Potentiation of NMDA receptors by Withania somnifera on hippocampal CA1 pyramidal neurons.

Bhattarai, Janardhan Prasad,Park, Soo Joung,Han, Seong Kyu Institute for Advanced Research in Asian Science a 2013 The American journal of Chinese medicine Vol.41 No.3

<P>In Ayurveda,Withania somnifera (WS) is used as a medicine to maintain mental and physical health as well as to enhance memory. In this study, the methanolic extract of WS(mWS) was tested for its electrical influence on hippocampal CA1 pyramidal neurons using a patch clamp technique. In current clamp mode under a high chloride pipette solution, mWS (400 ng/μl) induced remarkable membrane depolarization (9.75 2.54 mV, n = 6) of CA1 neurons. The mWS-induced depolarization was dose-dependent, reproducible, and persistent in the presence of 0.5 μM tetrodotoxin (TTX, 10.17 0.04 mV, n = 6). In voltage clamp mode (holding potential = -60 mV), mWS induced a dose-dependent non-desensitizing inward current that persisted in the presence of TTX (0.5 μM), suggesting that the response induced by mWS was purely a postsynaptic event. Interestingly, these inward currents were partially blocked by strychnine, a glycine receptor blocker. Further, mWS potentiated the NMDA response in hippocampal CA1 neurons at low concentrations. Overall, these results suggest that there are compounds in WS with possible glycine mimetic activities, which may be potential targets for inducing memory consolidation in hippocampal CA1 neurons.</P>

Activation of Strychnine-Sensitive Glycine Receptors by Shilajit on Preoptic Hypothalamic Neurons of Juvenile Mice

Medknow Publications 2016 The Chinese journal of physiology Vol.59 No.1

<P>Shilajit, a mineral pitch, has been used in Ayurveda and Siddha system of medicine to treat many human ailments, and is reported to contain at least 85 minerals in ionic form. This study examined the possible mechanism of Shilajit action on preoptic hypothalamic neurons using juvenile mice. The hypothalamic neurons are the key regulator of many hormonal systems. In voltage clamp mode at a holding potential of -60 mV, and under a high chloride pipette solution, Shilajit induced dose-dependent inward current. Shilajit-induced inward currents were reproducible and persisted in the presence of 0.5 mu M tetrodotoxin (TTX) suggesting a postsynaptic action of Shilajit on hypothalamic neurons. The currents induced by Shilajit were almost completely blocked by 2 mu M strychnine (Stry), a glycine receptor antagonist. In addition, Shilajit-induced inward currents were partially blocked by bicuculline. Under a gramicidin-perforated patch clamp mode, Shilajit induced membrane depolarization on juvenile neurons. These results show that Shilajit affects hypothalamic neuronal activities by activating the Stry-sensitive glycine receptor with alpha(2)/alpha(2)beta subunit. Taken together, these results suggest that Shilajit contains some ingredients with possible glycine mimetic activities and might influence hypothalamic neurophysiology through activation of Stry-sensitive glycine receptor-mediated responses on hypothalamic neurons postsynaptically.</P>

Nitric oxide suppresses L-type calcium currents in basilar artery smooth muscle cells in rabbits

Sharma, Naveen,Bhattarai, Janardhan Prasad,Hwang, Pyoung Han,Han, Seong Kyu Informa UK (TaylorFrancis) 2013 Neurological research Vol.35 No.4

<P>Nitric oxide (NO) is well known to be a vasodilator, and NO donor compounds are currently used for treating vasospasm following subarachnoid hemorrhage. However, the action mechanism of cerebral vascular relaxation is not yet clear. L-type calcium channels have been determined to play an essential role in smooth muscle contraction. To investigate the role of L-type calcium channels in NO-induced relaxation of basilar smooth muscle cells, we examined the effect of the NO donor, sodium nitroprusside (SNP) on calcium (Ca2+) currents using smooth muscle cells isolated from a rabbit basilar artery.</P>

GABA<SUB>A</SUB> Receptor- and Non-NMDA Glutamate Receptor-Mediated Actions of Korean Red Ginseng Extract on the Gonadotropin Releasing Hormone Neurons

Dong Hyu Cho,Janardhan Prasad Bhattarai,Seong Kyu Han 고려인삼학회 2012 Journal of Ginseng Research Vol.36 No.1

