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Department of Pharmacology

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Overview

Our laboratory research interests focus on:

1) We are investigating the molecular mechanism through which ischemia generates the lower urinary tract symptoms (overactive bladder and benign prostatic hyperplasia), sexual dysfunction and testicular dysfunction. Also, psychological stress or strain is known to play an important role in the induction of urinary frequency and lower urinary tract symptoms including the overactive bladder and painful bladder syndrome/interstitial cystitis. However, the pathophysiological mechanism underlying the stress causing urinary frequency is not well understood. In our laboratory, the molecular mechanism on how psychological stress related neurotransmitters affect the urination is under investigation.

2) Microglia are the resident immune cells in the central nervous system. Under normal physiological conditions, microglia are characterized by ramified morphology and occupy their own territory, which make it convenient to monitor the microenvironment in their territory. On the other hand, microglia become activated in response to neuronal injury following brain ischemia and trauma. The activated microglia can exhibit either protective or detrimental function depending on their activation state (classical activation and alternative activation). Recently, microenvironment has been suggested to play roles in the regulation of microglial activation state. But mechanism underlying microenvironment-regulated microglial activation is not fully understood. In our laboratory, we have been examining the roles of extracellular zinc in the microglial activation and function.

3) Stress responses, the body’s responses to stress stimuli, are essential for adaptation to stress. On the other hand, prolonged or excessive activation of the responses could contribute to the development of stress-related disorders including hypertension and depression. Stress-related information is conveyed to the brain, which recruits neuronal and neuroendocrine systems for induction of stress responses. Therefore, focusing on the brain, we have been examining the central regulation mechanisms of stress responses in order to create novel therapeutical strategies for the stress-related diseases.

Research areas

1. Molecular mechanism and new treatment strategy for lower urinary tract symptoms and sexual dysfunction

 We have previously demonstrated that the decreased pelvic blood flow could cause detrusor overactivity, benign prostatic hyperplasia and erectile dysfunction using animal models. At present, we are investigating intensively the precise molecular mechanism by employing a pharmacological approach. Moreover, we are investigating the effect of intra-cerebroventricularlly administered stress-related neurotransmitters on the rat urodynamic parameters.

2. Molecular mechanism and new preventive strategy for sequelea of inflammatory brain disorders

 In mammalian brain, zinc is present in a subset of glutamatergic axon terminals throughout the forebrain, especially in the hippocampus. Under severe conditions such as cerebral ischemia, excessive amount of zinc stored in presynaptic glutamatergic neurons is released into the extracellular space. We have previously demonstrated extracellular zinc is a novel trigger for microglial activation, and revealed zinc-induced microglial activation signaling pathway. At present, we are investigating the roles of zinc-activated microglia in sequelae of inflammatory brain disorders.

3. Novel therapeutical strategies for the stress-related diseases developed by prolonged or excessive activation of stress responses

 Focusing on the sympatho-adrenomedullary system, an essential mechanism for adaptation to stress, we have been examining central regulation mechanisms of the system activated by stress-related neurotransmitters. In general, the sympatho-adrenomedullary system can regulate blood pressure and micturition. That’s why we have been also examining central mechanisms of stress-induced hypertension and urinary bladder dysfunction focusing on the regulation mechanisms of the sympatho-adrenomedullary system.

Staff

Professor: Motoaki Saito
Associate Professor: Takahiro Shimizu
Assistant Lecturer: Yoichirou Higashi
Assistant Lecturer: Shogo Shimizu
Kochi Medical School Department of Neurobiology and Anatomy

Kochi Medical School
Department of Pharmacology

http://www.kochi-ms.ac.jp/~ff_phrmc/

Tel: +81-88-880-2327