Emerging dysfunctions consequent to combined monoaminergic depletions in parkinsonism

Delaville, Claire; Chetrit, Jonathan; Abdallah, Khaled; Morin, Stéphanie; Cardoit, Laura; Deurwaerdère, Philippe De; Benazzouz, Abdelhamid

doi:10.1016/j.nbd.2011.10.023

Cited by 98 publications

(85 citation statements)

References 65 publications

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“…and increased motor deficits (Archer and Fredriksson, 2006;Bing et al, 1994;Fornai et al, 1997;Mavridis et al, 1991). In our study, increased motor impairments did not seem to be caused by increased DA neuron cell loss, which is in agreement with some studies (Delaville et al, 2012;Pifl et al, 2013;Rommelfanger et al, 2007). Other studies have reported increased DA neurodegeneration, or increased loss of striatal DA, in double lesioned animals (Archer and Fredriksson, 2006;Bing et al, 1994;Fornai et al, 1997;Mavridis et al, 1991;Schmidt, 2003, 2004).…”

Section: Discussionsupporting

confidence: 92%

“…Regardless of the magnitude of DA degeneration in nigra and striatum, single lesioned rats did not show any impairment in retrieving and eating pellets, whereas most of the double lesioned rats showed impairments in both parameters. In previous studies in rats, using 6-OHDA lesions in combination with DSP-4, the behavioural deficits induced by the 6-OHDA lesion was largely unaffected by the DSP-4 treatment (Delaville et al, 2012;Schmidt, 2003, 2004), although one of them reported reduced open field activity in 6-OHDA+DSP-4 double lesioned rats (Srinivasan and Schmidt, 2004). In mouse and monkey models the effects of NA degeneration, induced by DSP-4 or 6-OHDA into LC, have been more consistent and pronounced, especially when MPTP has been employed as a DA toxin.…”

Section: Discussionmentioning

confidence: 86%

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Noradrenaline neuron degeneration contributes to motor impairments and development of L-DOPA-induced dyskinesia in a rat model of Parkinson's disease

Shin

Rogers

Devoto

et al. 2014

Experimental Neurology

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Parkinson's disease (PD) is characterized by progressive loss of dopaminergic (DA) neurons in the substantia nigra. However, studies of post-mortem PD brains have shown that not only DA neurons but also the noradrenergic (NA) neurons in the locus coeruleus degenerate, and that the NA neurodegeneration may be as profound, and also precede degeneration of the midbrain DA neurons. Previous studies in animal models of PD have suggested that loss of forebrain NA will add to the development of motor symptoms in animals with lesions of the nigrostriatal DA neurons, but the results obtained in rodents have been inconclusive due to the shortcomings of the toxin, DSP-4, used to lesion the NA projections. Here, we have developed an alternative double-lesion paradigm using injections of 6-OHDA into striatum in combination with intraventricular injections of a powerful NA immunotoxin, anti-DBH-Saporin, to eliminate the NA neurons in the brain.Animals with combined DA and NA lesions were more prone to develop L-DOPAinduced dyskinesia, even at low L-DOPA doses, and they performed significantly worse in tests of reflexive and skilled paw use, the stepping and staircase tests, compared to DA-only lesioned rats. Post-mortem analysis revealed that NA depletion did not affect the degree of DA depletion, or the loss of tyrosine hydroxylase-positive innervation in the striatum. Cell loss in the substantia nigra was similar in both single and double lesioned animals, showing that the worsening effect was not due to increased loss of nigral DA neurons. The results show that damage to the NA neurons in the central nervous system contributes to the development of motor impairments and the appearance of L-DOPAinduced dyskinesia in 6-OHDA lesioned rats, and provide support for the view that the development of motor symptoms and dyskinetic side effects in PD patients reflects the combined loss of midbrain DA neurons and NA neurons.3

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 86%

Noradrenaline neuron degeneration contributes to motor impairments and development of L-DOPA-induced dyskinesia in a rat model of Parkinson's disease

Shin

Rogers

Devoto

et al. 2014

Experimental Neurology

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“…Although depression is a common non-motor symptom in PD, previous studies into depressive-like behaviors in different rat models of PD were less consistent (Winter et al, 2007;Branchi et al, 2008;Tadaiesky et al, 2008;Eskow Jaunarajs et al, 2010Santiago et al, 2010Santiago et al, , 2014Zhang et al, 2011;Delaville et al, 2012;Sourani et al, 2012;Carvalho et al, 2013;Hui et al, 2014). The discrepancy could be related to the site of 6-OHDA injection, the extent of DA depletion, unilateral or bilateral lesions, used depression paradigms and time frame for the behavior tests.…”