Korean red ginseng (KRG) has been used worldwide as a traditional medicine for the treatment of various reproductive diseases. Gonadotropin releasing hormone (GnRH) neurons are the fundamental regulators of pulsatile release of gonadotropin required for fertility. In this study, an extract of KRG (KRGE) was applied to GnRH neurons to identify the receptors activated by KRGE. The brain slice patch clamp technique in whole cell and perforated patch was used to clarify the effect of KRGE on the membrane currents and membrane potentials of GnRH neurons. Application of KRGE (3 ㎍/μL) under whole cell patch induced remarkable inward currents (56.17±7.45 pA, n=25) and depolarization (12.91±3.80 ㎷, n=4) in GnRH neurons under high Cl? pipette solution condition. These inward currents were not only reproducible, but also concentration dependent. In addition, inward currents and depolarization induced by KRGE persisted in the presence of the voltage gated Na? channel blocker tetrodotoxin (TTX), suggesting that the responses by KRGE were postsynaptic events. Application of KRGE under the gramicidin perforated patch induced depolarization in the presence of TTX suggesting its physiological signifi cance on GnRH response. Further, the KRGEinduced inward currents were partially blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; non-NMDA glutamate receptor antagonist, 10 μM) or picrotoxin (PIC; GABAA receptor antagonist, 50 μM), and almost blocked by PIC and CNQX mixture. Taken together, these results suggest that KRGE contains ingredients with possible GABA and non-NMDA glutamate receptor mimetic activity, and may play an important role in the endocrine function of reproductive physiology, via activation of GABAA and non-NMDA glutamate receptors in GnRH neurons.

GABA_A Receptor- and Non-NMDA Glutamate Receptor-Mediated Actions of Korean Red Ginseng Extract on the Gonadotropin Releasing Hormone Neurons

Cho, Dong-Hyu,Bhattarai, Janardhan Prasad,Han, Seong-Kyu The Korean Society of Ginseng 2012 Journal of Ginseng Research Vol.36 No.1

Korean red ginseng (KRG) has been used worldwide as a traditional medicine for the treatment of various reproductive diseases. Gonadotropin releasing hormone (GnRH) neurons are the fundamental regulators of pulsatile release of gonadotropin required for fertility. In this study, an extract of KRG (KRGE) was applied to GnRH neurons to identify the receptors activated by KRGE. The brain slice patch clamp technique in whole cell and perforated patch was used to clarify the effect of KRGE on the membrane currents and membrane potentials of GnRH neurons. Application of KRGE (3 ${\mu}g$/${\mu}L$) under whole cell patch induced remarkable inward currents (56.17${\pm}$7.45 pA, n=25) and depolarization (12.91${\pm}$3.80 mV, n=4) in GnRH neurons under high $Cl^-$ pipette solution condition. These inward currents were not only reproducible, but also concentration dependent. In addition, inward currents and depolarization induced by KRGE persisted in the presence of the voltage gated $Na^+$ channel blocker tetrodotoxin (TTX), suggesting that the responses by KRGE were postsynaptic events. Application of KRGE under the gramicidin perforated patch induced depolarization in the presence of TTX suggesting its physiological significance on GnRH response. Further, the KRGE-induced inward currents were partially blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; non-NMDA glutamate receptor antagonist, 10 ${\mu}M$) or picrotoxin (PIC; $GABA_A$ receptor antagonist, 50 ${\mu}M$), and almost blocked by PIC and CNQX mixture. Taken together, these results suggest that KRGE contains ingredients with possible GABA and non-NMDA glutamate receptor mimetic activity, and may play an important role in the endocrine function of reproductive physiology, via activation of $GABA_A$ and non-NMDA glutamate receptors in GnRH neurons.

Memory ameliorative effect of Stachys siedlbodii MIQ extract on mice hippocampal CA1 pyramidal neuron

Ravichandran Vijaya Abinaya,Janardhan Prasad Bhattarai,Seong Kyu Han,Mina Kim,Youn-Soo Cha 한국식품영양과학회 2016 한국식품영양과학회 학술대회발표집 Vol.2016 No.10

Magnesium sulfate suppresses L-type calcium currents on the basilar artery smooth muscle cells in rabbits

Sharma, Naveen,Cho, Dong Hyu,Kim, Sun Young,Bhattarai, Janardhan Prasad,Hwang, Pyoung Han,Han, Seong Kyu Informa UK (TaylorFrancis) 2012 Neurological research Vol.34 No.3

<P>Although magnesium is a well-known treatment for vasospasm following subarachnoid hemorrhage, its mechanism of action for cerebral vascular relaxation is not clear. In addition, it is known that L-type calcium (Ca(2+)) channels play a pivotal role in smooth muscle contraction. To investigate the role of L-type Ca(2+) channels in the magnesium-induced relaxation of basilar smooth muscle cells, we examined the effect of magnesium sulfate on L-type Ca(2+) currents using freshly isolated smooth muscle cells from rabbit basilar arteries.</P>