Daniela Řípová - Academia.edu (original) (raw)
Papers by Daniela Řípová
Neuro endocrinology letters, 2014
Toxoplasma gondii, the protozoan parasite infecting about 30% population worldwide, is suspected ... more Toxoplasma gondii, the protozoan parasite infecting about 30% population worldwide, is suspected to be the etiological agent of certain form of schizophrenia disease. Toxoplasma is known to change levels of certain neurotransmitters, cytokines and several hormones in both infected animals and humans. A common feature of toxoplasmosis and schizophrenia is a disorder of immune system. Here we studied the levels of five neuro- and immunomodulatory steroids, selected hormones and lipids in sera of 173 schizophrenia patients. Toxoplasma infected schizophrenia patients expressed only insignificantly lower concentration of neuro- and immunomodulatory DHEA metabolites. Infected women had higher concentration of glucose while infected men had higher concentration of cholesterol and LDL cholesterol. No significant effect of human cytomegalovirus infection on the concentration of the above parameters was observed. The difference in the concentration of DHEA metabolites faded with the decrease ...
We measured the length of the pyramidal neurons in the cortical layer III in four subregions of t... more We measured the length of the pyramidal neurons in the cortical layer III in four subregions of the planum temporale (transitions into superior temporal gyrus, Heschl's gyrus, insular cortex, and Sylvian fissure) in control group and Alzheimer disease patients. Our hypothesis was that overall length of the pyramidal neurons would be smaller in the Alzheimer disease group compared to controls and also there would be right-left asymmetry in both the control and Alzheimer disease groups. We found pyramidal neuron length asymmetry only in controls-in the transition into the Sylvian fissure-and the rest of the subregions in the control group and Alzheimer disease patients did not show size difference. However, control-Alzheimer disease group pyramidal neuron length comparison revealed (a) no length difference in superior temporal gyrus transition area, (b) reversal of asymmetry in the insular transition area with left insular transition significantly shorter in the Alzheimer disease ...
Journal of Alzheimer's disease: JAD
Background: Despite the physiological sequestration of amyloid-β (Aβ) peptides by various carrier... more Background: Despite the physiological sequestration of amyloid-β (Aβ) peptides by various carriers, interactions between peptides and protein tau appear to be pathological and involved in the development of Alzheimer's disease (AD). A recent study reported increased Aβ-tau interactions in the neurons of AD patients. Objective: We investigated the possibility that levels of Aβ-tau complexes in cerebrospinal fluid could be a prospective biomarker of AD, with greater sensitivity and specificity than Aβ1-42, tau, or phospho-tau individually. Methods: By means of ELISA, we estimated levels of the complexes in 161 people (non-demented controls, people with mild cognitive impairment (MCI), probable AD or other types of dementia). Results: We found significant reductions in levels in people with MCI due to AD (down to 84.5%) or with AD (down to 80.5%) but not in other types of dementia. The sensitivity of the new biomarker to AD was 68.6%, the specificity 73.3% (compared to controls) or...
A novel series of 7-methoxytacrine (7-MEOTA)-donepezil like compounds was synthesized and tested ... more A novel series of 7-methoxytacrine (7-MEOTA)-donepezil like compounds was synthesized and tested for their ability to inhibit electric eel acetylcholinesterase (EeAChE), human recombinant AChE (hAChE), equine serum butyrylcholinesterase (eqBChE) and human plasmatic BChE (hBChE). New hybrids consist of a 7-MEOTA unit, representing less toxic tacrine (THA) derivative, connected with analogues of N-benzylpiperazine moieties mimicking N-benzylpiperidine fragment from donepezil. 7-MEOTA-donepezil like compounds exerted mostly non-selective profile in inhibiting cholinesterases of different origin with IC50 ranging from micromolar to sub-micromolar concentration scale. Kinetic analysis confirmed mixed-type inhibition presuming that these inhibitors are capable to simultaneously bind peripheral anionic site (PAS) as well as catalytic anionic site (CAS) of AChE. Molecular modeling studies and QSAR studies were performed to rationalize studies from in vitro. Overall, 7-MEOTA-donepezil like derivatives can be considered as interesting candidates for Alzheimer's disease treatment.
