Astrocyte Overgrowth in the Brain Stem and Spinal Cord of Mice Affected by Spinal Atrophy, Wobbler

Abstract

Biochemical and immunohistochemical analyses of the central nervous system (CNS) have been performed on the wobbler (WR) mouse, a mutant affected by a spinal atrophy. Total polypeptide patterns as well as specific neuronal and glial marker proteins were analyzed, using 2-dimensional gel electrophoresis, immunoblotting and ELISA, and the determination of enzyme activities. Despite the loss of motoneurons, the specific activities of choline acetyltransferase were not lower in WR than in control CNS samples. On the other hand, the level of glial acidic fibrillary protein (GFAP) was increased 3- to 5-fold in the spinal cord and brain stem of WR mice but not in the cerebellum. Immunohistochemistry indicated that the higher content of GFAP was due to a dense network of astrocytic processes extending over the whole cross-section of the spinal cord. This finding indicates that astrocyte overgrowth may be a fundamental feature of the wobbler disease, rather than occurring locally in response to motoneuron degeneration.

Proteomic analysis of muscle affected by motor neuron degeneration: The wobbler mouse model of amyotrophic lateral sclerosis

“…Recent proteomic profiling studies of ALS patient samples and the WR animal model have focused on the analysis of cerebrospinal fluid [19][20][21] and cervical and lumbar spinal cord [22,23], respectively. The studies on the WR mouse showed that the majority of differentially expressed proteins were related to the glutamate-glutamine cycle, energy transduction, redox functions and astrogliosis [22], thus confirming previous studies [24]. Here, we have applied comparative proteomics to the analysis of skeletal muscle from the WR mouse and established changes in proteins involved in metabolic pathways, the contractile apparatus, intermediate filaments and the cellular stress response.…”

“…Expression levels were reduced in the case of 3 protein species and increased for 21 proteins. The mass spectrometric hit with the highest increase of 6.5 relative concentration is not listed in Table 1 proteins spots which both represent fast myosin binding protein C (spots 23,24). In order to verify key proteomic findings and to put this study into perspective with previous analyses of WR muscle tissues, representative immunoblots are shown in Fig.…”

Tumor Necrosis Factor-α (TNF-α) Regulates Shedding of TNF-α Receptor 1 by the Metalloprotease-Disintegrin ADAM8: Evidence for a Protease-Regulated Feedback Loop in Neuroprotection

“…In these mice, an essential role for TNF-␣ in disease progression has been excluded by crossing TNF-␣-deficient with SOD1(G93A) tg mice (Gowing et al, 2006). The minor importance of TNF-␣ in these mice might be reflected by a relatively low response of glial cells to motor neuron degeneration in the spinal cord, whereas astrogliosis and microglia activation are prominent in WR spinal cord and brainstem (Laage et al, 1988;Rathke-Hartlieb et al, 1999). Nevertheless, ADAM8 is upregulated in spinal cords of SOD1(G93A) tg under disease conditions, most likely by other proinflammatory cytokines such as IL-1␤ (U. Schlomann and J.W.B., unpublished data).…”

“…Mice were deeply anesthetized and transcardially perfused with fixative, as described previously (Laage et al, 1988) for preparation of paraffin serial sections of spinal cords. For motor neuron counts, cryosections (10 m) and paraffin sections from spinal cords were serially cut (5 m), and every 10th section was processed by counting motor neuron numbers in the ventrolateral motor neuron pool.…”

Zonisamide Treatment Delays Motor Neuron Degeneration and Astrocyte Proliferation in Wobbler Mice

“…Spinal cord GFAP levels were increased in wobbler mice at aged 2 months. Immunohistochemical studies suggested astrocyte overgrowth in the cervical cord of wobbler mice at the age of 2-3 months [21,22]. Astrocytes derived from wobbler murine neural precursor cells displayed impairment of glutamate homeostasis [23].…”