I find it striking that Aβ-induced intracellular calcium waves occurred within minutes in cultured astrocytes, yet these transient waves were associated with effects on GFAP and S100B protein expression many hours later. I wonder if there are even more protracted effects in the authors' system that are "set up" by low (micromolar) levels of Aβ. Seminal work over two decades ago by Mark Mattson demonstrated that Aβ increases intracellular Ca2+ levels and leads to excitotoxicity. Is it possible that these fast and transient Ca2+ waves set into motion a series of downstream events culminating in astrocyte death?
The authors focused on Aβ1-40 in the low micromolar range in this study. It would be interesting if Aβ1-42, widely regarded as the more neurotoxic species, produces similar results, especially in oligomeric preparations.
I'd also like to comment on a point that the authors raised in their discussion section. They pointed out that any effects on AD pathophysiology are yet to be confirmed in vivo. In regard to the S100B portion of their study, we have recently shown that forced expression of human S100B, driven by the endogenous mouse S100B promoter, leads to exacerbated AD-like pathology, including gliosis and cerebral amyloidosis, in Tg2576 mice (Mori et al., 2010). When taken together with the present study, the possibility arises that these Aβ-induced perturbations in Ca2+ network signaling may exacerbate AD pathogenesis.
References:
Mori T, Koyama N, Arendash GW, Horikoshi-Sakuraba Y, Tan J, Town T.
Overexpression of human S100B exacerbates cerebral amyloidosis and gliosis in the Tg2576 mouse model of Alzheimer's disease.
Glia. 2010 Feb;58(3):300-14.
PubMed.
Comments
University of Southern California
I find it striking that Aβ-induced intracellular calcium waves occurred within minutes in cultured astrocytes, yet these transient waves were associated with effects on GFAP and S100B protein expression many hours later. I wonder if there are even more protracted effects in the authors' system that are "set up" by low (micromolar) levels of Aβ. Seminal work over two decades ago by Mark Mattson demonstrated that Aβ increases intracellular Ca2+ levels and leads to excitotoxicity. Is it possible that these fast and transient Ca2+ waves set into motion a series of downstream events culminating in astrocyte death?
The authors focused on Aβ1-40 in the low micromolar range in this study. It would be interesting if Aβ1-42, widely regarded as the more neurotoxic species, produces similar results, especially in oligomeric preparations.
I'd also like to comment on a point that the authors raised in their discussion section. They pointed out that any effects on AD pathophysiology are yet to be confirmed in vivo. In regard to the S100B portion of their study, we have recently shown that forced expression of human S100B, driven by the endogenous mouse S100B promoter, leads to exacerbated AD-like pathology, including gliosis and cerebral amyloidosis, in Tg2576 mice (Mori et al., 2010). When taken together with the present study, the possibility arises that these Aβ-induced perturbations in Ca2+ network signaling may exacerbate AD pathogenesis.
References:
Mori T, Koyama N, Arendash GW, Horikoshi-Sakuraba Y, Tan J, Town T. Overexpression of human S100B exacerbates cerebral amyloidosis and gliosis in the Tg2576 mouse model of Alzheimer's disease. Glia. 2010 Feb;58(3):300-14. PubMed.
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