PLoS ONE, 2014
In clinical practice as well as in many volumetric studies we use different reorientations of the... more In clinical practice as well as in many volumetric studies we use different reorientations of the brain position towards x and y axis on the magnetic resonance imaging (MRI) scans. In order to find out whether it has an overall effect on the resulting 2D data, manual hippocampal area measurements and rotation variability of the brain (in two reoriented axes) and the skull were performed in 23 Alzheimer's disease patients and 31 healthy controls. After the MRI scanning, native brain scans (nat) were reoriented into the two different artificial planes (anterior commissure-posterior commissure axis (AC-PC) and hippocampal horizontal long axis (hipp)). Hippocampal area and temporal horn of the lateral ventricle was measured manually using freeware Image J program. We found that 1) hippocampal area of nat images is larger compared to hipp images, area of the nat images is equal to the AC-PC images and area of the hipp images is smaller compared to AC-PC images, 2) hippocampal area together with the area of the temporal horn for nat images is larger compared to hipp images, area of the hipp images is smaller compared to the AC-PC images and area of the nat images is smaller compared to the AC-PC images. The conclusion is that the measured area of the hippocampus in the native MRI is almost the same as the area of MRI reoriented only into the AC-PC axis. Therefore, when performing 2D area studies of the hippocampus or in the clinical practice we recommend usage of not-reoriented MRI images or to reorient them into the AC-PC axis. Surprising finding was that rotation of both AC-PC and hipp line towards x-axis among patients varies up to 35° and the same is true for the skull rotation so that it is not only a matter of the brain position.
Neurochemical Research, 2012
Amyloid β peptides appear to play a role in physiological processes; however, they are also invol... more Amyloid β peptides appear to play a role in physiological processes; however, they are also involved in the pathogenesis of Alzheimer disease. Their actions under normal conditions are probably mediated by soluble monomeric L-isoforms at low concentrations, perhaps via highly specific interactions. On the contrary, toxic effects of aggregated natural L-isoforms/synthetic D-isoforms on membranes are very similar, but synthetic reverse/random L: -isoforms without pronounced aggregation properties are not toxic. Our previous work reported interactions of non-aggregated/aggregated L-isoforms of amyloid β peptides 1-40/1-42 with racemic 24-hydroxycholesterol. In this study, stereospecificity in the interactions of natural 24(S)hydroxycholesterol (cerebrosterol) or synthetic 24(R)hydroxycholesterol with soluble fragment 1-40 was evaluated by means of an in vitro test based on increased vulnerability of the hemicholinium-3 sensitive high-affinity choline uptake system in rat hippocampal cholesterol-depleted synaptosomes to the actions of amyloid β; computational simulations were also performed. Our results suggest that: (1) 24(S)hydroxycholesterol interacts with L-peptide 1-40 but not with the reverse L-peptide 40-1, (2) 24(R)hydroxycholesterol does not interact with L-peptide 1-40 or reverse 40-1, and (3) both enantiomers can probably interact with D-peptide 1-40. Therefore, the binding of 24(S)hydroxycholesterol is not fully stereospecific and the interaction could not reflect a physiological mechanism. Data from the computational simulation indicate that the hydrophobic core of the amyloid β molecule interacts with the hydrophobic part of 24(S)hydroxycholesterol, but no hydrogen bonds with high stability were found. Using this procedure, globular amyloid β could retain 24(S)hydroxycholesterol and thus contribute to its pathological accumulation in the brains of patients with Alzheimer disease.
