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Title:
Glucocorticoid stress, neurotrophin, and pathogenesis of psychiatric disorders

Tadahiro Numakawa
Section Chief,
Department of Mental Disorder Research,
National Institute of Neuroscience ,
National Center of Neurology and Psychiatry

Abstract:
In addition to genetic background, a variety of environmental factor is speculated to be involved in the onset of psychiatric disorders such as depression. Especially, it is possible that increased glucocorticoids due to dysfunction of the hypothalamus-pituitary-adrenal axis contribute to the pathophysiology of depression. On the other hand, brain-derived neurotrophic factor (BDNF), a critical regulator for neuronal survival and plasticity in the central nervous system (CNS), is also associated with the depression. However, there is very few information on the functional interaction of BDNF with glucocorticoids. We recently found that function of BDNF in the synaptic maturation and neurotransmission was inhibited under glucocorticoid stress. Here, I would like to show possible mechanisms underlying inhibitory influence of glucocorticoids on the BDNF action. Furthermore, we recently observed negative impact achieved by phencyclidine (useful to make schizophrenia models in rodents) on secretion and/or production of BDNF in the CNS neurons. I would like to demonstrate a hypothesis for the decrease in the expression of BDNF as many studies have reported significant downregulation of BDNF in brain tissue from patient with psychiatric illness, in addition to neurodegenerative diseases.

References:
Neuroscience 239:157-172, 2013

Cereb Cortex 23:847-858, 2013

Prog. Neuropsychopharmacol. Biol. Psychiatry 39:112-119, 2012

FEBS Lett. 585:3224-3228, 2011

Proc. Natl. Acad. Sci. USA 106: 647-652, 2009

Mol. Endocrinol. 22: 546-558, 2008