scholarly journals Antidepressant-like action of diacamphe against the background stress-induced behavioral depression

2018 ◽  
Vol 26 (3) ◽  
pp. 351-359
Author(s):  
Tamara O. Zayka ◽  
Dmitriy V. Evdokimov ◽  
Igor I. Abramets
Keyword(s):  
Pyramidal Neurons ◽  
Carbonic Acid ◽  
Hippocampal Slices ◽  
Neuroprotective Activity ◽  
Behavioral Experiments ◽  
Behavioral Depression ◽  
Swimming Stress ◽  
Antidepressant Imipramine ◽  
Swimming Test

Background. It was find out the cerebroprotective properties of diacamphe – (±)-cis-3-(2’-benzimidazolyl)-1,2,2-trimethylcyclopentan-carbonic acid hydrochloride in vivo experiments in the some models of brain injury. Aim. To investigate the neuroprotective and antidepressant-like activities of diacamphe. Materials and Methods. It was investigated an impact of diacamphe on inhibition of the pyramidal neurons field synaptic potentials evoked by N-methyl-D-aspartate, procedure anoxia/neuroaglicemia, and H2O2 in the electrophysiological experiments on hippocampal slices for evaluating of diacamphe neuroprotective activity. It was explored in behavioral experiments the impacts of diacamphe and antidepressant imipramine on basic manifestations of behavioral depression evoked by five-days swimming stress – helplessness and anhedonia. Results. It was ascertained in experiments on the hippocampal slices that diacamphe especially at conditions of systemic administration diminished of injury of the pyramidal neurons synapses induced by procedure anoxya/aglicemia, oxidative stress, but not N-methyl-D-aspartate action. The chronic administration of diacamphe in dose 10 mg/kg reduced the manifestations of induced by swimming stress behavioral depression, decrease duration of immobility in forced swimming test (helplessness) and increase preference of intake of sweet solution comparably with water (dilution of anhedonia). Antidepressant-like action of diacamphe differences from action of traditional antidepressant imipramine so far as diacamphe did not diminishes immobilization duration in swimming test after single administration and by more slow developing of action. Conclusions. Diacamphe possesses neuroprotective action and therefore manifests antidepressant-like action against the background behavioral depression evoked by swimming stress.

scholarly journals Antidepressant-like action of diacamphe against the background stress-induced behavioral depression

2018 ◽  
Vol 26 (3) ◽  
pp. 351-359
Author(s):  
Tamara O. Zayka ◽  
Dmitriy V. Evdokimov ◽  
Igor I. Abramets
Keyword(s):  
Pyramidal Neurons ◽  
Carbonic Acid ◽  
Hippocampal Slices ◽  
Neuroprotective Activity ◽  
Behavioral Experiments ◽  
Behavioral Depression ◽  
Swimming Stress ◽  
Antidepressant Imipramine ◽  
Swimming Test

Background. It was find out the cerebroprotective properties of diacamphe – (±)-cis-3-(2’-benzimidazolyl)-1,2,2-trimethylcyclopentan-carbonic acid hydrochloride in vivo experiments in the some models of brain injury. Aim. To investigate the neuroprotective and antidepressant-like activities of diacamphe. Materials and Methods. It was investigated an impact of diacamphe on inhibition of the pyramidal neurons field synaptic potentials evoked by N-methyl-D-aspartate, procedure anoxia/neuroaglicemia, and H2O2 in the electrophysiological experiments on hippocampal slices for evaluating of diacamphe neuroprotective activity. It was explored in behavioral experiments the impacts of diacamphe and antidepressant imipramine on basic manifestations of behavioral depression evoked by five-days swimming stress – helplessness and anhedonia. Results. It was ascertained in experiments on the hippocampal slices that diacamphe especially at conditions of systemic administration diminished of injury of the pyramidal neurons synapses induced by procedure anoxya/aglicemia, oxidative stress, but not N-methyl-D-aspartate action. The chronic administration of diacamphe in dose 10 mg/kg reduced the manifestations of induced by swimming stress behavioral depression, decrease duration of immobility in forced swimming test (helplessness) and increase preference of intake of sweet solution comparably with water (dilution of anhedonia). Antidepressant-like action of diacamphe differences from action of traditional antidepressant imipramine so far as diacamphe did not diminishes immobilization duration in swimming test after single administration and by more slow developing of action. Conclusions. Diacamphe possesses neuroprotective action and therefore manifests antidepressant-like action against the background behavioral depression evoked by swimming stress.