Neurochemical Research, 2008
Brains of Alzheimer disease patients in early stages of dementia contain an increased 24(S)-hydro... more Brains of Alzheimer disease patients in early stages of dementia contain an increased 24(S)-hydroxycholesterol (cerebrosterol)/cholesterol ratio when compared to controls. In this study, effects of amyloid b peptides and of racemic 24-hydroxycholesterol were evaluated in vitro on undepleted or cholesterol-depleted hippocampal synaptosomes of young and old rats via a high-affinity choline transport and membrane anisotropy measurements. Depletion of membrane cholesterol decreased the transport of [3H]choline, increased the specific binding of [3H]hemicholinium-3 and decreased membrane anisotropy. However, less alterations were found in old when compared to young brains. 500 nM nonaggregated peptides were ineffective but aggregated fragment 1-42 evoked marked drops in the transport and anisotropy values on depleted synaptosomes. 50 lM 24hydroxycholesterol inhibited choline transport on depleted synaptosomes but it did not influence membrane anisotropy. Peptides eliminated the actions of oxysterol on choline carriers in young but not in old rats. On the other hand, oxysterol eliminated the effects of peptides on membrane anisotropy. Our study suggests a possible role of membrane cholesterol in the regulation of choline carriers and supports data reporting a protective role of membrane cholesterol against toxic effects of amyloid b peptides. Moreover, via Raman spectroscopy we demonstrate for the first time that peptides form a complex with 24hydroxycholesterol.
Journal of Immunological Methods, 2014
Tau protein in cerebrospinal fluid (CSF) is an important biomarker of Alzheimer's disease and som... more Tau protein in cerebrospinal fluid (CSF) is an important biomarker of Alzheimer's disease and some other brain diseases. Enzyme-linked immunosorbent assays (ELISAs) have been mostly used for quantification of tau and other biomarkers in CSF. However, these assays do not have sufficient sensitivity and dynamic range. In this study we tested the suitability of gold nanoparticles functionalized with tau-specific monoclonal antibody and oligonucleotide template for immunopolymerase chain reaction (Nano-iPCR) quantification of tau protein in human CSF samples and compared it with ELISA, either commercial or newly developed with tyramide signal amplification. Our data indicate that Nano-iPCR is superior in sensitivity and detection range to ELISA in tau protein detection.
Developmental Psychology, 2014
Alzheimer's & Dementia, 2011
It is well known that oligomeric/aggregated amyloid b peptides are a key player in the pathogenes... more It is well known that oligomeric/aggregated amyloid b peptides are a key player in the pathogenesis of Alzheimer's disease and that different nanoparticles influence oligomerization/aggregation processes in experiments in vitro. Our previous results demonstrated antiaggregation effects of magnetite nanoparticles in the case of protein lysozyme, however, they have yet to be supported by biological samples containing peptides/proteins preaggregated in vivo. In the study, Thioflavin T based fluorescence was evaluated on cerebrospinal fluid samples from people with Alzheimer's disease/multiple sclerosis and corresponding age-related controls using magnetite nanoparticles incubated for 24 h. Our results are as follows: (i) fluorescence of samples without nanoparticles was significantly higher in both older groups (old controls and people with Alzheimer's disease) than in those of younger (young controls and people with multiple sclerosis), (ii) nanoparticles did not markedly influence a fluorescence intensity in young people but eliminated it in both old groups; nevertheless, the effects of nanoparticles were significantly lower in patients with Alzheimer's disease then in the age-matched controls, and finally (iii) significant positive correlation was observed between fluorescence of samples without nanoparticles and levels of phospho-tau. Our results support studies reporting enhanced aggregation of different peptides/proteins occurring during normal aging and demonstrate for the first time that peptides/proteins preaggregated in vivo during Alzheimer's disease are more resistant to the antiaggregation effects of magnetite nanoparticles than those of age-matched controls. A significant correlation with phospho-tau levels indicate that the in vitro test with magnetite nanoparticles and Thioflavin T dye on cerebrospinal fluid could be sensitive to changes mediated by early Alzheimer's disease stages.
