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[Display omitted] Prenatal stress increases the risk of neurodevelopmental disorders. NMDA-type glutamate receptor (NMDAR) activity plays an important pathophysiological role in the cortico-hippocampal circuit in these disorders. We tested the hypothesis that transcription of NMDAR subunits is modified in the frontal cortex (FCx) and hippocampus after exposure to prenatal restraint stress (PRS) in mice. At 10 weeks of age, male PRS offspring (n = 20) and non-stressed controls (NS, n = 20) were treated with haloperidol (1 mg/kg), clozapine (5 mg/kg) or saline twice daily for 5 days, before measuring social approach (SOC). Saline-treated and haloperidol-treated PRS mice had reduced SOC relative to NS (P < 0.01), but clozapine-treated PRS mice had similar SOC to NS mice. These effects of PRS were associated with increased transcription of NMDAR subunits encoded by GRIN2A and GRIN2B genes in the hippocampus but not FCx. GRIN transcription in FCx correlated positively with SOC, but hippocampal GRIN transcription had negative correlation with SOC. The ratio of GRIN2A/GRIN2B transcription is known to increase during development but was lower in PRS mice. These results suggest that GRIN2A and GRIN2B transcript levels are modified in the hippocampus by PRS, leading to life-long deficits in social behavior. These data have some overlap with the molecular pathophysiology of schizophrenia. Similar to PRS in mice, schizophrenia, has been associated with social withdrawal, with increased GRIN2 expression in the hippocampus, and reduced GRIN2A/GRIN2B expression ratios in the hippocampus. These findings suggest that PRS in mice may have construct validity as a preclinical model for antipsychotic drug development. [ABSTRACT FROM AUTHOR]

Acute treatment with ketamine, an NMDA receptor antagonist, has been reported to be efficacious in treating depression. The goal of our study was to evaluate ketamine treatment in an animal model of another important psychiatric disease, post-traumatic stress disorder (PTSD). Fifty-eight male rats were initially divided into four groups: Control + Saline (CTRL + SAL), Control + Ketamine (CTRL + KET), PTSD + Saline (PTSD + SAL) and PTSD + Ketamine (PTSD + KET). To mimic PTSD we employed the inescapable footshock protocol. The PTSD animals were classified according to freezing behavior duration into “extreme behavioral response” (EBR) or “minimal behavioral response” (MBR). Afterwards, the glucose metabolism and BDNF were evaluated in the hippocampus, frontal cortex, and amygdala. Our results show that animals classified as EBR exhibited increased freezing behavior and that ketamine treatment further increased freezing duration. Glucose metabolism and BDNF levels showed no significant differences. These results suggest ketamine might aggravate PTSD symptoms and that this effect is unrelated to alterations in glucose metabolism or BDNF protein levels. [ABSTRACT FROM AUTHOR]

Taurine and alcohol has been popularly ingested through energy drinks. Reports from both compounds shows they are active on nervous system but little is known about the acute effect of these substances on the frontal cortex in an exercise approach. The aim of this study was to determine the effects of 0,6 ml dL −1 of ethanol (ET), 6 g of taurine (TA), and taurine with ethanol (TA + ET) intake on absolute alpha power (AAP) in the frontal region, before and after exercise. Nine participants were recruited, five women (22 ± 3 years) and four men (26 ± 5 years), for a counterbalanced experimental design. For each treatment, the tests were performed considering three moments: “baseline”, “peak” and “post-exercise”. In the placebo treatment (PL), the frontal areas showed AAP decrease at the post-exercise. However, in the TA, AAP decreased at peak and increased at post-exercise. In the ET treatment, AAP increased at the peak moment for the left frontal electrodes. In the TA + ET treatment, an AAP increase was observed at peak, and it continued after exercise ended. These substances were able to produce electrocortical activity changes in the frontal regions after a short duration and low intensity exercise. Left and right regions showed different AAP dynamics during peak and post-exercise moments when treatments were compared. [ABSTRACT FROM AUTHOR]

