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Doublecortin (DCX)-positive neural precursor cells (NPCs) comprise a significant phagocytic population within the neurogenic zones during adult neurogenesis,and their phagocytic activity critically contributes to neurogenesis in the adult brain.Ingestion of apoptotic cells increases the activity of AMP-activated protein kinase (AMPK),a serine/threonine protein kinase that acts as an energy sensor and is rapidly activated after phagocytosis as a key regulator involved in sensing cellular ATP levels.Gamma-aminobutyric acid (GABA),the major inhibitory neurotransmitter in the adult brain,initially exerts an excitatory action on newborn neurons due to their high cytoplasmic chloride content.GABAb receptors are intimately associated with AMPK.GABAb receptors are heterodimeric,G-protein-coupled receptors composed of R1 and R2 subunits that mediate slow synaptic inhibition in the brain by activating inwardly-rectifying K* channels (GIRKs) and inhibiting Ca2* channels.They can also function as an important synaptic maturation signal early in life.AMPK is phosphorylated on threonine 172 (T172) by enhanced metabolic activity,binds to the R1 subunit,and directly phosphorylates S783 in the R2 submit of the GABAB receptor to enhance its activation of GIRKs.The activation of GABAb receptors triggers the secretion of brain-derived neurotrophic factor (BDNF) and promotes the functional maturation of GABAergic synapses in the hippocampus.To elucidate the molecular mechanisms controlling how NPCs phagocytosis affects adult-born neuronal plasticity,we chose AMPK and GABA receptors and detected their role during micratubule development and membrane receptor subunit metabolisms on newborn neurons.NPCs from adult-born C57BL76J mice were cultured in vitro and treated with annexin V,which blocks the uptake of apoptotic cells by DCX* cells.The phosphorylation of AMPK was measured by immunofluorescence of phospho-AMPKa (Thr172).GABA receptor membrane expression was detected by immunohistochemistry.Neuronal microtubules were labeled with β-III tubulin using immunofluorescence.The results showed that the phosphorylation of AMPK and expression of GABA receptors were decreased after blocking phagocytosis.The expansion of microtubules was inhibited by the application of annexin V.Next,we treated the NPCs with 1 mmol/L AICAR (an AMPK activator) and/or 10 μmol/L compound C (an AMPK inhibitor).The phagocytic ability of DCX* NPCs was measured by their engulfment of 3 μm fluorescent microspheres.Our results showed that the number of fluorescent beads engulfed by DCX* NPCs was increased with the administration of AICAR and decreased by the inhibition of AMPK.The activation of AMPK promoted the phosphorylation of GABA receptors and their expression on the membrane as measured by immunofluorescence.The fluorescence intensity of BDNF was also enhanced by AMPK activation.Confocal images demonstrated that cells cultured with AICAR exhibited morphological and physiological changes,including increased cell size and the ability to engulf beads.Annexin V was intravenously injected at a dose of 5 μg per 100 μL in vivo.Neuron development was detected by the length of dendrites and the number of dendrite spines of DCX* cells.The number of newborn neurons was detected by the amount of DCX*/BrdlT cells using immunohistochemistry.Our data indicated that injection of annexin V altered the development of newborn neurons by decreasing the number of DCX*/BrdU* cells and reducing the thickness of the granular cell layer of the hippocampus.These findings showed that the phagocytic activity of neuronal progenitors can clearly enhance the development of newborn neurons and that the phosphorylation of AMPK can promote the modulation of GABA receptors on the membrane,changing GABAergic synapses and the distribution of microtubules,which played an important role in adult-bom neuron neurogenesis and plasticity.