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

  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},

Combined 5-HT1A and 5-HT1B receptor agonists for the treatment of L-DOPA-induced dyskinesia.

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

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.

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.

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

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.

Serotonin 1A Receptors on Astrocytes as a Potential Target for the Treatment of Parkinson’s Disease

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

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.



Absence of MPTP-Induced Neuronal Death in Mice Lacking the Dopamine Transporter

The results shed light on the degenerative process of dopamine neurons and suggest that individual differences in developing Parkinson's disease in human may be related to differences of uptake through the DAT of a yet unidentified neurotoxin.

Effects of Different Schedules of MPTP Administration on Dopaminergic Neurodegeneration in Mice

Compared the effects of different schedules of injection of the same cumulative dose of MPTP, in mice, by measuring tyrosine hydroxylase immunoreactivity in the substantia nigra pars compacta, these mechanisms need to be better understood if chronic models of intoxication that replicate the evolution of human Parkinson's disease more precisely are to be developed.

Bax ablation prevents dopaminergic neurodegeneration in the 1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease

It is shown that the pro-apoptotic protein Bax is highly expressed in the SNpc and that its ablation attenuates SNpc developmental neuronal apoptosis, and it is suggested that targeting Bax may provide protective benefit in the treatment of Parkinson's disease.

Deleterious effects of minocycline in animal models of Parkinson's disease and Huntington's disease

The histopathological outcome demonstrated that minocycline‐treated mice presented significantly more severe neuronal cell loss in the dorsal striatum in the 3‐nitropropionic acid mouse model of HD, and minocyCline blocked 3‐NP‐induced neurotoxicity at certain doses but not at higher doses.

Serotonin 5-HT1A agonist improves motor complications in rodent and primate parkinsonian models

Drugs acting to stimulate 5-HT1A receptors could prove useful in the treatment of the motor response complications in parkinsonian patients.

Blockade of Microglial Activation Is Neuroprotective in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Mouse Model of Parkinson Disease

It is shown that minocycline, an approved tetracycline derivative that inhibits microglial activation independently of its antimicrobial properties, mitigates both the demise of nigrostriatal dopaminergic neurons and the formation of nitrotyrosine produced by MPTP.

Kinetics of nigral degeneration in a chronic model of MPTP-treated mice