It is a point of controversy as to whether directed forgetting effects are a result of active inhibition or a change of context initiated by the instruction to forget. In this study we test the causal role of active inhibition in directed forgetting. By applying cathodal transcranial direct current stimulation (tDCS) over the right prefrontal cortex we suppressed cortical activity commonly associated with inhibitory control. Participants who underwent real brain stimulation before completing the directed forgetting paradigm showed no directed forgetting effects. Conversely, those who underwent sham brain stimulation demonstrated classical directed forgetting effects. We argue that these findings suggest that inhibition is the primary mechanism that results in directed forgetting costs and benefits. [ABSTRACT FROM AUTHOR]

Infralimbic cortex (IL) is proposed to suppress cocaine seeking after extinction, but whether the IL regulates the extinction and reinstatement of heroin-seeking behavior is unknown. To address this issue, the male SD rats were trained to self-administer heroin under a FR1 schedule for consecutive 14 days, then the rats underwent 7 daily 2 h extinction session in the operant chamber. The activation of IL by microinjection PEPA, an allosteric AMPA receptor potentiator into IL before each of extinction session facilitated the extinction responding after heroin self-administration, but did not alter the locomotor activity in an open field testing environment. Other rats were first trained under a FR1 schedule for heroin self-administration for 14 days, followed by 14 days of extinction training, and reinstatement of heroin-seeking induced by cues was measured for 2 h. Intra-IL microinjecting of PEPA at 15 min prior to test inhibited the reinstatement of heroin-seeking induced by cues. Moreover, the expression of GluR1 in the IL and NAc remarkably increased after treatment with PEPA during the reinstatement. These finding suggested that activation of glutamatergic projection from IL to NAc shell may be involved in the extinction and reinstatement of heroin-seeking. [ABSTRACT FROM AUTHOR]

Highlights: [•] Patients with vascular dementia had lower concentrations of Dynamin1 in cortical white matter. [•] The highest values of Dynamin1 were reported in patients with stroke without dementia. [•] The level of Dynamin1 in white matter correlates positively with cognitive scores. [Copyright &y& Elsevier]

Highlights: [&#x2022;] Significant increase in binding of two radio-ligands to the 5-HT2A receptor in transgene mice earlier shown to have reduced 5-HT levels. [&#x2022;] The change in 5-HT2A receptor binding is anatomical specific. [&#x2022;] No change in mGluR2/3 receptor binding in mice with higher levels of 5-HT2A receptor binding. [ABSTRACT FROM AUTHOR]

• We use MEG to study associations between cortical SG function and scores on SGI. • SG of right inferior frontal gyrus is correlated with perceptual modulation of SGI. • We suggest SG is an objective reflection of self-reported perceptual disturbance. Accumulated evidence has revealed that bilateral superior temporal gyrus (STG), inferior frontal gyrus (IFG), and inferior parietal lobule (IPL) are involved in the processes of sensory gating (SG). However, it remains unknown which neural correlate(s) of SG specifically reflect individuals' perceptual experiences, as measured by the Sensory Gating Inventory (SGI). Thus, this study aims to investigate the relationship of SGI with cortical SG-related regions. Furthermore, we examine whether SG hemispheric asymmetry exists, which is still an inconclusive issue. Twenty-two healthy young adults performed the auditory paired-stimulus paradigm during magnetoencephalographic recordings. SG of M50 and M100 was measured as ratios (S2/S1) and differences (S1–S2). They were also evaluated with SGI, which factored into three categories of Perceptual Modulation, Distractibility, and Over-Inclusion. SG in the STG, IFG, and IPL were compared between left and right hemispheres, and were used to determine the relationship with SGI. Only M100 SG differences (S1–S2) of the right IFG were significantly correlated with scores of Perceptual Modulation (partial r = -0.392, p = 0.040) and total SGI scores (partial r = -0.387, p = 0.041). However, we did not find significant lateralization of M50 SG and M100 SG in any studying region. The individual's perceptual experience is specifically related to electrophysiological SG function of the right IFG. [ABSTRACT FROM AUTHOR]

