Role of Astrocytes in Brain Physiology and Neurologic Disease
Astrocytes are the most abundant non-neuronal cells in the central nervous system (CNS), actively modulating various brain physiology and significantly influencing the progression of certain neurological diseases. My lab is currently focusing on the astroglial glutamate transporter (EAAT2/GLT1) regulation, molecular mechanisms of neuron and astrocyte interaction in both ways, and how this interaction is altered in neurodegenerative diseases/neural injuries, such as motor neuron disease amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, Parkinson’s disease, and Epilepsy. Research in my lab will provide novel knowledge about the EAAT2/GLT1 regulation and unveil the mechanisms for the pathological alterations of neuron and astrocyte interaction in neurological disease and development of potential neuroprotective strategies for these diseases/injuries.
Neuronal regulation of astrocyte maturation and function
Despite the importance of the astrocytes in the CNS, how they become developmentally mature, especially the maturation of their unique morphology and interaction with synapses/vasculatures and induction of astroglial specific functional genes, has remained largely unknown. My lab is interested in the molecular mechanisms how astrocytes become mature postnatally, especially the role of neuronal signals in astrocyte maturation. Various genetic, imaging, and biochemical approaches will be used in both in vitro primary astrocyte and neuronal cultures and in vivo genetically modified mice. Potential abnormality of astrocyte maturation in rodent model (FMRP knock-out mice) of Fragile X Syndrome (FAS) will be also investigated.
Figure 1. Molecular and morphological maturation of astrocytes during postnatal development.
Regulation of Functional Expression of Astroglial Glutamate Transporter EAAT2/GLT1
Astroglial excitatory amino acid transporter 2 (EAAT2, rodent analog GLT1) is one of the most enriched brain proteins, playing a critical and irreplaceable role in safeguarding extracellular glutamate levels in the mammalian CNS. Low levels of extracellular glutamate greatly facilitate the proper signal transmission at synapses and prevent glutamate-induced excitotoxicity. Expression of EAAT2/GLT1 is highly dynamic under different conditions, however, the regulation mechanisms of EAAT2/GLT1 is largely unknown. My lab is interested in neuron-dependent regulation of astroglial EAAT2/GLT1 expression and the mechanisms of selective expression of EAAT2/GLT1 in astrocytes. Molecular/genetic and imaging approaches will be used in both in vitro primary astrocyte and neuronal cultures and in vivo genetically modified mice.
Figure 2. Mechanisms of neuron-dependent expression of EAAT2GLT1 in astrocytes.
Mechanisms of Astrocyte Dysfunction in Neurodegenerative Diseases
Astrocyte dysfunction has been implicated in multiple neurodegenerative disease/injury conditions. In pathological conditions, astrocytes not only lose many important functions but also gain toxicity. It is unclear whether astrocytes can play a primary role in neurological dieases, and the molecular changes of the astrocytes in disease conditions have not been investigated. My lab is interested the molecular changes of astrocyte in various neurological disease conditions, and the alterations of normal neuron to astrocyte communication in pathological conditions. Rodent models of motor neuron disease, Alzheimer’s disease, Parkinson’s disease, and Epilepsy will be used.
Figure 3. Selective isolation of in vivo astrocytes in different pathological conditions by FACS.