Pharmacology Biochemistry and Behavior, 2014
In the present study we investigated the potential antipsychotic effects of the mGlu2/3 agonist L... more In the present study we investigated the potential antipsychotic effects of the mGlu2/3 agonist LY379268 on changes in EEG power spectra and coherence in the ketamine model of psychosis. In order to use behaviorally active drug doses, experiments detecting changes in locomotor activity and sensorimotor gating were also conducted. In EEG experiments, adult male Wistar rats were injected with ketamine 30 mg/kg i.p. and LY379268 3 mg/kg i.p. Cortical EEG was recorded from twelve (2 × 6) electrodes placed homolaterally on each hemisphere. To avoid interference with the behavioral hyperactivity of ketamine challenge, the behavioral activity of animals was simultaneously registered at the time of recording. Subsequent power spectral and coherence analyses were assessed in epochs corresponding to behavioral inactivity. Analysis of segments with behavioral activity compared to inactivity was also performed. The effects of LY379268 3 mg/kg i.p. on the deficits in sensorimotor processing and on hyperlocomotion induced by ketamine were evaluated in the test of prepulse inhibition of acoustic startle reaction (PPI ASR) and in the open field. LY379268 reversed the ketamine-induced hyperlocomotion but had no effect on ketamine-induced PPI deficits. In EEG epochs corresponding to behavioral inactivity ketamine decreased the power in the delta band, induced a power increase in the high frequency bands and globally decreased EEG coherence. Pretreatment with the LY379268 completely reversed the ketamine-induced power increase in high frequency bands and had a partial effect on EEG coherence. LY379268 alone induced a decrease of beta, high beta and low-gamma power, and an increase in coherence in high frequency bands. Additional analysis revealed that behavioral activity increases power as well as coherence in most frequency bands. In conclusion, agonism of mGlu2/3 receptors was effective in reversing most of the changes induced by ketamine, however due to the lack of effectiveness on PPI deficits its potential antipsychotic properties remain disputable.
Neuro endocrinology letters, 2014
Toxoplasma gondii, the protozoan parasite infecting about 30% population worldwide, is suspected ... more Toxoplasma gondii, the protozoan parasite infecting about 30% population worldwide, is suspected to be the etiological agent of certain form of schizophrenia disease. Toxoplasma is known to change levels of certain neurotransmitters, cytokines and several hormones in both infected animals and humans. A common feature of toxoplasmosis and schizophrenia is a disorder of immune system. Here we studied the levels of five neuro- and immunomodulatory steroids, selected hormones and lipids in sera of 173 schizophrenia patients. Toxoplasma infected schizophrenia patients expressed only insignificantly lower concentration of neuro- and immunomodulatory DHEA metabolites. Infected women had higher concentration of glucose while infected men had higher concentration of cholesterol and LDL cholesterol. No significant effect of human cytomegalovirus infection on the concentration of the above parameters was observed. The difference in the concentration of DHEA metabolites faded with the decrease ...
We measured the length of the pyramidal neurons in the cortical layer III in four subregions of t... more We measured the length of the pyramidal neurons in the cortical layer III in four subregions of the planum temporale (transitions into superior temporal gyrus, Heschl's gyrus, insular cortex, and Sylvian fissure) in control group and Alzheimer disease patients. Our hypothesis was that overall length of the pyramidal neurons would be smaller in the Alzheimer disease group compared to controls and also there would be right-left asymmetry in both the control and Alzheimer disease groups. We found pyramidal neuron length asymmetry only in controls-in the transition into the Sylvian fissure-and the rest of the subregions in the control group and Alzheimer disease patients did not show size difference. However, control-Alzheimer disease group pyramidal neuron length comparison revealed (a) no length difference in superior temporal gyrus transition area, (b) reversal of asymmetry in the insular transition area with left insular transition significantly shorter in the Alzheimer disease ...
