Absence of retinoids can induce motoneuron disease in the adult rat and a retinoid defect is present in motoneuron disease patients.
We generated retinoid-deficient adult rats by the removal of retinoids from their diet. We show that their motoneurons undergo neurodegeneration and that there is an accumulation of neurofilaments and an increase in astrocytosis, which is associated with motoneuron disease. These effects are mediated through the retinoic acid receptor alpha. The same receptor deficit is found in motoneurons from patients suffering from spontaneous amyotrophic lateral sclerosis. Furthermore, we show that there is a loss of expression of the retinaldehyde dehydrogenase enzyme II in motoneurons. Therefore, we propose that a defect in the retinoid signalling pathway is in part be responsible for some types of motoneuron disease.
Corcoran
Jonathan
J
MRC Centre for Developmental Neurobiology, New Hunt's House, King's College London, Guy's Campus, London SE1 1UL, UK. jonathan.corcoran@kcl.ac.uk
So
Po Lin
PL
Maden
Malcolm
M
D000445:Aldehyde Oxidoreductases / Q000235:genetics; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003677:Deficiency Diseases / Q000150:complications*; D006801:Humans; D017403:In Situ Hybridization; D016472:Motor Neuron Disease / Q000209:etiology*; D051381:Rats; D017208:Rats, Wistar; D018168:Receptors, Retinoic Acid / Q000235:genetics; D050697:Retinal Dehydrogenase; D012176:Retinoids / Q000172:deficiency* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
D018168:Receptors, Retinoic Acid; D012176:Retinoids; D000445:Aldehyde Oxidoreductases; D050697:Retinal Dehydrogenase