disease

Increased number of TH-immunoreactive cells in the ventral tegmental area after deep brain stimulation of the anterior nucleus of the thalamus

Transgenic Rat Models of Huntington’s Disease

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