Abstract: Some central effects of cocaine administration seem to be related to angiotensin II (Ang II) or its metabolites. Nonetheless, it is still an open question whether or not the levels of angiotensin I-converting enzyme (ACE), the main Ang II generating enzyme, are modified by cocaine administration. To evaluate the effect of acute and subchronic cocaine administration on ACE activity and mRNA expression, male rats were randomly assigned to saline or cocaine group. Acute and subchronic cocaine administration induced a significant increase in ACE activity and mRNA expression in the frontal cortex and striatum but not in the hippocampus. These results suggest that some of the Ang II related effects of cocaine upon the central nervous system can be mediated by changes on the expression and activity of ACE in the striatum and frontal cortex. [Copyright &y& Elsevier]

Abstract: Transcranial direct current stimulation (tDCS) is one of the noteworthy noninvasive brain stimulation techniques, but the mechanism of its action remains unclear. With the aim of clarifying the mechanism, we developed a rat model and measured its effectiveness using fMRI. Carbon fiber electrodes were placed on the top of the head over the frontal cortex as the anode and on the neck as the cathode. The stimulus was 400- or 40-μA current applied for 10min after a baseline recording under an anesthetized condition. The 400-μA stimulation significantly increased signal intensities in the frontal cortex and nucleus accumbens. This suggests anodal tDCS over the frontal cortex induces neuronal activation in the frontal cortex and in its connected brain region. [Copyright &y& Elsevier]

Abstract: The transient receptor potential vanilloid type 1 (TRPV1) is a non-selective ligand-gated cationic channel. The distribution of TRPV1 mRNA in various regions of the brain has been successfully established. Methamphetamine (MAP) is a psychostimulant and a major drug of abuse in many parts of the world. The powerful rewarding properties of MAP are attributed to multiple pharmacological actions, but the mechanistic association between TRPV1 expression and MAP-induced drug addiction has not established. In the present study, we conducted a time-course analysis of TRPV1 mRNA levels in the frontal cortex, striatum, and hippocampus of mouse brain following repeated MAP (2mg/kg, i.p.) treatment. Our results demonstrate that expression of TRPV1 mRNA is significantly increased 1, 2, 6, 24, 48h, and 1 week after the last MAP treatment in the frontal cortex but not in the striatum or hippocampus. These data support a potential role for TRPV1 in the treatment of MAP-induced drug addiction. [Copyright &y& Elsevier]

Abstract: The long-term profile of direct current (DC) brain potential fluctuation has not yet been clarified. In this study, DC potentials were recorded in the frontal area of the cerebral cortex, referenced to the cerebellum, for 24h in freely moving rats under light control (dark period: 20:00–8:00h). Significant diurnal variation was observed, and the DC potential at the frontal area during the light period was more positive to the cerebellum than during the dark period. Amplitudes of DC potentials were negatively correlated with muscular activity. In addition, phasic negative shifts with durations of less than an hour were observed and were accompanied by muscular activation and delta wave suppression. These results suggest that the DC brain potentials fluctuate during the day and are related to changes in arousal level. [Copyright &y& Elsevier]

Abstract: Resting frontal electroencephalographic (EEG) alpha-asymmetry was measured in 16 participants to predict affective responses to musical stimuli. Three affective musical stimuli either expressing neutral, positive or negative mood were evaluated by the subjects concerning “expressed mood” and “level of enjoyment”. The results show that individuals with relatively higher alpha power over right frontal electrode sites rated all stimuli more positive than participants with relatively higher alpha power over left frontal electrode sites. On the “expressed mood” scale, the valence of the stimuli did not influence the difference between the ratings of left- and right-active individuals. On the “enjoyment” scale, the largest difference between the ratings of left- and right-active individuals emerged in the negative condition. The results are specific to the alpha frequency band. In line with previous studies, these results suggest that resting frontal alpha-asymmetry reflects a person''s predisposition to respond affectively. [Copyright &y& Elsevier]

