TY - JOUR
T1 - Expression and p75 neurotrophin receptor dependence of cholesterol synthetic enzymes in adult mouse brain
AU - Korade, Zeljka
AU - Mi, Zhiping
AU - Portugal, Carmel
AU - Schor, Nina F.
N1 - Funding Information:
Thanks to Dr. Karoly Mirnics for the help with quantitative PCR experiments, Dr. Takanori Hashimoto for protocol for double in situ hybridization, and Melissa Macioce for preparing cryostat sections. This work is supported by Carol Ann Craumer Endowed Chair for Pediatric Research and NIH R01 NS038569 and NS041297 (NFS).
PY - 2007/10
Y1 - 2007/10
N2 - Normal brain function depends critically on cholesterol. Although cholesterol is synthesized locally in the adult brain, the precise anatomical localization of cholesterogenic enzymes is not known. Here we show that 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoAred) and 7-dehydrocholesterol reductase (7dhcred), the first and last enzymes, respectively, in the cholesterol biosynthesis pathway, are co-expressed in neurons throughout adult murine brain. Co-localization is most prominent in cortical, hippocampal, and cholinergic neurons. Since adult hippocampal and cholinoergic neurons express p75 neurotrophin receptors (p75NTR) we hypothesized that p75NTR regulates expression of cholesterogenic enzymes. Treatment of Neuro2a neuroblastoma cells or primary cerebellar cultures with siRNA downregulates p75NTR and decreases the expression level of HMG-CoAred and 7dhcred. Native neuroblastoma cell lines with differential expression of p75NTR differentially express 7dhcred; 7dhcred expression correlates with p75NTR expression. This suggests that, in p75NTR-expressing cells, p75NTR regulates cholesterol synthesis through regulation of HMG-CoAred and 7dhcred expression. The unexpected localization of cholesterogenic enzymes in adult neurons suggests that at least some adult neurons retain the ability to synthesize cholesterol.
AB - Normal brain function depends critically on cholesterol. Although cholesterol is synthesized locally in the adult brain, the precise anatomical localization of cholesterogenic enzymes is not known. Here we show that 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoAred) and 7-dehydrocholesterol reductase (7dhcred), the first and last enzymes, respectively, in the cholesterol biosynthesis pathway, are co-expressed in neurons throughout adult murine brain. Co-localization is most prominent in cortical, hippocampal, and cholinergic neurons. Since adult hippocampal and cholinoergic neurons express p75 neurotrophin receptors (p75NTR) we hypothesized that p75NTR regulates expression of cholesterogenic enzymes. Treatment of Neuro2a neuroblastoma cells or primary cerebellar cultures with siRNA downregulates p75NTR and decreases the expression level of HMG-CoAred and 7dhcred. Native neuroblastoma cell lines with differential expression of p75NTR differentially express 7dhcred; 7dhcred expression correlates with p75NTR expression. This suggests that, in p75NTR-expressing cells, p75NTR regulates cholesterol synthesis through regulation of HMG-CoAred and 7dhcred expression. The unexpected localization of cholesterogenic enzymes in adult neurons suggests that at least some adult neurons retain the ability to synthesize cholesterol.
KW - 7dhcred
KW - Cholesterol
KW - HMG-CoAred
KW - In situ hybridization
KW - P75 neurotrophin receptor
UR - http://www.scopus.com/inward/record.url?scp=34547726261&partnerID=8YFLogxK
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U2 - 10.1016/j.neurobiolaging.2006.06.026
DO - 10.1016/j.neurobiolaging.2006.06.026
M3 - Article
C2 - 16887237
AN - SCOPUS:34547726261
SN - 0197-4580
VL - 28
SP - 1522
EP - 1531
JO - Neurobiology of Aging
JF - Neurobiology of Aging
IS - 10
ER -