scholarly journals Optogenetic activation of SST-positive interneurons restores hippocampal theta oscillation impairment induced by soluble amyloid beta oligomersin vivo

2018 ◽  
Author(s):  
Hyowon Chung ◽  
Kyerl Park ◽  
Hyun Jae Jang ◽  
Michael M Kohl ◽  
Jeehyun Kwag
Keyword(s):  
Learning And Memory ◽  
Peak Power ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Field Potential ◽  
Theta Oscillations ◽  
Ca1 Pyramidal Neurons ◽  
Theta Frequency ◽  
Hippocampal Theta

AbstractAbnormal accumulation of amyloid β oligomers (AβO) is a hallmark of Alzheimer’s disease (AD), which leads to learning and memory deficits. Hippocampal theta oscillations that are critical in spatial navigation, learning and memory are impaired in AD. Since GABAergic interneurons, such as somatostatin-positive (SST+) and parvalbumin-positive (PV+) interneurons, are believed to play key roles in the hippocampal oscillogenesis, we asked whether AβO selectively impairs these SST+ and PV+ interneurons. To selectively manipulate SST+ or PV+ interneuron activity in mice with AβO pathologyin vivo, we co-injected AβO and adeno-associated virus (AAV) for expressing floxed channelrhodopsin-2 (ChR2) into the hippocampus of SST-Cre or PV-Cre mice. Local field potential (LFP) recordingsin vivoin these AβO–injected mice showed a reduction in the peak power of theta oscillations and desynchronization of spikes from CA1 pyramidal neurons relative to theta oscillations compared to those in control mice. Optogenetic-activation of SST+ but not PV+ interneurons in AβO–injected mice fully restored the peak power of theta oscillations and resynchronized the theta spike phases to a level observed in control mice.In vitrowhole-cell voltage-clamp recordings in CA1 pyramidal neurons in hippocampal slices treated with AβO revealed that short-term plasticity of SST+ interneuron inhibitory inputs to CA1 pyramidal neurons at theta frequency were selectively disrupted while that of PV+ interneuron inputs were unaffected. Together, our results suggest that dysfunction in inputs from SST+ interneurons to CA1 pyramidal neurons may underlie the impairment of theta oscillations observed in AβO-injected micein vivo.Our findings identify SST+ interneurons as a target for restoring theta-frequency oscillations in early AD.

scholarly journals Studies of the effect of cerebroprotective substances on the course of stress-induced behavioral depression

2018 ◽  
Vol 4 (3) ◽  
pp. 43-48
Author(s):  
Tamara O. Zaika ◽  
Dmitriy V. Evdokimov ◽  
Igor I. Abramets
Keyword(s):  
Hippocampal Neurons ◽  
Sucrose Solution ◽  
Forced Swim Test ◽  
Hippocampal Slices ◽  
Chronic Administration ◽  
Behavioral Experiments ◽  
Behavioral Depression ◽  
Swim Test ◽  
Cerebroprotective Activity