Abstract: Neuroimaging studies have identified frontal lobe brain abnormalities in migraineurs. Neuropsychological investigations highlighted frontal lobe related cognitive impairments in migraineurs, including working memory and executive function deficits. The relationship between brain anatomy and cognitive function in migraine, however, is unclear. The aim of this study was to simultaneously investigated cortex structure and executive function (EF) in patients with migraine and control subjects. Thus, we assessed grey matter (GM) density in 25 adult patients with migraine, compared to age and sex-matched control subjects, using magnetic resonance imaging (MRI) and voxel-based-morphometry (VBM), and we measured EF in the same population, employing three EF tasks of the Maudsley attention and response suppression (MARS) battery. Migraineurs, compared to control subjects, showed decreased frontal and parietal lobe GM density and slower response time to task set-shifting and, the delayed response time correlated significantly with reduced GM density of the frontal lobes in migraineurs. Frontal and parietal lobe abnormalities in migraineurs could be an underlying cause of significantly slower response time during cognitive set-shifting. [Copyright &y& Elsevier]

Abstract: Several reports have suggested a role for mitochondrial dysfunction in the pathophysiology of bipolar disorder and schizophrenia. We have focused on the relationship between deleted mitochondrial DNA (mtDNA) and bipolar disorder. To investigate this relationship, we developed a methodology for quantification of the common 4977-bp deletion of mtDNA based on real-time polymerase chain reaction with SYBR Green. In this study, we assessed accumulation of the common deletion in postmortem frontal cortex from 147 individuals (48 controls, 49 patients with bipolar disorder, 50 patients with schizophrenia). We demonstrated age-dependent accumulation of the common deletion of mtDNA (p =1.09E−10). Females showed significantly higher accumulation of the deletion than did males (p =0.002). There was no significant association between accumulation and the two studied major mental disorders in the frontal cortex (p >0.2). However, there was no statistically significant correlation between the common deletion and aging in female patients with bipolar disorder (p =0.133), and no significant sex difference in patients with bipolar disorder (p =0.509). These results indicate that aging and sex have effect on accumulation of the common deletion of mtDNA in the prefrontal cortex depending on the diagnosis. [Copyright &y& Elsevier]

Abstract: Pyrrolidon carboxypeptidase (Pcp) is an omega peptidase that removes pyroglutamyl N-terminal residues of peptides such as thyrotrophin-releasing hormone (TRH), which is one of the neuropeptides that has been localized into many areas of the brain and acts as an endogenous neuromodulator of several parameters related to ethanol (EtOH) consumption. In this study, we analysed the effects of chronic EtOH intake on Pcp activity on mouse frontal cortex synaptosomes and their corresponding supernatant under basal and K+-stimulated conditions, in presence and absence of calcium (Ca2+) to know the regulation of Pcp on TRH. In basal conditions, chronic EtOH intake significantly decreased synaptosomes Pcp activity but only in absence of Ca2+. However, supernatant Pcp activity is also decreased in presence and absence of calcium. Under K+-stimulated conditions, chronic EtOH intake decreased synaptosomes Pcp activity but only in absence of Ca2+, whereas supernatant Pcp activity was significantly decreased only in presence of Ca2+. The general inhibitory effect of chronic EtOH intake on Pcp activity suggests an inhibition of TRH metabolism and an enhancement of TRH neurotransmitter/neuromodulator functions, which could be related to putative processes of tolerance to EtOH in which TRH has been involved. Our data may also indicate that active peptides and their degrading peptidases are released together to the synaptic cleft to regulate the neurotransmitter/neuromodulator functions of these peptides, through a Ca2+-dependent mechanism. [Copyright &y& Elsevier]

Abstract: In this study, we report the cortical sources of the gamma-band activity emitted during the auditory oddball paradigm using the adaptive beamformer algorithm and non-parametric permutation test and then compare them with those of the P3a and P3b components. The results of the gamma-band current sources revealed that the same gamma-band activities are in process during the rare target and novelty task. In the low (30–55Hz) gamma-band activity, the common sources were localized in the (inferior) anterior cingulate and adjacent inferior frontal cortex. In the high (65–85Hz) gamma-band activity, the generator was represented in the superior frontal cortex. On the other hand, the P3a and P3b generators showed widespread distributions including the well-known fronto-parietal network [J. Polich, Theoretical overview of P3a and P3b, in: J. Polish (Ed.), Detection of Change: Event-Related Potential and fMRI Findings, Kluwer Academic Press, Boston, 2003, pp. 83–98]. In conclusion, the same frontal generators of gamma-band activities in the present study may be associated with the functions of attentional control for the binding of consecutive cognitive stages corresponding to earlier P3a and later P3b components, which have distinct source distributions except for some overlaps. [Copyright &y& Elsevier]

