Selective ablation of proliferating astrocytes does not affect disease outcome in either acute or chronic models of motor neuron degeneration.
Astrocytes play important roles in normal CNS function; however, following traumatic injury or during neurodegeneration, astrocytes undergo changes in morphology, gene expression and cellular function known as reactive astrogliosis, a process that may also include cell proliferation. At present, the role of astrocyte proliferation is not understood in disease etiology of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), a fatal motor neuron disorder that is characterized by a relatively rapid degeneration of upper and lower motor neurons. Therefore, the role of astrocyte proliferation was assessed in both acute and chronic mouse models of motor neuron degeneration, neuroadapted sindbis virus (NSV)-infected mice and SOD1(G93A) mice, respectively. While astrocytes proliferated in the lumbar spinal cord ventral horn of both disease models, they represented only a small percentage of the dividing population in the SOD1(G93A) spinal cord. Furthermore, selective ablation of proliferating GFAP(+) astrocytes in 1) NSV-infected transgenic mice in which herpes simplex virus-thymidine kinase is expressed in GFAP(+) cells (GFAP-TK) and in 2) SOD1(G93A)xGFAP-TK mice did not affect any measures of disease outcome such as animal survival, disease onset, disease duration, hindlimb motor function or motor neuron loss. Ablation of dividing astrocytes also did not alter overall astrogliosis in either model. This was likely due to the finding that proliferation of NG2(+) glial progenitors were unaffected. These findings demonstrate that while normal astrocyte function is an important factor in the etiology of motor neuron diseases such as ALS, astrocyte proliferation itself does not play a significant role.
Lepore
Angelo C
AC
Department of Neurology, The Johns Hopkins University School of Medicine, 600 North Wolfe Street, Meyer 6-119, Baltimore, MD 21287, USA.
Dejea
Christine
C
Carmen
Jessica
J
Rauck
Britta
B
Kerr
Douglas A
DA
Sofroniew
Michael V
MV
Maragakis
Nicholas J
NJ
D000208:Acute Disease; D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000473:pathology / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000166:cytology* / Q000473:pathology / Q000502:physiology; D009410:Nerve Degeneration / Q000235:genetics / Q000473:pathology*