Section: Depressive-like Behaviors Involve Increased Burst-firing Actmentioning

confidence: 98%

“…Previous studies into depressive-like behaviors in 6-hydroxydopamine (6-OHDA)-lesioned rats have been limited and divergent. These studies reported increased or unchanged depressive-like behaviors in different 6-OHDA rat models of PD (Winter et al, 2007;Branchi et al, 2008;Tadaiesky et al, 2008;Eskow Jaunarajs et al, 2010Santiago et al, 2010Santiago et al, , 2014Zhang et al, 2011;Delaville et al, 2012;Sourani et al, 2012;Carvalho et al, 2013;Hui et al, 2014). Further, a dysfunctional 5-HT system is generally regarded as a risk factor for depression, and accumulating lines of evidences also suggest that degeneration of the nigrostriatal pathway leads to an impairment of 5-HT system, with evidence including the loss of 5-HT neurons, reduction of brain 5-HT content, hyperactivity of 5-HT neurons and alterations in various types of 5-HT receptors (Scholtissen et al, 2006;Wang et al, 2009;Huot et al, 2011).…”

Section: Introductionmentioning

confidence: 98%

Activation of serotonin2C receptors in the lateral habenular nucleus increases the expression of depression-related behaviors in the hemiparkinsonian rat

Han

Zhang

et al. 2015

Neuropharmacology

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“…In vertebrates too, the primary role of DA is not to mediate stress and anxiety. Nevertheless the DA system may act in several regions to accompany or enable stress or anxiety responses, by alterations of motor behavior or of learning and memory (Le Moal and Simon, 1991;Arnsten, 2000;Delaville et al, 2012). Thus, it remains possible that DA could play analogous but yet unknown roles in crayfish as a consequence of stress, but clearly not in ALB in our experimental conditions.…”

Section: Intensity Of Alb and Damentioning

confidence: 99%

Serotonin, but not dopamine, controls stress response and anxiety-like behavior in crayfish, Procambarus clarkii.

Fossat

Bacqué-Cazenave

Deurwaerdère

et al. 2015

Journal of Experimental Biology

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In the animal kingdom, biogenic amines are widespread modulators of the nervous system that frequently interact to control mood. Our previous investigations in crayfish (Procambarus clarkii) have established that stress induces changes in brain serotonin (5-HT) concentrations that are responsible for the appearance of anxiety-like behavior (ALB). Here, we further analyze the roles of 5-HT and another biogenic amine, dopamine (DA), on the crayfish response to stress. We show that the intensity of crayfish ALB depends on the intensity of stressful stimulation and is associated with increased concentrations of 5-HT in the brain. These 5-HT levels were significantly correlated, before, as well as after stress, with those of DA, which were approximately 3-to 5-times less abundant. However, whereas the degree of ALB was clearly correlated with brain 5-HT concentrations, it was not significantly correlated with DA. Moreover, in contrast to injections of 5-HT, DA injections were not able to elicit a stress response or ALB. In addition, 5-HT and DA levels were not modified by treatment with the anxiolytic chlordiazepoxide, confirming that suppression of ALB by this GABA-A receptor ligand acts downstream and is independent of changes in crayfish bioamine levels. Our study also provides evidence that the anxiogenic effect of 5-HT injections can be prevented by a preliminary injection of 5-HT antagonists. Altogether, our results emphasize that the rises in brain concentrations of 5-HT, but not DA, play a role in controlling the induction and the intensity of crayfish ALB.

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Emerging dysfunctions consequent to combined monoaminergic depletions in parkinsonism

Cited by 98 publications

References 65 publications

Noradrenaline neuron degeneration contributes to motor impairments and development of L-DOPA-induced dyskinesia in a rat model of Parkinson's disease

Noradrenaline neuron degeneration contributes to motor impairments and development of L-DOPA-induced dyskinesia in a rat model of Parkinson's disease

Activation of serotonin2C receptors in the lateral habenular nucleus increases the expression of depression-related behaviors in the hemiparkinsonian rat

Serotonin, but not dopamine, controls stress response and anxiety-like behavior in crayfish, Procambarus clarkii.

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