Abstract: N-Ethylmaleimide sensitive factor (NSF) is a presynaptic protein that has been suggested to be differentially expressed in the cortex of schizophrenic subjects through both high-throughput proteomic and genomic screening studies. Thus, to expand upon these studies we measured NSF using Western blotting in four regions of the cortex (BA9, 10, 40 and 46), in a cohort comprising 20 schizophrenic subjects, 8 bipolar I disorder subjects, and 20 control subjects. There was no significant difference in NSF levels between diagnostic cohorts in any of the four cortical regions. These findings highlight the importance of validating findings from high-throughput screening studies and do not support changes in cortical NSF as being of significance in schizophrenia or bipolar 1 disorder. [Copyright &y& Elsevier]

Abstract: We have attempted to determine the effects of electroconvulsive shock (ECS) on protein phosphatase 2A (PP2A) in the frontal cortices of rats. PP2A exhibited a 30% increase in activity immediately after ECS treatment. Immunoblot analysis revealed that phosphorylation signals, including protein kinase B (Akt/PKB), glycogen synthase kinase-3β (GSK-3β), and cyclic adenosine monophosphate response element binding protein (CREB) were reduced immediately after ECS treatment. When an additional ECS was administered after the activation of these kinases, the immediate reactivation of PP2A overrode the kinase activity. ECS induces transient PP2A activation prior to kinase activation, and this pattern of activity may induce the biphasic phosphorylation of substrate proteins. [Copyright &y& Elsevier]

Pilocarpine-induced status epilepticus (SE) is an useful model to study the involvement of neurotransmitter systems as epileptogenesis modulators. Some researches have shown that pharmacological manipulations in dopaminergic, serotonergic, and noradrenergic systems alter the occurrence of pilocarpine-induced SE. The control group was treated with 0.9% saline (control group, s.c.). Another group of rats received pilocarpine (400mg/kg, s.c.) and both groups were sacrificed 24h after the treatment. This work was performed to determine the alterations in monoamine levels (dopamine (DA), serotonin (5-HT) and norepinephrine (NE)) and their metabolites (3,4-hydroxyphenylacetic acid (DOPAC), homovanilic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA)) after pilocarpine-induced SE in hippocampus and frontal cortex of adult rats. The monoamines and their metabolites were determined by reverse-phase high-performance liquid chromatography with electrochemical detection. DA and 5-HIAA concentrations were not altered in the hippocampus of the pilocarpine group, but in the same group the 5-HT (160%), DOPAC (316%) and HVA (21%) levels increased, whereas, the NE (47%) content declined. For the frontal cortex determinations, there was an increase of 20 and 72% in DA and DOPAC levels, respectively, and a decrease in NE (32%), 5-HT (33%) and 5-HIAA (19%) concentrations, but HVA content remained unaltered. These results indicate that pilocarpine-induced SE can alter monoamine levels in different ways depending on the brain area studied, suggesting that different mechanisms are involved. [Copyright &y& Elsevier]

The present study examines the influence of maternal pineal gland on the frontal cortex, striatal and testicular concentrations of the tachykinins, neurokinin A (NKA) and substance P (SP). Control, pinealectomized (PIN-X) and PIN-X plus melatonin-treated (PIN-X + MEL) mother rats were prepared. Male offspring rats were studied at 21, 31 and 60 days of age, during the four seasons of the year. In control-offspring tachykinin concentrations in frontal cortex were found at their highest levels in 21-day-old rats with a moderate decrease up to 60 days of age. This developmental pattern was season-dependent, observed only during summer and fall. Maternal PIN-X or PIN-X + MEL resulted in alterations in the offspring, showing during spring and summer significantly higher concentrations (P < 0.01) and during fall significantly lower concentrations of tachykinins in the frontal cortex (P < 0.05, P < 0.01) as compared to control-offspring. The tachykinin concentration in the striatum of control-offspring showed no major modifications throughout the ages studied in the four seasons of the year. With very few exceptions, PIN-X- and PIN-X + MEL did not alter tachykinin concentrations in striatum. Testicular SP concentrations showed a decrease from 21 to 60 days of age. PIN-X or PIN-X + MEL only caused minor and inconsistent modifications in testicular SP levels. In conclusion, our data clearly indicate for the first time that the maternal pineal gland participates in the regulation of the postnatal tachykinin development in some areas of the central nervous system. This effect was more evident in the frontal cortex than in the striatum and testes. [Copyright &y& Elsevier]

