Abstract
BackgroundThe acupuncture or electroacupuncture (EA) shows the therapeutic effect on various neurodegenerative diseases. This effect was thought to be partially achieved by its ability to alleviate existing neuroinflammation and glial dysfunction. In this study, we systematically investigated the effect of EA on abnormal neurochemical changes and motor symptoms in a mouse neurodegenerative disease model.MethodsThe transgenic mouse which expresses a mutant α-synuclein (α-syn) protein, A53T α-syn, in brain astrocytic cells was used. These mice exhibit extensive neuroinflammatory and motor phenotypes of neurodegenerative disorders. In this study, the effects of EA on these phenotypic changes were examined in these mice.ResultsEA improved the movement detected in multiple motor tests in A53T mutant mice. At the cellular level, EA significantly reduced the activation of microglia and prevented the loss of dopaminergic neurons in the midbrain and motor neurons in the spinal cord. At the molecular level, EA suppressed the abnormal elevation of proinflammatory factors (tumor necrosis factor-α and interleukin-1β) in the striatum and midbrain of A53T mice. In contrast, EA increased striatal and midbrain expression of a transcription factor, nuclear factor E2-related factor 2, and its downstream antioxidants (heme oxygenase-1 and glutamate-cysteine ligase modifier subunits).ConclusionsThese results suggest that EA possesses the ability to ameliorate mutant α-syn-induced motor abnormalities. This ability may be due to that EA enhances both anti-inflammatory and antioxidant activities and suppresses aberrant glial activation in the diseased sites of brains.
Highlights
The acupuncture or electroacupuncture (EA) shows the therapeutic effect on various neurodegenerative diseases
EA delayed the early onset of movement disability in A53T mice A53T α-syn mice were administered with DOX from embryonic stages (E0) to postnatal day 21 (P21) to block the developmental expression of A53T α-syn (Fig. 1a)
The early-onset paralysis was seen in A53T mice which may result from the significant neuronal loss in the midbrain and spinal cord [15]
Summary
The acupuncture or electroacupuncture (EA) shows the therapeutic effect on various neurodegenerative diseases This effect was thought to be partially achieved by its ability to alleviate existing neuroinflammation and glial dysfunction. As a conventional cytosolic protein, α-synuclein (α-syn), has been assumed to exert its pathogenic function exclusively in the cytoplasm in a cell-autonomous manner [1]. This view has been challenged by the presence of α-syn and its aggregated forms in the extracellular fluid such as cerebrospinal fluid and blood plasma of both Parkinson’s disease (PD) and normal subjects [2, 3]. The underlying mechanisms for α-synucleinopathies in glia and its roles in disease onset and progression remain unclear
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