Ganglioside accumulation in activated glia in the developing brain: comparison between WT and GalNAcT KO mice

Ethanol-Induced Neurodegeneration and Glial Activation in the Developing Brain

“…The acute neuronal death induced by P7 ethanol is mitochondria-mediated apoptosis, involving Bax activation, cytochrome c release, and caspase-3 activation, which occurs 6–8 h after ethanol exposure; this is followed by neurodegeneration detected by amino cupric silver or Fluoro-Jade stain around 16–24 h [ 11 , 31 , 117 ]. Our immunohistochemical studies indicate that subcutaneous injection of ethanol in P7 mice (2.5 g/kg, 2 h apart, twice) induces not only neurodegeneration in various brain regions as described above but also activation of microglia judged by their morphology [ 17 , 18 , 19 ]. Microglia change their shapes from the resting (a small cell body and long branches) to partially activated state (bigger cell body and thicker branches), detected by Iba1 (ionized calcium-binding adapter molecule 1, specific to microglia and macrophages) immunostaining within 4 h after the first ethanol injection, and then change to rod- or amoeba-like shapes within 24 h [ 17 , 19 ].…”

“…Our immunohistochemical studies indicate that subcutaneous injection of ethanol in P7 mice (2.5 g/kg, 2 h apart, twice) induces not only neurodegeneration in various brain regions as described above but also activation of microglia judged by their morphology [ 17 , 18 , 19 ]. Microglia change their shapes from the resting (a small cell body and long branches) to partially activated state (bigger cell body and thicker branches), detected by Iba1 (ionized calcium-binding adapter molecule 1, specific to microglia and macrophages) immunostaining within 4 h after the first ethanol injection, and then change to rod- or amoeba-like shapes within 24 h [ 17 , 19 ]. These activated microglia are localized in the same area where apoptotic neurodegeneration is detected by Fluoro-Jade stain, such as in layers IV/V of the cortex, and Fluoro-Jade stain is frequently observed in Iba1-positive microglia [ 19 ].…”

“…Microglia change their shapes from the resting (a small cell body and long branches) to partially activated state (bigger cell body and thicker branches), detected by Iba1 (ionized calcium-binding adapter molecule 1, specific to microglia and macrophages) immunostaining within 4 h after the first ethanol injection, and then change to rod- or amoeba-like shapes within 24 h [ 17 , 19 ]. These activated microglia are localized in the same area where apoptotic neurodegeneration is detected by Fluoro-Jade stain, such as in layers IV/V of the cortex, and Fluoro-Jade stain is frequently observed in Iba1-positive microglia [ 19 ]. In addition, the rod- or amoeba-shaped microglia are strongly labeled with antibody against CD68, a marker for phagocytes [ 19 ], and these microglia are labeled with antibody against cleaved tau (tau cleaved by activated caspase-3) present in degenerating neurons [ 17 ], suggesting that these microglia are phagocytes engulfing degenerating neurons.…”

“…For instance, binge-like ethanol exposure in early postnatal rodents during the period equivalent to the third trimester of human pregnancy induces robust neurodegeneration [ 7 , 8 , 9 , 10 , 11 ], because neurons are particularly vulnerable to environmental toxins during this period of heightened synaptogenesis [ 12 ]. This ethanol-induced neurodegeneration, which is associated with glial activation [ 13 , 14 , 15 , 16 , 17 , 18 , 19 ] and elevation of pro- and anti-inflammatory cytokines [ 13 , 20 , 21 , 22 , 23 ], may result in long-lasting cellular, physiological, and neurobehavioral deficits [ 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. It is conceivable that ethanol-induced glial activation/neuroinflammation in animal models of FASD is involved in the long-lasting brain damage, as reported in various neurodegenerative diseases [ 33 ] and brain injuries [ 34 ].…”

Ganglioside Synthase Knockout Reduces Prion Disease Incubation Time in Mouse Models

“…Indeed, ethanol-induced astroglial activation is attenuated in GD2/GM2 KO mice. 44 Further studies will be required to examine whether the shortened incubation time in GD2/GM2 KO mice relates to the attenuated microglial reaction, including neuroprotective microglia. 45,46 In conclusion, we have shown that the ablation of GD2/ GM2 synthase gene causes a significant reduction in incubation time of prion infection.…”