Introduction. Atrophic disturbances of neurons of the limbic structures of the brain, which lead to insufficient regulation of emotions and mood, cause depression. Substances with cerebroprotective activity have the ability to inhibit further development and even reverse atrophic damage to neurons. Materials and methods. Using electrophysiological techniques, the cerebroprotective activity of piracetam, diacamf – (±)-cis-3-(2-benzimidazolyl)-1,2,2-trimethylcyclopentanone-carboxylic acid hydrochloride and the compound R-86, or 3,2’-spiro-pyrrolo-2-oxindole, was investigated in rat hippocampal slices. In behavioral experiments, there was studied the influence of the above substances, which had been administered for 20 days, on the most important manifestations of behavioral depression in rats caused by a five-day swim stress, such as the time of immobilization in the forced swim test and the indicator of preference for consuming sucrose solution. In addition, the influence of piracetam and diacamf was studied on the effects of the classic antidepressant imipramine. Results and discussion. It was found that piracetam, diacamf and the compound R-86 in in vitro studies reduced the damage to the pyramidal hippocampal neurons caused by anoxia and aglycemia, the excitotoxic activity of N-methyl-D-aspartate and oxidative stress when hydrogen peroxide was applied to the slices. Cerebroprotective activity of the test substances, when they are systemically administered for 20 days, is linked with their antidepressant-like effect, which was manifested in a decrease in the immobilization time in the swim test and an increase in the sucrose solution consumption indicator. Co-administration of piracetam in rats potentiated antidepressant activity of imipramine, and diacamf showed additive synergism with the antidepressant. Conclusion. Substances with cerebroprotective activity in their chronic administration may show an antidepressant-like effect. Those that potentiate the action of classical anidepressants can be used in conjunction with antidepressants during episodes of exacerbation of the disease. Less active cerebroprotective drugs can be recommended during remission for its prolongation.

scholarly journals Streptozotocin Inhibits Electrophysiological Determinants of Excitatory and Inhibitory Synaptic Transmission in CA1 Pyramidal Neurons of Rat Hippocampal Slices: Reduction of These Effects by Edaravone

2016 ◽  
Vol 40 (6) ◽  
pp. 1274-1288 ◽  
Author(s):  
Ting Ju ◽  
Yuru Li ◽  
Xiaoran Wang ◽  
Lifeng Xiao ◽  
Li Jiang ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Paired Pulse ◽  
Ca1 Pyramidal Neurons ◽  
Postsynaptic Currents ◽  
Pulse Ratio ◽  
Synaptic Mechanisms

Background: Streptozotocin (STZ) has served as an agent to generate an Alzheimer's disease (AD) model in rats, while edaravone (EDA), a novel free radical scavenger, has recently emerged as an effective treatment for use in vivo and vitro AD models. However, to date, these beneficial effects of EDA have only been clearly demonstrated within STZ-induced animal models of AD and in cell models of AD. A better understanding of the mechanisms of EDA may provide the opportunity for their clinical application in the treatment of AD. Therefore, the purpose of this study was to investigate the underlying mechanisms of STZ and EDA as assessed upon electrophysiological alterations in CA1 pyramidal neurons of rat hippocampal slices. Methods: Through measures of evoked excitatory postsynaptic currents (eEPSCs), AMPAR-mediated eEPSCs (eEPSCsAMPA), evoked inhibitory postsynaptic currents (eIPSCs), evoked excitatory postsynaptic current paired pulse ratio (eEPSC PPR) and evoked inhibitory postsynaptic current paired pulse ratio (eIPSC PPR), it was possible to investigate mechanisms as related to the neurotoxicity of STZ and reductions in these effects by EDA. Results: Our results showed that STZ (1000 µM) significantly inhibited peak amplitudes of eEPSCs, eEPSCsAMPA and eIPSCs, while EDA (1000 µM) attenuated these STZ-induced changes at holding potentials ranging from -60mV to +40 mV for EPSCs and -60mV to +20 mV for IPSCs. Our work also indicated that mean eEPSC PPR were substantially altered by STZ, effects which were partially restored by EDA. In contrast, no significant effects upon eIPSC PPR were obtained in response to STZ and EDA. Conclusion: Our data suggest that STZ inhibits glutamatergic transmission involving pre-synaptic mechanisms and AMPAR, and that STZ inhibits GABAergic transmission by post-synaptic mechanisms within CA1 pyramidal neurons. These effects are attenuated by EDA.