Journal of Alzheimer's disease: JAD
Background: Despite the physiological sequestration of amyloid-β (Aβ) peptides by various carrier... more Background: Despite the physiological sequestration of amyloid-β (Aβ) peptides by various carriers, interactions between peptides and protein tau appear to be pathological and involved in the development of Alzheimer's disease (AD). A recent study reported increased Aβ-tau interactions in the neurons of AD patients. Objective: We investigated the possibility that levels of Aβ-tau complexes in cerebrospinal fluid could be a prospective biomarker of AD, with greater sensitivity and specificity than Aβ1-42, tau, or phospho-tau individually. Methods: By means of ELISA, we estimated levels of the complexes in 161 people (non-demented controls, people with mild cognitive impairment (MCI), probable AD or other types of dementia). Results: We found significant reductions in levels in people with MCI due to AD (down to 84.5%) or with AD (down to 80.5%) but not in other types of dementia. The sensitivity of the new biomarker to AD was 68.6%, the specificity 73.3% (compared to controls) or...
A novel series of 7-methoxytacrine (7-MEOTA)-donepezil like compounds was synthesized and tested ... more A novel series of 7-methoxytacrine (7-MEOTA)-donepezil like compounds was synthesized and tested for their ability to inhibit electric eel acetylcholinesterase (EeAChE), human recombinant AChE (hAChE), equine serum butyrylcholinesterase (eqBChE) and human plasmatic BChE (hBChE). New hybrids consist of a 7-MEOTA unit, representing less toxic tacrine (THA) derivative, connected with analogues of N-benzylpiperazine moieties mimicking N-benzylpiperidine fragment from donepezil. 7-MEOTA-donepezil like compounds exerted mostly non-selective profile in inhibiting cholinesterases of different origin with IC50 ranging from micromolar to sub-micromolar concentration scale. Kinetic analysis confirmed mixed-type inhibition presuming that these inhibitors are capable to simultaneously bind peripheral anionic site (PAS) as well as catalytic anionic site (CAS) of AChE. Molecular modeling studies and QSAR studies were performed to rationalize studies from in vitro. Overall, 7-MEOTA-donepezil like derivatives can be considered as interesting candidates for Alzheimer's disease treatment.
PLoS ONE, 2014
In clinical practice as well as in many volumetric studies we use different reorientations of the... more In clinical practice as well as in many volumetric studies we use different reorientations of the brain position towards x and y axis on the magnetic resonance imaging (MRI) scans. In order to find out whether it has an overall effect on the resulting 2D data, manual hippocampal area measurements and rotation variability of the brain (in two reoriented axes) and the skull were performed in 23 Alzheimer's disease patients and 31 healthy controls. After the MRI scanning, native brain scans (nat) were reoriented into the two different artificial planes (anterior commissure-posterior commissure axis (AC-PC) and hippocampal horizontal long axis (hipp)). Hippocampal area and temporal horn of the lateral ventricle was measured manually using freeware Image J program. We found that 1) hippocampal area of nat images is larger compared to hipp images, area of the nat images is equal to the AC-PC images and area of the hipp images is smaller compared to AC-PC images, 2) hippocampal area together with the area of the temporal horn for nat images is larger compared to hipp images, area of the hipp images is smaller compared to the AC-PC images and area of the nat images is smaller compared to the AC-PC images. The conclusion is that the measured area of the hippocampus in the native MRI is almost the same as the area of MRI reoriented only into the AC-PC axis. Therefore, when performing 2D area studies of the hippocampus or in the clinical practice we recommend usage of not-reoriented MRI images or to reorient them into the AC-PC axis. Surprising finding was that rotation of both AC-PC and hipp line towards x-axis among patients varies up to 35° and the same is true for the skull rotation so that it is not only a matter of the brain position.
