Is the spinal cord motoneuron exclusively a  target in ALS? Comparison between astroglial  reactivity in a rat model of familial ALS and in  human sporadic ALS cases.
OBJECTIVE
Motoneurons are the focus of most investigations of amyotrophic lateral sclerosis (ALS), while the astrocyte reaction is regarded as a phenomenon secondary to neuron degeneration. Since astroglial reactivity differed in different studies of human and animal ALS models and often varied from case to case, we examined and compared astrocyte reactivity within the anterior horns of the spinal cord in a transgenic rat model of familial ALS and in human sporadic ALS (sALS) cases.


METHODS
Routine histological staining and immunohistochemical reactions to cytoskeletal proteins [neurofilaments, glial fibrillary acidic protein (GFAP), vimentin and tau] and proliferative markers (proliferating cell nuclear antigen and Ki-67).


RESULTS
In human sALS cases and in rats at the early pre-symptomatic and symptomatic stages of the disease, the astroglial reaction was very weak, although there was visible evidence of the morphological manifestations of motoneuron degeneration. Poor immunoreactivity to the GFAP and vimentin antigens and increased expression of tau protein were observed in astrocytes, particularly in the rat model. The astrocyte reaction was evident during a short ‘transient’ phase of the disease in animals, between the asymptomatic and paretic stages. Proliferating cell nuclear antigen immunoreactivity in glial and neuronal nuclei was observed only in animal material.


CONCLUSIONS
Abnormalities in astrocyte cytoskeletal proteins are characteristic features for ALS, both in acquired and congenital forms of the disease. The cytoskeletal aberrations may lead to astroglial dysfunction and disturbances in glutamate uptake that may in turn increase the degeneration of motoneurons.
Rafalowska
Janina
J
Department of Experimental and Clinical Neuropathology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
Dziewulska
Dorota
D
Gadamski
Roman
R
Chrzanowska
Hanna
H
Modrzewska-Lewczuk
Malgorzata
M
Grieb
Pawel
P
D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D008875:Middle Aged; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D016900:Neurofilament Proteins / Q000378:metabolism; D051381:Rats; D055647:Rats, Transgenic; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology
D016900:Neurofilament Proteins