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Publication : BDNF heterozygous mice demonstrate age-related changes in striatal and nigral gene expression.

First Author  Saylor AJ Year  2006
Journal  Exp Neurol Volume  199
Issue  2 Pages  362-72
PubMed ID  16478623 Mgi Jnum  J:111309
Mgi Id  MGI:3653580 Doi  10.1016/j.expneurol.2006.01.004
Citation  Saylor AJ, et al. (2006) BDNF heterozygous mice demonstrate age-related changes in striatal and nigral gene expression. Exp Neurol 199(2):362-72
abstractText  TrkB receptors mediate the effects of BDNF on striatal medium spiny neurons and mesencephalic dopamine neurons. The effect of partial BDNF gene deletion on locomotor activity and the gene expression of these neurons was evaluated at 3, 12, and 24 months of age in BDNF heterozygous (BDNF(LacZ/neo+)) and wildtype mice. BDNF(LacZ/neo+) mice displayed less spontaneous horizontal activity than wildtypes at 3 and 24 months of age. Whereas striatal preproenkephalin and preprodynorphin mRNA and mesencephalic tyrosine hydroxylase mRNA levels were significantly lower at all ages in BDNF(LacZ/neo+) mice, GAD67 mRNA was only lower at 24 months. In contrast, BDNF(LacZ/neo+) mice expressed more trkB mRNA in the striatum at 3 months and less at 24 months of age than wildtypes. Total striatal cell number in the two genotypes was not different at 12 months of age, whereas Golgi staining revealed that the spine density on distal dendrites of medium spiny neurons was less in BDNF(LacZ/neo+) mice than in wildtypes at 24 months of age. These data indicate that endogenous BDNF is required to maintain the normal phenotype and functioning of striatal projection neurons and mesencephalic dopamine neurons and that exaggerated dysfunction of these neurons and a concomitant decline in locomotor behavior occurs during aging.
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