5-HT1A receptor agonist-mediated protection from MPTP toxicity in mouse and macaque models of Parkinson's disease

@article{Bzard20065HT1ARA,
  title={5-HT1A receptor agonist-mediated protection from MPTP toxicity in mouse and macaque models of Parkinson's disease},
  author={Erwan B{\'e}zard and Irene Gerlach and Rosario Moratalla and Christian Gross and Reinhard Jork},
  journal={Neurobiology of Disease},
  year={2006},
  volume={23},
  pages={77-86}
}
Excitotoxicity-mediated cell death is involved in Parkinson's disease (PD). 5-HT1A receptor agonists can protect from such mechanisms. The current study demonstrates that the 5-HT1A agonists BAY 639044 and repinotan have neuroprotective effects in a subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. In addition, we also show that both compounds delay the appearance of parkinsonian motor abnormalities in a MPTP monkey model that recapitulates the progressive nature… 
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Rotigotine treatment partially protects from MPTP toxicity in a progressive macaque model of Parkinson's disease
TLDR
The data suggest that rotigotine exerts partial protection but that conventional imaging would not be able to identify such protection, while the protection of nerve terminals was not detected using SPECT.
Combined 5-HT1A and 5-HT1B receptor agonists for the treatment of L-DOPA-induced dyskinesia.
TLDR
The results demonstrate the existence of a potent synergistic effect between 5- HT(1A) and 5-HT(1B) agonists in their ability to dampen l-DOPA-induced dyskinesia in the MPTP-treated macaques.
Dopamine Transporter Binding Is Unaffected by L-DOPA Administration in Normal and MPTP-Treated Monkeys
TLDR
Data indicate that L-DOPA does not induce modifications of DAT expression detectable by SPECT of by DAT binding autoradiography, suggesting that differences between clinical assessment and radiotracer imaging in clinical trials may not be specifically related to L- DOPA treatment.
Targeting 5-HT1A receptors in astrocytes to protect dopaminergic neurons in parkinsonian models
TLDR
A promising therapeutic strategy of neuroprotection against oxidative stress and progressive dopaminergic neurodegeneration is provided by demonstrating the efficacy of targeting 5-HT1A receptors in astrocytes.
Different Alterations of Agonist and Antagonist Binding to 5-HT1A Receptor in a Rat Model of Parkinson's Disease and Levodopa-Induced Dyskinesia: A microPET Study.
TLDR
The data suggest that agonist and antagonist 5-HT1A receptor-binding sites are differently modified in Parkinson's disease and levodopa-induced dyskinesia and emphasize the need to characterize this state using agonist radiotracers in physiological and pathological conditions.
Effects of coincident 5-HT1A receptor stimulation and NMDA receptor antagonism on l-DOPA-induced dyskinesia and rotational behaviors in the hemi-parkinsonian rat
TLDR
Combined subthreshold doses of ±8-OH-DPAT and MK-801 dose-dependently decreased l-DOPA-induced AIMs without affecting rotations and indicate a functional interaction between 5-HT1AR and NMDAR that may improve pharmacological treatment of PD patients.
Early prenatal exposure to MPTP does not affect nigrostrial neurons in macaque monkey
TLDR
The ultimate effects of MPTP intoxication of a female macaque monkey, which unraveled to be pregnant after parkinsonism had developed, upon its fetus is reported, suggesting that early prenatal intoxication does not destroy nigrostriatal neurons, most likely because dopamine neurons had not developed yet when exposed to MPTP.
Serotonin 1A Receptors on Astrocytes as a Potential Target for the Treatment of Parkinson’s Disease
TLDR
The neuroprotective properties of astrocytes targeting certain molecules related to PD are summarized and new promising therapeutic strategies based on neuroprotection against oxidative stress and prevention of dopaminergic neurodegeneration are discussed.
Animal models of Parkinson's disease: a source of novel treatments and clues to the cause of the disease
TLDR
The MPTP‐treated primate model of PD, which closely mimics the clinical features of PD and in which all currently used anti‐parkinsonian medications have been shown to be effective, is undoubtedly the most clinically‐relevant of all available models.
The differential effects of 5-HT1A receptor stimulation on dopamine receptor-mediated abnormal involuntary movements and rotations in the primed hemiparkinsonian rat
TLDR
The present findings indicate that 5-HT(1A)R stimulation reduces AIMs induced by D1R, D2R and l-DOPA administration while its effects on DA agonist-induced rotations were receptor-dependent, suggesting that direct 5- HT(1 a)R and DA receptor interactions may contribute to the unique profile of 5-ht(1a)R agonists for the improvement of PD treatment.
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