Potentiation of NMDA Receptors byWithania somniferaon Hippocampal CA1 Pyramidal Neurons

Abstract

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.

Stachys sieboldii Extract Supplementation Attenuates Memory Deficits by Modulating BDNF-CREB and Its Downstream Molecules, in Animal Models of Memory Impairment

“…In addition, the inward currents induced by SS were partially blocked by picrotoxin, a broad GABA A receptor antagonist, suggesting that SS exhibits GABA-mimetic activity via synaptic and extrasynaptic GABA A receptors ( Figure 8 G,H). This provides evidence that SS acts directly on the GABA binding site of CA1 pyramidal neurons in the hippocampus [ 17 ]. These results are in agreement with a previous study [ 38 ], which reported that Withania somnifera acts at a GABA receptor by inhibiting GABA A receptor agonists.…”

“…Brain slices were prepared as described by [ 17 ] earlier study with slight modifications in position of brain used. Immature ICR male mice (5–20 Postnatal days) were sacrificed by cervical dislocation between 10:00 and 12:00 h and their brains rapidly removed and placed in the ice-cold low calcium (0.5 mM), high magnesium (6 mM) bicarbonate-buffered artificial cerebrospinal fluid (ACSF) (pH 7.4 when bubbled with 95% O 2 and 5% CO 2 )).…”

“…GABA A R activation also controls the formation and plasticity of GABAergic synapses, results in the normalizing the cognitive impairment [ 15 ]. In addition, pharmacological findings show that traditional drugs acting at GABAergic receptors have memory active properties [ 16 , 17 ].…”

Effect of withinia somnifera and shilajit on alcohol addiction in mice

“…A plasma and CSF level of GABA is higher after initial withdrawal than after longer periods of abstinence. [ 47 ] Diazepam, an established GABA A agonist and anti-addictive compound, also showed increase in corticohippocampal GABA levels. Similar to previous reports, we also found an increase in serotonin levels in the corticohippocampal lysates of ethanol-exposed animals[ 44 48 ] suggesting either excess release or reduced uptake of serotonin.…”