Koji Yamanaka & Don W.
Cleveland talk with ScienceWatch.com and answer a
few questions about this month's Fast Breaking Paper in the
field of Neuroscience & Behavior. The authors have also
sent along images of their work.
Article Title: Astrocytes as determinants of
disease progression in inherited amyotrophic lateral
sclerosis
Authors: Yamanaka,
K;Chun, SJ;Boillee, S;Fujimori-Tonou, N;Yamashita,
H;Gutmann, DH;Takahashi, R;Misawa,
H;Cleveland,
DW
Figure 1:
Fluorescence staining of lumbar spinal cord
section from symptomatic mutant SOD1 mouse.
Prominent activation of microglia
(anti-Mac2: red), and astrocytes
(anti-GFAP: green) are detected. Neurons
and their process stained with SMI-32
(non-phosphorylated neurofilament: blue).
Figure 2:
Figure 2:
Accelerated disease progression from mutant
SOD1-mediated toxicity within astrocytes
and microglia driving non-cell-autonomous
motor neuron death. Initial damage within
motor neurons including age dependent
accumulation of an as yet unidentified
mutant SOD1-mediated toxicity. Unidentified
factors derived from damaged motor neurons
or astrocytes cause activation of
mutant-expressing microglia. Abnormal
activated microglia produce high levels of
nitric oxide and superoxide together with
secretion of toxic cytokines to motor
neurons. A combination of damage from
mutant microglia and astrocytes cause
further damage to motor neurons, thereby
driving rapid disease progression.