• The Zoological Society Korea : Newsletter
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• v.18 no.1
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• pp.41-48
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• 2001

1980년대 초반에 'Neurosteroid'라는 개념이 소개 되면서, 지난 20년간 이 분야에 많은 연구결과들이 쌓이게 되었다. 그리고, neurosteroid는 과거에 알고 있었던 스테로이드들과는 다른 방법으로 생물체에 생리적 작용을 하는 것으로 알려졌으며, 특히 신경계 내에서는 신경전달물질과 같은 작용을 한다는 것이 알려지면서 신경계 내에서의 자체적인 스테로이드 호르몬 합성에 관한 연구들이 본격화되기 시작했다. 지난 10년 사이에 많은 review 논문들이 발표되고 있지만, neurosteroid와 신경계의 특성상스테로이드 호르몬의 신경계에 미치는 기능에 대한 연구가 쉽지 않으며, 정밀하게 조절되는 신경계의 스테로이드 함량변화를 조절하는 합성 효소에 대한 연구는 아직도 초보적인 단계에 머물러 있다. 이에 본 논단에서는 neurosteroid에 대한 소개와 함께 최근 우리실험실의 연구결과를 소개하고자 한다.

• Applied Biological Chemistry
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• v.40 no.2
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• pp.112-116
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• 1997

The enzymatic properties as well as its distribution in the cerebral region and subcellular organells were investigated for the neurosteroid acyltransferase from the bovine brain, which synthesize the fatty acid esters of the neurosteroids. The cerebellum region was the highest in NSAT activity while the cerebrum was the lowest with 50% of the cerebellar activity. The NSAT was found to be mainly localized in the microsomal fraction. The optimal temperature and pH were $40^{\circ}C$ and 4.9, respectively. When $^3H-DHEA$ was utilized as substrate, the $K_m$ and $V_{max}$ was $32.6\;{\mu}M$ and 4.86 nmole/mg protein/h, respectively. Under the same condition pregnenolone$({\Delta}^5P)$ was a competitive inhibitor with $K_i=22.8\;{\mu}M$ and testosterone was a uncompetitive inhibitor with $K_i=22.8\;{\mu}M$. This may suggest that the NSAT has a different conformation in the acylation of the ${\beta}-hydroxyl$ group at C-3 and C-17.

• Archives of Pharmacal Research
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• v.29 no.7
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• pp.566-569
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• 2006

This study examined whether or not acute stress is linked to increases in the neurosteroid levels, which is a well-known neurotransmitters associated with stress stimuli. The ginsenoside, Rb1, was tested in order to better understand its potential effects on altering the neurosteroid levels and ultimately attenuating stress. The optimal stressed condition was checked by measuring the 5a-dihydroprogesterone (DHP) and allopregnanolone (THP) levels in the brain after immobilization stress at various times. Based on this result, an acute stress model was set up to give 30 min of immobilization stress. The DHP and THP brain levels of the stressed mice were then investigated after administering Rb1 orally (10 mg/kg). These results were compared with the neurosteroid level in the stressed mice not given Rb1. Saline was administered orally to the nonstressed mice to check the placebo effect. Acute immobilization stress induced an increase in the THP and DHP concentration in the frontal cortex and cerebellum. When Rb1 was administered orally prior to immobilization stress, the THP level in the frontal cortex and cerebellum was significantly lower than that in the stressed animals not given Rb1. On the other hand, the DHP level was lower in the cerebellum only. This suggests that the metabolism of the brain neurosteroids is linked to psychological stress, and Rb1 attenuates the stressinduced increase in neurosteroids.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.6
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• pp.485-491
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• 2013

The present study was designed to investigate the putative effect of neurosteroid modulation on global ischaemia-reperfusion-induced cerebral injury in mice. Bilateral carotid artery occlusion followed by reperfusion, produced a significant rise in cerebral infarct size along with impairment of grip strength and motor coordination in Swiss albino mice. Administration of carbamazepine (16 mg/kg, i.p.) before global cerebral ischaemia significantly attenuated cerebral infarct size and improved the motor performance. However, administration of indomethacin (100 mg/kg, i.p.) attenuated the neuroprotective effect of carbamazepine. Mexiletine (50 mg/kg, i.p.) did not produce significant neuroprotective effect. It may be concluded that the neuroprotective effect of carbamazepine may be due to increase in synthesis of neurosteroids perhaps by activating enzyme ($3{\alpha}$ HSD) as indomethacin attenuated the neuroprotective effect of carbamazepine. The sodium channel blocking effect of carbamazepine may not be involved in neuroprotection as mexiletine, a sodium channel blocker, did not produce significant neuroprotective effect.

• Korean Journal of Veterinary Research
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• v.57 no.1
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• pp.47-50
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• 2017

Concentrations of cortisol, dehydroepiandrosterone and dehydroepiandrosterone-sulfate were measured by performing radioimmunoassay of the cerebrospinal fluid of 68 dogs diagnosed with idiopathic epilepsy or inflammatory, degenerative, or non-neurological disease. No steroid concentration differences were found among diagnoses. Dehydroepiandrosterone and dehydroepiandrosterone-sulfate concentrations were higher in males than in females and dehydroepiandrosterone-sulfate decreased with increasing age. No sex or age effects were observed on cortisol or hormone ratios. Although limited to a relatively small sample, our results show sex- and age-dependent variations in these neurosteroid concentrations in cerebrospinal fluid. The role of such variations in the pathophysiology of the dog brain warrants further investigation.

• The Korean Journal of Pain
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• v.28 no.1
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• pp.4-10
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• 2015

Etifoxine (etafenoxine, $Stresam^{(R)}$) is a non-benzodiazepine anxiolytic with an anticonvulsant effect. It was developed in the 1960s for anxiety disorders and is currently being studied for its ability to promote peripheral nerve healing and to treat chemotherapy-induced pain. In addition to being mediated by $GABA_A{\alpha}2$ receptors like benzodiazepines, etifoxine appears to produce anxiolytic effects directly by binding to ${\beta}2$ or ${\beta}3$ subunits of the $GABA_A$ receptor complex. It also modulates $GABA_A$ receptors indirectly via stimulation of neurosteroid production after etifoxine binds to the 18 kDa translocator protein (TSPO) of the outer mitochondrial membrane in the central and peripheral nervous systems, previously known as the peripheral benzodiazepine receptor (PBR). Therefore, the effects of etifoxine are not completely reversed by the benzodiazepine antagonist flumazenil. Etifoxine is used for various emotional and bodily reactions followed by anxiety. It is contraindicated in situations such as shock, severely impaired liver or kidney function, and severe respiratory failure. The average dosage is 150 mg per day for no more than 12 weeks. The most common adverse effect is drowsiness at the initial stage. It does not usually cause any withdrawal syndromes. In conclusion, etifoxine shows less adverse effects of anterograde amnesia, sedation, impaired psychomotor performance, and withdrawal syndromes than those of benzodiazepines. It potentiates $GABA_A$ receptor-function by a direct allosteric effect and by an indirect mechanism involving the activation of TSPO. It seems promising that non-benzodiazepine anxiolytics including etifoxine will replenish shortcomings of benzodiazepines and selective serotonin reuptake inhibitors according to animated studies related to TSPO.