Glucocorticoid affects dendritic transport of BDNF-containing vesicles

Naoki Adachi; Tadahiro Numakawa; Shingo Nakajima; Masashi Fukuoka; Haruki Odaka; Yusuke Katanuma; Yoshiko Ooshima; Hirohiko Hohjoh; Hiroshi Kunugi

doi:10.1038/srep12684

Glucocorticoid affects dendritic transport of BDNF-containing vesicles

Sci Rep. 2015 Aug 4:5:12684. doi: 10.1038/srep12684.

Authors

Naoki Adachi¹, Tadahiro Numakawa², Shingo Nakajima³, Masashi Fukuoka⁴, Haruki Odaka⁵, Yusuke Katanuma⁵, Yoshiko Ooshima⁶, Hirohiko Hohjoh⁴, Hiroshi Kunugi⁷

Affiliations

¹ 1] Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan [2] Core Research for Evolutional Science and Technology Program (CREST), Japan Science and Technology Agency (JST), Saitama, Japan [3] Department of Biomedical Chemistry, Kwansei Gakuin University, Sanda, Japan.
² 1] Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan [2] Core Research for Evolutional Science and Technology Program (CREST), Japan Science and Technology Agency (JST), Saitama, Japan [3] Department of Cell Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
³ 1] Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan [2] Faculty of Health Science, Hokkaido University, Sapporo, Japan.
⁴ Department of Molecular Pharmacology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
⁵ 1] Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan [2] Department of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.
⁶ 1] Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan [2] Department of Molecular Pharmacology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
⁷ 1] Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan [2] Core Research for Evolutional Science and Technology Program (CREST), Japan Science and Technology Agency (JST), Saitama, Japan.

Abstract

Brain-derived neurotrophic factor (BDNF) is essential for neuronal survival, differentiation, and functions in the central nervous system (CNS). Because BDNF protein is sorted into secretory vesicles at the trans-Golgi network in the cell body after translation, transport of BDNF-containing vesicles to the secretion sites is an important process for its function. Here we examined the effect of dexamethasone (DEX), a synthetic glucocorticoid, on BDNF-containing vesicle transport and found that DEX decreased the proportion of stationary vesicles and increased velocity of the microtubule-based vesicle transport in dendrites of cortical neurons. Furthermore, DEX increased huntingtin (Htt) protein levels via glucocorticoid receptor (GR) activation, and reduction in the amount of Htt by a specific shRNA reversed the action of DEX on BDNF vesicle transport. Given that Htt protein is a positive regulator for the microtubule-dependent vesicular transport in neurons, our data suggest that glucocorticoid stimulates BDNF vesicle transport through upregulation of Htt protein levels.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Animals, Newborn
Biological Transport
Brain-Derived Neurotrophic Factor / genetics*
Brain-Derived Neurotrophic Factor / metabolism
Cerebral Cortex / cytology
Cerebral Cortex / drug effects
Cerebral Cortex / metabolism
Dexamethasone / pharmacology*
Gene Expression Regulation
Glucocorticoids / pharmacology*
Huntingtin Protein
Microtubules / drug effects
Microtubules / metabolism
Nerve Tissue Proteins / antagonists & inhibitors
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / metabolism
Neurons / drug effects*
Neurons / metabolism
Neurons / ultrastructure
Nuclear Proteins / antagonists & inhibitors
Nuclear Proteins / genetics
Nuclear Proteins / metabolism
Primary Cell Culture
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
Rats
Rats, Wistar
Receptors, Glucocorticoid / genetics
Receptors, Glucocorticoid / metabolism
Synapses / drug effects
Synapses / metabolism
Synaptic Transmission
Transport Vesicles / drug effects*
Transport Vesicles / metabolism
trans-Golgi Network / drug effects*
trans-Golgi Network / metabolism

Substances

Brain-Derived Neurotrophic Factor
Glucocorticoids
Htt protein, rat
Huntingtin Protein
Nerve Tissue Proteins
Nuclear Proteins
RNA, Small Interfering
Receptors, Glucocorticoid
Dexamethasone