MYELIN BASIC PROTEIN

   A hypothesis of abnormal brain development resulting from dysfunctional myelination has been proposed as a potential etiologic factor in autism (Reiss et al, 1986).

   Cell-mediated immune response to human myelin basic protein was studied by the macrophage migration inhibition factor test in 17 autistic patients and a control group of 11 patients suffering from other mental diseases included in the differential diagnosis of the syndrome of autism. Of 17 autistic patients, 13 demonstrated inhibition of macrophage migration, whereas none of the nonautistic patients showed such a response (Weizman et al, 1982).

   The myelin genes have been found to be under thyroid hormone control (Farsetti et al, 1992).

   The abundance of the mRNAs for the major myelin proteins proteolipid protein, myelin basic protein, and  myelin-associated glycoprotein, expressed by oligodendrocytes, were decreased in hypothyroid brains (Munoz et al, 1991).

   Recent studies in cancer gene therapy  have shown that the myelin basic protein promoter (MBPp) is switched off when T3 is removed from the serum of the culture medium (Martin et al, 2000).

   Oligodendrocyte maturation - a neuroglial cell of the central nervous system in vertebrates whose function is to myelinate CNS axons - is also regulated by thyroid hormone (Baas et al, 1997).

   2',3'cyclic nucleotide phosphohydrolase (CNPase), a specific marker for oligodendrocytes and myelination was significantly decreased in all regions except the spinal cord of hypothyroid rats (Virgili et al, 1991).

Gq/11: G alpha(q/11) proteins are expressed at high levels at all stages of granulomonocytic and erythroid differentiation (Tenailleau et al,1997).

Edg-2  was the the first found G-protein-coupled receptor identified in myelin-forming cells (Allard et al, 1998).

Edg receptors are also coupled to Gq/11 (Beer, 2000).

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Allard J, Barron S, Diaz J, Lubetzki C, Zalc B, Schwartz JC, Sokoloff P - "A rat G protein-coupled receptor selectively expressed in myelin-forming cells" Eur J Neurosci 10(3):1045-53 (1998) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=9753172&form=6&db=m&Dopt=r

Baas D, Bourbeau D, Sarlieve LL, Ittel ME, Dussault JH, Puymirat J - "Oligodendrocyte maturation and progenitor cell proliferation are independently regulated by thyroid hormone" Glia 19(4):324-32 (1997) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=9097076&form=6&db=m&Dopt=r

Beer MS, Stanton JA, Salim K, Rigby M, Heavens RP, Smith D, Mcallister G - "EDG receptors as a therapeutic target in the nervous system" Ann N Y Acad Sci 905:118-31  (2000) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=10818448&form=6&db=m&Dopt=r

Farsetti A, Desvergne B, Hallenbeck P, Robbins J, Nikodem V - "Characterization of myelin basic protein thyroid hormone response element and its function in the context of native and heterologous promoter" J Biol Chem 267:15784-15788 (1992) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=1379237&form=6&db=m&Dopt=r

Martin V, Cortes ML, de Felipe P, Farsetti A, Calcaterra NB, Izquierdo M - "Cancer gene therapy by thyroid hormone-mediated expression of toxin genes" Cancer Res 60(12):3218-24 (2000) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=10866314&form=6&db=m&Dopt=r

Munoz A, Rodriguez-Pena A, Perez-Castillo A, Ferreiro B, Sutcliffe JG, Bernal J - "Effects of neonatal hypothyroidism on rat brain gene expression" Mol Endocrinol 5(2):273-80 (1991) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=1710032&form=6&db=m&Dopt=r

Reiss AL, Feinstein C, Rosenbaum KN  - "Autism and genetic disorders." Schizophr Bull 12(4):724-38 (1986) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3810072&form=6&db=m&Dopt=r

Tenailleau S, Corre I, Hermouet S - "Specific expression of heterotrimeric G proteins G12 and G16 during human myeloid differentiation" Exp Hematol 25(9):927-34 (1997) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=9257805&form=6&db=m&Dopt=r

Virgili M, Saverino O, Vaccari M, Barnabei O, Contestabile A - "Temporal, regional and cellular selectivity of neonatal alteration of the thyroid state on neurochemical maturation in the rat" Exp Brain Res 1991;83(3):555-61  (1991) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=1851100&form=6&db=m&Dopt=r

Weizman A, Weizman R, Szekely GA, Wijsenbeek H, Livni E - "Abnormal immune response to brain tissue antigen in the syndrome of autism" Am J Psychiatry 139(11):1462-5  (1982) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=6182806&form=6&db=m&Dopt=r