"Analysis of neurosteroid effects on hippocampal neural circuits using novel multi-electrode probe methods"
Bioinformatics Project about automatic spine analysis from 2006-
JST Bioinformatics Project on "Automatic Analysis of Neuronal Synapses in Brain Slices."
Spine analysis software "Spiso-3D" can be downloaded.
>>[Manual],[Full Spiso-3D]
,[Use Java32bit ->Spiso and ImageJ]
We show how "Spiso-3D" works as movie demonstration.
>>[2018 MOVIE MediaPlayer],
[2010 MOVIE MediaPlayer]
In case you wish to use this software, please contact us by the following e-mail.
E-mail : skkawato"atmark"gmail.com ("atmark"→@)
Accurate three-dimensional determination of postsynaptic structures is essential to our understanding memory-related function and pathology in neurons. However, current methods of spine analysis require time consuming and labour intensive manual spine identification in large image data sets. Therefore a realistic implementation of algorithm is necessary to replace manual identification. Here we describe a new method for the automated detection of spines and dendrites based on analysis of geometrical features. Our "Spiso-3D" software carries out automated dendrite reconstruction and spine detection using both eigenvalue images and information of brightness, avoiding detection of pseudo-spines. As a good demonstration, Spiso-3D is applied to analyze the effects of estrogen and androgen on rapid modulation of spinogenesis (e.g., change in spine head diameter) in the hippocampus. We have published many reports (see Publication of this HP).
Team Leader of CREST / JST Project from 2000-
Core Research for Evolutional Science and Technology(CREST Type),
Endocrine Disrupters Research Area,
"Endocrine Disrupters as Disrupters of Brain Function: Neurosteroid Point of View"
Our research team investigates the disruptive actions of endocrine disrupters (EDs), as well as the action of estrogen on neurotransmission in the hippocampus, the center for learning and memory. In current neuroendocrinology, it is widely believed that steroid hormones are synthesized in the gonads and / or adrenal glands, and reach the brain via the blood circulation. In contrast with this view, (A) we are in progress of demonstrating that neurosteroids (including sex steroids) are synthesized locally by P450s in the brain, and that these steroids act acutely / non-genomically (or chronically / genomically) to modulate neuronal plasticity, as 4th generation neuromessengers. Because both the memory-related synaptic plasticity and the neonatal development of neuronal networks are significantly affected by the presence of neuroactive steroids, it is probable that estrogen-like EDs (e.g., bisphenol A (BPA), diethylstylbesterol (DES), etc.) have disruptive actions on these neuronal functions and properties. One of our primary concerns is the elucidation of these ED actions.
Our present work involves the search for estrogen receptors in the hippocampal neuronal synapses (i.e., synaptic estrogen receptors, that play a pivotal role in synaptic plasticity, learning and memory, with an eye towards establishing the biochemical basis for the observed acute ED actions on the synaptic plasticity. Because other leading laboratories in the field have yet to report the discovery of even classical nuclear estrogen receptors in principal hippocampal neurons, (B) we have also undertaken a vigorous effort in this regard, and have made some progress towards elucidation of the location of the synaptic estrogen receptors and estrogen receptor-dependent signal pathways which either acutely modulate the activity of an NMDA type glutamate receptor (a key factor in learning and memory), or chronically (within several days) increase the number of neuronal synapses (a storage area for short-term memory). This machinery has provided a promising mechanism by which estrogens may play an important role in enhancing the efficiency of synaptic plasticity in the hippocampus.
It is therefore quite reasonable to postulate that orally administered estrogen-like EDs might also disrupt synaptic transmission, when reaching neurons via the blood circulation and by crossing the blood-brain barrier. We have developed new techniques of capturing and analyzing the actions of EDs on synaptic estrogen receptor-dependent pathways at the molecular level. We study the action of EDs not only on adult brains (in which neuronal wiring development is completed), but also on fetal / neonatal brains (in which neuronal wiring is still under development).
For more information, see Environmental Sciences, 11, 1 (2004) 1-14 in Publications Section of this web site.
Team Leader of MEXT Project from 2003-
National Project of Special Coordinate Funds for Promoting Science and Technology
of Ministry of Education, XX, Science and Technology,
"Novel Multielectrode Analysis of Endocrine Disrupting of Learning and Memory"
For more information, see J.Nuerochem., 100 (2007) 950-967 in
Publications Section of this web site.
