Minocycline Inhibition of Microglial Rescues Nigrostriatal Dopaminergic Neurodegeneration Caused by Mutant Alpha-Synuclein Overexpression
Open accessAbstract
Studies indicate that mutant α-synuclein (mαSyn) is involved in the pathogenesis of Parkinson's disease (PD). The mαSyn expression leads to the loss of dopaminergic neurons in the substantia nigra (SN) and consequent motor dysfunctions. Additionally, studies found that PD was accompanied by extensive neuroinflammation of SN. However, it remains unclear as to whether microglia participate in the mαSyn pathology. This issue is addressed by using AAV-mα-Syn (A30P-A53T) to overexpress the human mαSyn in the SN in view of establishing the PD model. Subsequently, minocycline (Mino) was used to inhibit microglia activity, and an interleukin-1 receptor (IL-1R1) antagonist was used to hinder the IL-1R1 function. Finally, immunohistochemistry was used to analyze phosphorylated αSyn (Ser129) and TH-positive cells in the SN. Dopamine levels were analyzed by high performance liquid chromatography. mαSyn overexpression in the SN induced motor dysfunction, decreased striatal dopamine levels, and increased pathological αSyn 12 weeks after AAV injection. The data demonstrated that inhibiting microglial activation or hindering IL-1R1 reversed the persistent motor deficits, neurodegeneration of the nigrostriatal dopaminergic system, and development of Lewy body pathology caused by human mαSyn overexpression in the SN. Additionally, these findings indicate that neuroinflammation promotes the loss of neuronal cells.
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Minocycline inhibition of microglial proliferation and activity increased dopamine levels in mice.
“proliferation and microglial activity, protected mice from dopaminergic neuron loss, increased the dopamine level, and decreased Lewy body pathology in mice23.”
From Microglial inhibition alleviates alpha-synuclein propagation and neurodegeneration in Parkinson’s disease mouse model (2024) · cites this paper as [23]
The Results section ('Mino administration increased the dopamine level,' page unavailable) reports that minocycline increased striatal dopamine in mice with mutant α-synuclein overexpression. The Results also report reduced Iba1-positive microglial cell counts and activation after treatment, but do not establish that minocycline inhibited microglial proliferation specifically. (LLM, conf=0.84)
Experimental — accuracy not yet measuredMinocycline inhibition of microglial proliferation and activity protected mice from dopaminergic neuron loss.
“proliferation and microglial activity, protected mice from dopaminergic neuron loss, increased the dopamine level, and decreased Lewy body pathology in mice23.”
From Microglial inhibition alleviates alpha-synuclein propagation and neurodegeneration in Parkinson’s disease mouse model (2024) · cites this paper as [23]
The Results report that minocycline reduced the number of Iba1-positive microglia and prevented dopaminergic neuron loss in mice with mutant α-synuclein overexpression. They also report higher dopamine levels and reduced Lewy-body pathology. The paper describes inhibition of microglial activation and function, but does not establish that minocycline inhibited microglial proliferation specifically (page numbers unavailable in our copy). (LLM, conf=0.84)
Experimental — accuracy not yet measuredMinocycline inhibition of microglial proliferation and activity decreased Lewy body pathology in mice.
“proliferation and microglial activity, protected mice from dopaminergic neuron loss, increased the dopamine level, and decreased Lewy body pathology in mice23.”
From Microglial inhibition alleviates alpha-synuclein propagation and neurodegeneration in Parkinson’s disease mouse model (2024) · cites this paper as [23]
Minocycline molecular changes explain increased striatal dopamine levels and cognitive and locomotor improvements in zebrafish, mouse, and rat models.
“Of note, these molecular changes seem to explain the increased striatal dopamine levels as well as the cognitive and locomotor improvements observed in zebrafish, mouse, and rat models [259,260,264,268,269,270,271].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [259]
Minocycline suppresses microglia activation.
“This effect is mainly ascribable to the minocycline-dependent suppression of microglia activation, which has been reported by several in vivo studies [251,258,259,260,261,262,263].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [259]
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- Authors
- Wang, Y., Wang, Q., Yu, R., Zhang, Q., Zhang, Z., Li, H., Ren, C., Yang, R., & Niu, H.
- Affiliations
- First Affiliated Hospital of Soochow University (CN)
- Xuzhou Medical College (CN)
- Qingdao University (CN)
- Corresponding author
- Yang, Rongli
- Niu, Haichen
- Venue
- Aging
- Publisher
- Impact Journals, LLC
- Published
- 2020-07-24
- Volume
- 12
- Issue
- 14
- Pages
- 14232-14243
- ISSN
- 1945-4589 (ISSN-L)
- PMC
- PMC7425448
- OpenAlex
- W3045119216
- Cited by
- 17
- References
- 29
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2022: 4 · 2021: 1 · 2020: 1
- FWCI
- 0.65
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by
- Locations
- Aging (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- minocycline, microglial activation, Parkinson's disease, nigrostriatal dopaminergic neurons, substantia nigra, neuroinflammation, IL1R1, motor impairment, striatal dopamine, Lewy bodies, alpha-synuclein phosphorylation, neuroprotection
- MeSH terms
- Animals, Behavior, Animal, Corpus Striatum, Dopamine, Humans, Male, Mice, Inbred C57BL, Minocycline, Motor Activity, Mutation, Nerve Degeneration, Parkinson Disease, Substantia Nigra, Lewy Bodies, Microglia, Mice, alpha-Synuclein, Receptors, Interleukin-1 Type I, Dopaminergic Neurons
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