Doxycycline restrains glia and confers neuroprotection in a 6‐OHDA Parkinson model
Doxycycline restrains glia and confers neuroprotection in a 6‐OHDA Parkinson model
Where did the research take place?
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Ribeirão Preto, BR · Author affiliation
Department of Morphology, Physiology and Pathology School of Odontology of Ribeirão Preto (FORP) University of São Paulo (USP) Ribeirão Preto SP BrazilLocation evidence
São Paulo, BR · Author affiliation
Department of Morphology, Physiology and Pathology School of Odontology of Ribeirão Preto (FORP) University of São Paulo (USP) Ribeirão Preto SP BrazilLocation evidence
Göttingen, DE · Author affiliation
Department of Molecular Biology of Neuronal Signals Max Planck Institute of Experimental Medicine Göttingen GermanyLocation evidence
Paris, FR · Author affiliation
INSERM UMR 975 – CNRS UMR 7225 Université Pierre et Marie Curie CRICM6 ICM Thérapeutique Expérimentale de la Neurodégénérescence Paris FranceLocation evidence
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Original abstract
Neuron–glia interactions play a key role in maintaining and regulating the central nervous system. Glial cells are implicated in the function of dopamine neurons and regulate their survival and resistance to injury. Parkinson's disease is characterized by the loss of dopamine neurons in the substantia nigra pars compacta, decreased striatal dopamine levels and consequent onset of extrapyramidal motor dysfunction. Parkinson's disease is a common chronic, neurodegenerative disorder with no effective protective treatment. In the 6‐OHDA mouse model of Parkinson's disease, doxycycline administered at a dose that both induces/represses conditional transgene expression in the tetracycline system, mitigates the loss of dopaminergic neurons in the substantia nigra compacta and nerve terminals in the striatum. This protective effect was associated with: (1) a reduction of microglia in normal mice as a result of doxycycline administration per se; (2) a decrease in the astrocyte and microglia response to the neurotoxin 6‐OHDA in the globus pallidus and substantia nigra compacta, and (3) the astrocyte reaction in the striatum. Our results suggest that doxycycline blocks 6‐OHDA neurotoxicity in vivo by inhibiting microglial and astrocyte expression. This action of doxycycline in nigrostriatal dopaminergic neuron protection is consistent with a role of glial cells in Parkinson's disease neurodegeneration. The neuroprotective effect of doxycycline may be useful in preventing or slowing the progression of Parkinson's disease and other neurodegenerative diseases linked to glia function.