Ischemia-induced Neurogenesis of Neocortical Layer 1 Progenitor Cells
Nature Neuroscience VOLUME 13 | NUMBER 2 | February 2010
Speaker : 陳意涵
Date : 2010/10/04
Commentator : 許桂森 老師
Factors Modulate Neurogenesis
• Upregulate NeurogenesisExerciseEnvironmental Enrichment Pregnancy Stroke
• Downregulate NeurogenesisStress Aging
Physiol Rev 85: 523–569, 2005
Neocortical Neurogenesis
Ann Neurol 2007;61:199–208
NeuN : Neuronal nucleiDCX : doublecortin
2 weeks after H-I
5 weeks after H-I
Ki67 : cell proliferation marker
BrdU & pH3 : cell proliferation marker
GAD67 :
Nkx2.1 & MafB : ganglionic eminence
Layer 1 Ki67 and GAD67 double-positive cells might be ganglionic eminence–derived proliferating cells.
Time-course quantification
F : FrontalM : Motor S : SomatosensoryV : Visual
Left : neostriatumRight : thalamic nuclei
1.56 fold
Time course Ki67-/GAD67+/ GFP+ cells, which were produced from
layer 1 Ki67+/ GAD67+/GFP+ cells by the ischemic stimuli, migrated to the deepest layers within 7–10 d of
the ischemia treatment
TuJ1 & HuC/D : immature neuronal markerMAP2 : mature neuronal markerGFP-positive cells in layer 2–6 share the
morphological and molecular characteristics of neurons
SYN1 (synapsin 1) promoter
Few layer 2–6 GFP-positive cells were colabeled with glial marker antibodies
GFAP: astrocytesOligo : Oligodendrocytes (rat glial membrane & whole-brain white matter )CD11b : microglia
GFAP : astrocyteOligo : oligodendrocyte
Magenta : neuron marker HuC/D
New neocortical neurons may not be generated in the SVZ or white matter in these conditions
8 weeks post ischemia
NPY : neuropeptide Y ChAT : choline acetyltransferaseSOM : somatostatinCR : Calretinen
Newly generated neurons matured and/or that the newly generated immature neurons died
New neurons might be short lived
Environmental Enrichment
Nature Vol.386 493-495,3, April ,1997
1.Attenuates stress responses2.Protects rats from excessive anxiety in the face of new challenges
Barrel cortex of the primary somatosensory cortex
Control : original cage Enriched : new enriched environment
At least some of the newly generated neurons were functionally incorporated into the cortical circuit
Glial cells in the layer 3–4 of somatosensory cortex
NeuN & GAD67 : neuronsS100 β : astrocytesOligo : oligodendrocytesCD11b : microglias
Almost all c-Fos expression was confined to neurons 4 weeks after ischemia
Summary
• NPCs exist in the neocortical layer 1 of the adult rats
• The layer 1 NPCs produced GABAergicinterneurons under ischemic conditions