Ethanol Alters the Frequency, Amplitude, and Decay Kinetics of Sr2+-Supported, Asynchronous NMDAR mEPSCs in Rat Hippocampal Slices

2004 ◽  
Vol 91 (6) ◽  
pp. 2568-2577 ◽  
Author(s):  
Adam W. Hendricson ◽  
John R. Sibbald ◽  
Richard A. Morrisett
Keyword(s):  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Mean Amplitude ◽  
Long Term Potentiation ◽  
Exponential Fitting ◽  
Decay Kinetics ◽  
Current Decay ◽  
Event Frequency

To discriminate between pre- and postsynaptic effects of ethanol on N-methyl-d-aspartate receptor (NMDAR) signaling in hippocampus, we adapted the technique of Sr2+ substitution to the hippocampal blind slice patch-clamp preparation. Hippocampal slices were isolated from 12- to 20-day-old rats that were killed in accordance with University of Texas Institutional Animal Care and Use Committee guidelines. NMDAR miniature excitatory postsynaptic currents (mEPSCs) were evoked from CA1 pyramidal neurons in the presence of Sr2+ (4 mM), causing the synchronous EPSC observed in the presence of Ca2+ to be supplanted by asynchronous mEPSCs. Amplitudes typically ranged from 5 to 40 pA and responded to the NMDAR antagonist (DL)-APV (50 μM), with a statistically significant reduction in mean amplitude. Ethanol (25, 50, and 75 mM) exerted dose-dependent effects on mEPSC amplitude and frequency. Peak amplitude inhibition was observed at 75 mM ethanol. Notably, ethanol significantly decreased event frequency at 50 and 75 mM ethanol. Ethanol (75 mM) also significantly increased the paired-pulse ratio of NMDAR EPSCs. Cumulative comparisons of decay time constants derived from single-exponential fitting of mEPSCs revealed significantly accelerated current decay kinetics in the presence of 75 mM ethanol. Taken together, these reductions in miniature event frequency and amplitude, concurrent with an increased rate of decay, suggest that the acute effects of ethanol on NMDAR signaling at hippocampal synapses are multifocal in nature. This finding of pre- and postsynaptic effects of ethanol on NMDAR signal strength in a brain region central to cognition is wholly consistent with previous reports of ethanol inhibition of NMDAR–long-term potentiation in vitro and with the profound cognitive deficits associated with binge-level intoxication in vivo.

scholarly journals Vasopressin acts as a synapse organizer in limbic regions by boosting PSD95 and GluA1 expression

2020 ◽  
Author(s):  
Limei Zhang ◽  
Teresa Padilla-Flores ◽  
Vito S. Hernández ◽  
Elba Campos-Lira ◽  
Mario A. Zetter ◽  
...  
Keyword(s):  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Ex Vivo ◽  
Hippocampal Slices ◽  
Brain Slices ◽  
Synaptic Proteins ◽  
Scaffolding Protein ◽  
Synaptic Organization ◽  
Limbic Regions

AbstractHypothalamic arginine vasopressin (AVP)-containing magnocellular neurosecretory neurons (AVPMNN) emit collaterals to synaptically innervate limbic regions influencing learning, motivational behavior and fear responses. The purpose of the present work is to characterize the dynamics of expression changes of two postsynaptic density (PSD) proteins, AMPAR subunit GluA1 and PSD scaffolding protein 95 (PSD95), which are known to be key determinants for synaptic strength, in response to in vivo and ex vivo manipulations of AVPMNN neuronal activation state, or exposure to exogenous AVP, metabolites and some signaling pathway inhibitors. Both long term water deprivation in vivo, which powerfully upregulates AVPMNN activity, and exogenous APV application ex vivo in brain slices, increased GluA1 and PSD95 expression and enhanced neuronal excitability in ventral hippocampal CA1 pyramidal neurons. Involvement of PI3k signaling in AVP-dependent plasticity is suggested by blockade of both AVP-induced protein up-regulation and enhanced neuronal excitability by the PI3k blocker wortmannin in hippocampal slices. We interpret these results as part of vasopressin’s central effects on synaptic organization in limbic regions modulating the strength of a specific set of synaptic proteins in hypothalamic-limbic circuits.Supported by grantsUNAM-DGAPA-PAPIIT-IN216918 & CONACYT-CB-238744.

