Parkinsonian akinesia, rigidity and tremor in the monkey

Pechadre, J. C.; Larochelle, L.; Poirier, Louis

doi:10.1016/0022-510x(76)90100-3

Cited by 70 publications

(15 citation statements)

References 19 publications

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“…In contrast, typical MPTP dosing regimens cause profound DA depletion with little effect on LC neurons or NE content in mice (10,(35)(36)(37)(38). Furthermore, primate models that attempt to create a ''pure'' dopaminergic loss with intrastriatal/intranigral toxin injections typically produce only sensorimotor deficits and do not recapitulate the cardinal symptoms of PD (e.g., resting tremor and akinesia) (39,40). The integrity of the noradrenergic system is not commonly addressed in mouse MPTP studies, and we suspect that differences in noradrenergic damage across strains and dosing regimens contribute to the variability in reported behavioral results in MPTP-treated mice.…”

Section: Discussionmentioning

confidence: 99%

Norepinephrine loss produces more profound motor deficits than MPTP treatment in mice

Rommelfanger¹,

Edwards

Freeman

et al. 2007

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

176

116

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Although Parkinson's disease (PD) is characterized primarily by loss of nigrostriatal dopaminergic neurons, there is a concomitant loss of norepinephrine (NE) neurons in the locus coeruleus. Dopaminergic lesions induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are commonly used to model PD, and although MPTP effectively mimics the dopaminergic neuropathology of PD in mice, it fails to produce PD-like motor deficits. We hypothesized that MPTP is unable to recapitulate the motor abnormalities of PD either because the behavioral paradigms used to measure coordinated behavior in mice are not sensitive enough or because MPTP in the absence of NE loss is insufficient to impair motor control. We tested both possibilities by developing a battery of coordinated movement tests and examining motor deficits in dopamine ␤-hydroxylase knockout (Dbh؊/؊) mice that lack NE altogether. We detected no motor abnormalities in MPTP-treated control mice, despite an 80% loss of striatal dopamine (DA) terminals. Dbh؊/؊ mice, on the other hand, were impaired in most tests and also displayed spontaneous dyskinesias, despite their normal striatal DA content. A subset of these impairments was recapitulated in control mice with 80% NE lesions and reversed in Dbh؊/؊ mice, either by restoration of NE or treatment with a DA agonist. MPTP did not exacerbate baseline motor deficits in Dbh؊/؊ mice. Finally, striatal levels of phospho-ERK-1/2 and ⌬FosB/FosB, proteins which are associated with PD and dyskinesias, were elevated in Dbh؊/؊ mice. These results suggest that loss of locus coeruleus neurons contributes to motor dysfunction in PD.dopamine ͉ Parkinson's disease ͉ dyskinesias ͉ dopamine ␤-hydroxylase P arkinson's disease (PD) affects Ϸ1% of the world's aging population (1). Despite this high prevalence and intensive research into its origins, the etiology of PD remains largely unknown. The disease is characterized by degeneration of dopamine (DA) neurons in the substantia nigra pars compacta (SN), and symptoms, which tend to manifest when Ϸ80% of striatal DA is lost, include bradykinesia, postural instability, rigidity, and resting tremor. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin, is known to produce parkinsonism in humans and causes severe DA loss in animals (2). Because of its ability to recapitulate the neuropathology of PD, MPTP is used widely in PD research. However, MPTP has been unable to reliably reproduce the motor symptoms of PD in mice, which limits the utility of MPTP-treated mice as an animal model of the disease (3). Differences in mouse strain and experimental paradigms may at least partially account for these inconsistencies.Despite the focus on DA, PD is more accurately described as a multisystem disorder that features a profound albeit underappreciated loss of locus coeruleus (LC) neurons, as well as variable damage to other brain regions (4-6). Postmortem studies indicate that neuronal degeneration in the LC is comparable to that in the substantia nigra pars compacta, and that it may a...

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Section: Discussionmentioning

confidence: 99%

Norepinephrine loss produces more profound motor deficits than MPTP treatment in mice

Rommelfanger¹,

Edwards

Freeman

et al. 2007

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

176

116

View full text Add to dashboard Cite

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“…The correct figure is printed here. Akinesia is a characteristic symptom of Parkinson disease (1-6), which typically involves pathology in the nigrostriatal dopaminergic system (1,2,4,5,(7)(8)(9). In some patients, a paradoxical "festination" can coexist with akinesia.…”

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confidence: 99%

Galloping induced by pontine tegmentum damage in rats: a form of "Parkinsonian festination" not blocked by haloperidol.

Cheng

Schallert

Ryck

et al. 1981

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

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Localized lesions or local applications of gamma-aminobutyric acid (GABA) in the nucleus reticularis tegmenti pontis (NRTP) of rats cause rapidly accelerating forward locomotion. Such "festination" can coexist with blockade of the dopamine system. We suggest that (i) the akinesia produced by dopamine deficiency results at least in part from release of excessive inhibition of locomotion by a neural system whose final common inhibitory path includes the region of the NRTP and (ii) when it occurs in addition to nigrostriatal damage, destruction in the region of the NRTP might be the cause of a form of festination seen in some patients suffering from Parkinsonism.

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“…A lower LCGU indicates that the function of the VTA is impaired in rolling mice. Electric lesions of the VTA induce several abnormal behaviours including hypereactivity (LeMoal et al, 1976;Trovero et al, 1992), postural tremor (Poirier, 1960) or tremor with rigidity (Pechadre et al, 1976). In agreement with this, RMN often exhibited abnormal movement of the hind limbs.…”

Section: Behavioural Studymentioning

confidence: 54%

Anti‐ataxic effects of TRH and its analogue, TA‐0910, in Rolling mouse Nagoya by metabolic normalization of the ventral tegmental area

Kawakami¹,

Watanabe²,

Asai³

et al. 1995

British J Pharmacology

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1 The mechanism of the anti-ataxic action of thyrotropin-releasing hormone (TRH) and its analogue, TA-0910, in the Rolling mouse Nagoya (RMN), an ataxic mutant mouse, has been investigated.2 TRH (30 mg kg-', i.p.) and TA-0910 (3 mg kg-', i.p.) reduced the fall index (number of falls/ spontaneous motor activity), an index of ataxia, 10-30 and 10-60 min after administration, respectively. 3 Relative local cerebral glucose utilization (LCGU) in the cerebellum and ventral tegmental area (VTA) of the rolling mouse was significantly smaller than that in normal animals. TRH (30 mg kg-', i.p.) and TA-0910 (3 mg kg-', i.p.) increased the relative LCGU value of the VTA but not of the cerebellum in rolling mice to the level of normal animals. 4 These results suggest that the ataxia of the rolling mouse may be due to dysfunction of the cerebellum and VTA, and that amelioration by TRH and TA-0910 could result from metabolic normalization of the VTA.

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Parkinsonian akinesia, rigidity and tremor in the monkey

Cited by 70 publications

References 19 publications

Norepinephrine loss produces more profound motor deficits than MPTP treatment in mice

Norepinephrine loss produces more profound motor deficits than MPTP treatment in mice

Galloping induced by pontine tegmentum damage in rats: a form of "Parkinsonian festination" not blocked by haloperidol.

Anti‐ataxic effects of TRH and its analogue, TA‐0910, in Rolling mouse Nagoya by metabolic normalization of the ventral tegmental area

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