Activity-induced and developmental downregulation of the Nogo receptor
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Activity-induced and developmental downregulation of the Nogo receptor. / Josephson, Anna; Trifunovski, Alexandra; Schéele, Camilla; Widenfalk, Johan; Wahlestedt, Claes; Brené, Stefan; Olson, Lars; Spenger, Christian.
In: Cell and Tissue Research, Vol. 311, No. 3, 03.2003, p. 333-42.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Activity-induced and developmental downregulation of the Nogo receptor
AU - Josephson, Anna
AU - Trifunovski, Alexandra
AU - Schéele, Camilla
AU - Widenfalk, Johan
AU - Wahlestedt, Claes
AU - Brené, Stefan
AU - Olson, Lars
AU - Spenger, Christian
PY - 2003/3
Y1 - 2003/3
N2 - The three axon growth inhibitory proteins, myelin associated glycoprotein, oligodendrocyte-myelin glycoprotein and Nogo-A, can all bind to the Nogo-66 receptor (NgR). This receptor is expressed by neurons with high amounts in regions of high plasticity where Nogo expression is also high. We hypothesized that simultaneous presence of high levels of Nogo and its receptor in neurons confers a locked state to hippocampal and cortical microcircuitry and that one or both of these proteins must be effectively and temporarily downregulated to permit plastic structural changes underlying formation of long-term memory. Hence, we subjected rats to kainic acid treatment and exposed rats to running wheels and measured NgR mRNA levels by quantitative in situ hybridization at different time points. We also studied spinal cord injuries and quantified NgR mRNA levels in spinal cord and ganglia during a critical postnatal period using real-time PCR. Strikingly, kainic acid led to a strong transient downregulation of NgR mRNA levels in gyrus dentatus, hippocampus, and neocortex during a time when BDNF mRNA was upregulated instead. Animals exposed to running wheels for 3 and 7, but not 1 or 21, days showed a significant downregulation of NgR mRNA in cortex, hippocampus and the dentate gyrus. NgR mRNA levels decreased from high to low expression in spinal cord and ganglia during the first week of life. No robust regulation of NgR was observed in the spinal cord following spinal cord injury. Together, our data show that NgR levels in developing and adult neurons are regulated in vivo under different conditions. Strong, rapid and transient downregulation of NgR mRNA in response to kainic acid and after wheel running in cortex and hippocampus suggests a role for NgR and Nogo-A in plasticity, learning and memory.
AB - The three axon growth inhibitory proteins, myelin associated glycoprotein, oligodendrocyte-myelin glycoprotein and Nogo-A, can all bind to the Nogo-66 receptor (NgR). This receptor is expressed by neurons with high amounts in regions of high plasticity where Nogo expression is also high. We hypothesized that simultaneous presence of high levels of Nogo and its receptor in neurons confers a locked state to hippocampal and cortical microcircuitry and that one or both of these proteins must be effectively and temporarily downregulated to permit plastic structural changes underlying formation of long-term memory. Hence, we subjected rats to kainic acid treatment and exposed rats to running wheels and measured NgR mRNA levels by quantitative in situ hybridization at different time points. We also studied spinal cord injuries and quantified NgR mRNA levels in spinal cord and ganglia during a critical postnatal period using real-time PCR. Strikingly, kainic acid led to a strong transient downregulation of NgR mRNA levels in gyrus dentatus, hippocampus, and neocortex during a time when BDNF mRNA was upregulated instead. Animals exposed to running wheels for 3 and 7, but not 1 or 21, days showed a significant downregulation of NgR mRNA in cortex, hippocampus and the dentate gyrus. NgR mRNA levels decreased from high to low expression in spinal cord and ganglia during the first week of life. No robust regulation of NgR was observed in the spinal cord following spinal cord injury. Together, our data show that NgR levels in developing and adult neurons are regulated in vivo under different conditions. Strong, rapid and transient downregulation of NgR mRNA in response to kainic acid and after wheel running in cortex and hippocampus suggests a role for NgR and Nogo-A in plasticity, learning and memory.
KW - Animals
KW - Brain
KW - Brain-Derived Neurotrophic Factor
KW - Cerebral Cortex
KW - Disease Models, Animal
KW - Down-Regulation
KW - GPI-Linked Proteins
KW - Ganglia, Spinal
KW - Higher Nervous Activity
KW - Hippocampus
KW - Kainic Acid
KW - Learning
KW - Male
KW - Motor Activity
KW - Myelin Proteins
KW - Neuronal Plasticity
KW - Nogo Proteins
KW - Nogo Receptor 1
KW - RNA, Messenger
KW - Rats
KW - Rats, Inbred SHR
KW - Rats, Sprague-Dawley
KW - Receptors, Cell Surface
KW - Receptors, Peptide
KW - Spinal Cord
KW - Spinal Cord Injuries
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1007/s00441-002-0695-8
DO - 10.1007/s00441-002-0695-8
M3 - Journal article
C2 - 12658441
VL - 311
SP - 333
EP - 342
JO - Cell and Tissue Research
JF - Cell and Tissue Research
SN - 0302-766X
IS - 3
ER -
ID: 170177444