scholarly journals Enhanced Neuronal Damage After Ischemic Insults in Mice Lacking Kir6.2-Containing ATP-Sensitive K+ Channels

2006 ◽  
Vol 95 (4) ◽  
pp. 2590-2601 ◽  
Author(s):  
Hong-Shuo Sun ◽  
Zhong-Ping Feng ◽  
Takashi Miki ◽  
Susumu Seino ◽  
Robert J. French
Keyword(s):  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Neuronal Damage ◽  
Focal Cerebral Ischemia ◽  
Hippocampal Slices ◽  
Immunocytochemical Staining ◽  
Sulfonylurea Receptor ◽  
Ca1 Pyramidal Neurons

Adenosine triphosphate (ATP)–sensitive potassium (KATP) channels, incorporating Kir6.x and sulfonylurea receptor subunits, are weak inward rectifiers that are thought to play a role in neuronal protection from ischemic insults. However, the involvement of Kir6.2-containing KATP channel in hippocampus and neocortex has not been tested directly. To delineate the physiological roles of Kir6.2 channels in the CNS, we used knockout (KO) mice that do not express Kir6.2. Immunocytochemical staining demonstrated that Kir6.2 protein was expressed robustly in hippocampal neurons of the wild-type (WT) mice and absent in the KO. To examine neuronal sensitivity to metabolic stress in vitro, and to ischemia in vivo, we 1) exposed hippocampal slices to transient oxygen and glucose deprivation (OGD) and 2) produced focal cerebral ischemia by middle cerebral artery occlusion (MCAO). Both slice and whole animal studies showed that neurons from the KO mice were severely damaged after anoxia or ischemia, whereas few injured neurons were observed in the WT, suggesting that Kir6.2 channels are necessary to protect neurons from ischemic insults. Membrane potential recordings from the WT CA1 pyramidal neurons showed a biphasic response to OGD; a brief hyperpolarization was followed by a small depolarization during OGD, with complete recovery within 30 min after returning to normoxic conditions. By contrast, CA1 pyramidal neurons from the KO mice were irreversibly depolarized by OGD exposure, without any preceding hyperpolarization. These data suggest that expression of Kir6.2 channels prevents prolonged depolarization of neurons resulting from acute hypoxic or ischemic insults, and thus protects these central neurons from the injury.

scholarly journals Rapid Fragmentation of the Endoplasmic Reticulum in Cortical Neurons of the Mouse Brain in situ Following Cardiac Arrest

2011 ◽  
Vol 31 (8) ◽  
pp. 1663-1667 ◽  
Author(s):  
Krzysztof Kucharz ◽  
Tadeusz Wieloch ◽  
Håkan Toresson
Keyword(s):  
Endoplasmic Reticulum ◽  
Cardiac Arrest ◽  
Mouse Brain ◽  
Cortical Neurons ◽  
Laser Scanning ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Primary Cultures ◽  
Laser Scanning Microscopy

Neuronal endoplasmic reticulum (ER), continuous from soma to dendritic spines, undergoes rapid fragmentation in response to N-methyl-D-aspartate (NMDA) receptor stimulation in hippocampal slices and neuronal primary cultures. Here, we show that ER fragments in the mouse brain following cardiac arrest (CA) induced brain ischemia. The ER structure was assessed in vivo in cortical pyramidal neurons in transgenic mice expressing ER-targeted GFP using two-photon laser scanning microscopy with fluorescence recovery after photobleaching (FRAP). Endoplasmic reticulum fragmentation occurred 1 to 2 minutes after CA and once induced, fragmentation was rapid (< 15 seconds). We propose that acute ER fragmentation may be a protective response against severe ischemic stress.