Neurochemical Research, 2012
Amyloid β peptides appear to play a role in physiological processes; however, they are also invol... more Amyloid β peptides appear to play a role in physiological processes; however, they are also involved in the pathogenesis of Alzheimer disease. Their actions under normal conditions are probably mediated by soluble monomeric L-isoforms at low concentrations, perhaps via highly specific interactions. On the contrary, toxic effects of aggregated natural L-isoforms/synthetic D-isoforms on membranes are very similar, but synthetic reverse/random L: -isoforms without pronounced aggregation properties are not toxic. Our previous work reported interactions of non-aggregated/aggregated L-isoforms of amyloid β peptides 1-40/1-42 with racemic 24-hydroxycholesterol. In this study, stereospecificity in the interactions of natural 24(S)hydroxycholesterol (cerebrosterol) or synthetic 24(R)hydroxycholesterol with soluble fragment 1-40 was evaluated by means of an in vitro test based on increased vulnerability of the hemicholinium-3 sensitive high-affinity choline uptake system in rat hippocampal cholesterol-depleted synaptosomes to the actions of amyloid β; computational simulations were also performed. Our results suggest that: (1) 24(S)hydroxycholesterol interacts with L-peptide 1-40 but not with the reverse L-peptide 40-1, (2) 24(R)hydroxycholesterol does not interact with L-peptide 1-40 or reverse 40-1, and (3) both enantiomers can probably interact with D-peptide 1-40. Therefore, the binding of 24(S)hydroxycholesterol is not fully stereospecific and the interaction could not reflect a physiological mechanism. Data from the computational simulation indicate that the hydrophobic core of the amyloid β molecule interacts with the hydrophobic part of 24(S)hydroxycholesterol, but no hydrogen bonds with high stability were found. Using this procedure, globular amyloid β could retain 24(S)hydroxycholesterol and thus contribute to its pathological accumulation in the brains of patients with Alzheimer disease.
Neurochemical Research, 2008
Brains of Alzheimer disease patients in early stages of dementia contain an increased 24(S)-hydro... more Brains of Alzheimer disease patients in early stages of dementia contain an increased 24(S)-hydroxycholesterol (cerebrosterol)/cholesterol ratio when compared to controls. In this study, effects of amyloid b peptides and of racemic 24-hydroxycholesterol were evaluated in vitro on undepleted or cholesterol-depleted hippocampal synaptosomes of young and old rats via a high-affinity choline transport and membrane anisotropy measurements. Depletion of membrane cholesterol decreased the transport of [3H]choline, increased the specific binding of [3H]hemicholinium-3 and decreased membrane anisotropy. However, less alterations were found in old when compared to young brains. 500 nM nonaggregated peptides were ineffective but aggregated fragment 1-42 evoked marked drops in the transport and anisotropy values on depleted synaptosomes. 50 lM 24hydroxycholesterol inhibited choline transport on depleted synaptosomes but it did not influence membrane anisotropy. Peptides eliminated the actions of oxysterol on choline carriers in young but not in old rats. On the other hand, oxysterol eliminated the effects of peptides on membrane anisotropy. Our study suggests a possible role of membrane cholesterol in the regulation of choline carriers and supports data reporting a protective role of membrane cholesterol against toxic effects of amyloid b peptides. Moreover, via Raman spectroscopy we demonstrate for the first time that peptides form a complex with 24hydroxycholesterol.
Journal of Immunological Methods, 2014
Tau protein in cerebrospinal fluid (CSF) is an important biomarker of Alzheimer's disease and som... more Tau protein in cerebrospinal fluid (CSF) is an important biomarker of Alzheimer's disease and some other brain diseases. Enzyme-linked immunosorbent assays (ELISAs) have been mostly used for quantification of tau and other biomarkers in CSF. However, these assays do not have sufficient sensitivity and dynamic range. In this study we tested the suitability of gold nanoparticles functionalized with tau-specific monoclonal antibody and oligonucleotide template for immunopolymerase chain reaction (Nano-iPCR) quantification of tau protein in human CSF samples and compared it with ELISA, either commercial or newly developed with tyramide signal amplification. Our data indicate that Nano-iPCR is superior in sensitivity and detection range to ELISA in tau protein detection.
