ROCK/Cdc42-mediated microglial motility and gliapse formation lead to phagocytosis of degenerating dopaminergic neurons in vivo
نویسندگان
چکیده
The role of microglial motility in the context of adult neurodegeneration is poorly understood. In the present work, we investigated the microanatomical details of microglia-neuron interactions in an experimental mouse model of Parkinson's disease following the intraperitoneal injection of MPTP. The specific intoxication of dopaminergic neurons induces the cellular polarization of microglia, leading to the formation of body-to-body neuron-glia contacts, called gliapses, which precede neuron elimination. Inhibiting ROCK/Cdc42-mediated microglial motility in vivo blocks the activating features of microglia, such as increased cell size and number of filopodia and diminishes their phagocyting/secreting domains, as the reduction of the Golgi apparatus and the number of microglia-neuron contacts has shown. High-resolution confocal images and three-dimensional rendering demonstrate that microglia engulf entire neurons at one-to-one ratio, and the microglial cell body participates in the formation of the phagocytic cup, engulfing and eliminating neurons in areas of dopaminergic degeneration in adult mammals.
منابع مشابه
P185: Survey Effect of Histamine on Microglia in Neurodegenerative Diseases
Neurodegenerative diseases contain Multiple Sclerosis (MS), Alzheimer’s disease (AD) and Parkinson’s disease (PD), are characterized by neuronal death and neuronal degeneration in specific regions of the central nervous system (CNS). Microglia are the basic immune brain cells and play a role in homeostasis after inflammation challenge. Microglia involves in Neurodegenerative disease...
متن کاملRotenone induces neuronal death by microglial phagocytosis of neurons.
Rotenone, a common pesticide and inhibitor of mitochondrial complex I, induces microglial activation and loss of dopaminergic neurons in models of Parkinson's disease. However, the mechanisms of rotenone neurotoxicity are still poorly defined. Here, we used primary neuronal/glial cultures prepared from rat cerebella to investigate the contribution of microglia to neuronal cell death induced by ...
متن کاملPathological histone acetylation in Parkinson’s disease: Neuroprotection and inhibition of microglial activation through SIRT 2 inhibition
Parkinson's disease (PD) is associated with degeneration of nigrostriatal neurons due to intracytoplasmic inclusions composed predominantly of a synaptic protein called α-synuclein. Accumulations of α-synuclein are thought to 'mask' acetylation sites on histone proteins, inhibiting the action of histone acetyltransferase (HAT) enzymes in their equilibrium with histone deacetylases (HDACs), thus...
متن کاملDegeneration in vivo of rat hippocampal neurons by wild-type Alzheimer amyloid precursor protein overexpressed by adenovirus-mediated gene transfer.
In an attempt to elucidate the pathological implications of intracellular accumulation of the amyloid precursor protein (APP) in postmitotic neurons in vivo, we transferred APP695 cDNA into rat hippocampal neurons by using a replication-defective adenovirus vector. We first improved the efficiency of adenovirus-mediated gene transfer into neurons in vivo by using hypertonic mannitol. When a bet...
متن کاملNen20553 1092..1102
In both Parkinson disease and in animal models of Parkinson disease, there is a microglial reaction in addition to the loss of dopaminergic neurons in the ventral midbrain. To determine the pathological role of this microglial reaction, we analyzed the kinetics of microglial activation and dopaminergic cell death induced in rats with the neurotoxin 6-hydroxydopamine. As early as Day 1 after the...
متن کامل