Background Activity Regulates Excitability of Rat Hippocampal CA1 Pyramidal Neurons by Adaptation of a K+ Conductance

2006 ◽  
Vol 95 (3) ◽  
pp. 2007-2012 ◽  
Author(s):  
Ingrid van Welie ◽  
Johannes A. van Hooft ◽  
Wytse J. Wadman
Keyword(s):  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Dynamic Range ◽  
Background Activity ◽  
Hippocampal Slices ◽  
Synaptic Activity ◽  
Input Output ◽  
Ca1 Pyramidal Neurons

In the in vivo brain background synaptic activity has a strong modulatory influence on neuronal excitability. Here we report that in rat hippocampal slices, blockade of endogenous in vitro background activity results in an increased excitability of CA1 pyramidal neurons within tens of minutes. The increase in excitability constitutes a leftward shift in the input–output relationship of pyramidal neurons, indicating a reduced threshold for the induction of action potentials. The increase in excitability results from an adaptive decrease in a sustained K+ conductance, as recorded from somatic cell–attached patches. After 20 min of blockade of background activity, the mean sustained K+ current amplitude in somatic patches was reduced to 46 ± 9% of that in time-matched control patches. Blockade of background activity did not affect fast Na+ conductance. Together, these results suggests that the reduction in K+ conductance serves as an adaptive mechanism to increase the excitability of CA1 pyramidal neurons in response to changes in background activity such that the dynamic range of the input–output relationship is effectively maintained.

scholarly journals Preconditioning In Vivo Ischemia Inhibits Anoxic Long-Term Potentiation and Functionally Protects CA1 Neurons in the Gerbil

1998 ◽  
Vol 18 (3) ◽  
pp. 288-296 ◽  
Author(s):  
Kensuke Kawai ◽  
Tadayoshi Nakagomi ◽  
Takaaki Kirino ◽  
Akira Tamura ◽  
Nobufumi Kawai
Keyword(s):  
Nmda Receptor ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Forebrain Ischemia ◽  
Term Potentiation ◽  
Induced Tolerance

Preconditioning with sublethal ischemia induces tolerance to subsequent lethal ischemia in neurons. We investigated electrophysiologic aspects of the ischemic tolerance phenomenon in the gerbil hippocampus. Gerbils were subjected to 2 minutes of forebrain ischemia (preconditioning ischemia). Some of them were subjected to a subsequent 5 minutes of forebrain ischemia 2 to 3 days after the preconditioning ischemia (double ischemia). Hippocampal slices were prepared from these gerbils subjected to the preconditioning or double ischemia, and field excitatory postsynaptic potentials were recorded from CA1 pyramidal neurons. Capacity for long-term potentiation triggered by tetanic stimulation (tetanic LTP) was transiently inhibited 1 to 2 days after the double ischemia but then recovered. Latency of anoxic depolarization was not significantly different between slices from preconditioned gerbils and those from sham-operated gerbils when these slices were subjected to in vitro anoxia. Postanoxic potentiation of N-methyl-D-aspartate (NMDA) receptor-mediated transmission (anoxic LTP) was inhibited in slices from gerbils 2 to 3 days after the preconditioning ischemia, whereas it was observed in slices from sham-operated gerbils and gerbils 9 days after the preconditioning ischemia. These results suggest that protection by induced tolerance is (1) not only morphologic but also functional, and (2) expressed in inhibiting postischemic overactivation of NMDA receptor-mediated synaptic responses.

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