Developmental Psychology, 2014
Alzheimer's & Dementia, 2011
It is well known that oligomeric/aggregated amyloid b peptides are a key player in the pathogenes... more It is well known that oligomeric/aggregated amyloid b peptides are a key player in the pathogenesis of Alzheimer's disease and that different nanoparticles influence oligomerization/aggregation processes in experiments in vitro. Our previous results demonstrated antiaggregation effects of magnetite nanoparticles in the case of protein lysozyme, however, they have yet to be supported by biological samples containing peptides/proteins preaggregated in vivo. In the study, Thioflavin T based fluorescence was evaluated on cerebrospinal fluid samples from people with Alzheimer's disease/multiple sclerosis and corresponding age-related controls using magnetite nanoparticles incubated for 24 h. Our results are as follows: (i) fluorescence of samples without nanoparticles was significantly higher in both older groups (old controls and people with Alzheimer's disease) than in those of younger (young controls and people with multiple sclerosis), (ii) nanoparticles did not markedly influence a fluorescence intensity in young people but eliminated it in both old groups; nevertheless, the effects of nanoparticles were significantly lower in patients with Alzheimer's disease then in the age-matched controls, and finally (iii) significant positive correlation was observed between fluorescence of samples without nanoparticles and levels of phospho-tau. Our results support studies reporting enhanced aggregation of different peptides/proteins occurring during normal aging and demonstrate for the first time that peptides/proteins preaggregated in vivo during Alzheimer's disease are more resistant to the antiaggregation effects of magnetite nanoparticles than those of age-matched controls. A significant correlation with phospho-tau levels indicate that the in vitro test with magnetite nanoparticles and Thioflavin T dye on cerebrospinal fluid could be sensitive to changes mediated by early Alzheimer's disease stages.
Pharmacology Biochemistry and Behavior, 2014
In the present study we investigated the potential antipsychotic effects of the mGlu2/3 agonist L... more In the present study we investigated the potential antipsychotic effects of the mGlu2/3 agonist LY379268 on changes in EEG power spectra and coherence in the ketamine model of psychosis. In order to use behaviorally active drug doses, experiments detecting changes in locomotor activity and sensorimotor gating were also conducted. In EEG experiments, adult male Wistar rats were injected with ketamine 30 mg/kg i.p. and LY379268 3 mg/kg i.p. Cortical EEG was recorded from twelve (2 × 6) electrodes placed homolaterally on each hemisphere. To avoid interference with the behavioral hyperactivity of ketamine challenge, the behavioral activity of animals was simultaneously registered at the time of recording. Subsequent power spectral and coherence analyses were assessed in epochs corresponding to behavioral inactivity. Analysis of segments with behavioral activity compared to inactivity was also performed. The effects of LY379268 3 mg/kg i.p. on the deficits in sensorimotor processing and on hyperlocomotion induced by ketamine were evaluated in the test of prepulse inhibition of acoustic startle reaction (PPI ASR) and in the open field. LY379268 reversed the ketamine-induced hyperlocomotion but had no effect on ketamine-induced PPI deficits. In EEG epochs corresponding to behavioral inactivity ketamine decreased the power in the delta band, induced a power increase in the high frequency bands and globally decreased EEG coherence. Pretreatment with the LY379268 completely reversed the ketamine-induced power increase in high frequency bands and had a partial effect on EEG coherence. LY379268 alone induced a decrease of beta, high beta and low-gamma power, and an increase in coherence in high frequency bands. Additional analysis revealed that behavioral activity increases power as well as coherence in most frequency bands. In conclusion, agonism of mGlu2/3 receptors was effective in reversing most of the changes induced by ketamine, however due to the lack of effectiveness on PPI deficits its potential antipsychotic properties remain disputable.