Social behaviour is the basis of one of the most generally accepted independent dimensions of personality. The purpose of the present study was to find out whether the social activity of individual rats, expressed in the social interaction test of anxiety, is consistent, and associated with monoamine levels. Four social interaction tests with 10 days intervals were carried out in 20 rats, and the animals were decapitated 4 days after the last test. There was no consistent correlation between performances in single tests, but the social interaction time in each test correlated strongly with the mean values of social activity in all or the other three tests. Social interaction time of rats correlated moderately but significantly with their partner’s social activity in the test. The average social interaction time correlated strongly with 5-HIAA levels in the frontal cortex (r=-0.67, P<0.01). Neither exposure of rats singly to the social interaction test box nor the test procedure had any effect on monoamine levels. When animals were decapitated immediately after a single social interaction test, there was a negative correlation between the social interaction time and 5-HIAA and 5-HT levels in the septum, but not in the frontal cortex or hippocampus. Thus, social behaviour is a stable trait, expression of which depends in part upon the partner’s social behaviour. This trait is negatively associated with 5-HT metabolism in the frontal cortex. Social activity of rats in a particular test situation may rather be related to 5-HT metabolism in the septum. [Copyright &y& Elsevier]

Glycosylation influences the biological activity of proteins and affects their folding and stability. Because aberrant glycosylation is associated with Alzheimer’s disease (AD), we applied proteome analysis together with Pro-Q Emerald 300 glycoprotein staining to investigate changes in glycosylated cytosolic proteins in AD and control brain. Frontal cortex proteins from 10 AD patients and 7 non-demented controls were subjected to separation by two-dimensional gel electrophoresis and subsequently stained with carbohydrate-specific Pro-Q Emerald 300 dye. Changes in glycosylation of separated proteins were quantified, and proteins of interest identified by mass spectrometry. Approximately 30% of all detectable proteins in the human frontal cortex appeared glycosylated, including heat shock cognate 71 stress protein and beta isoform of creatine kinase. The glycosylation of collapsin response mediator protein 2 (CRMP-2) and an unknown protein was reduced in AD, while the glycosylation of glial fibrillary acidic protein was increased. CRMP-2 regulates the assembly and polymerization of microtubules and is associated with neurofibrillary tangles in AD. Aberrant glycosylations in AD may help understand the mechanisms of neurodegenerative diseases. [Copyright &y& Elsevier]

Affective disorders are more common in women. The forced swim test acts like a depressive stimulus. Hippocampus and frontal cortex 5-HT1A receptors of female and male Wistar rats subjected to the forced swim test were compared with a sham group. The forced swim test diminishes (P<0.05) the hippocampus 3H-8OH-DPAT bound in the female rats (184±16 fmol/mg protein) with respect to the male rats (309±41 fmol/mg protein) and to the female sham rats (255±20 fmol/mg protein). The forced swim test increases the frontal cortex 5-HT1A receptors in the female rats with respect to the female sham group (40.4±5 versus 24.7±4 fmol/mg protein, P<0.05). An increased sensibility of the 5-HT1A receptors to depressive-stimulus may be one mechanism underlying the higher prevalence of depression in female. [Copyright &y& Elsevier]

The noradrenergic innervation of the frontal cortex and the hypothalamus arises from different brainstem nuclei and neurones projecting to these two brain regions differ topographically and morphologically. In the present study, we investigated whether there is a difference in noradrenaline clearance in these two brain areas using dual-probe microdialysis in freely-moving rats. Noradrenaline clearance was determined simultaneously in each brain area by measuring the noradrenaline extraction fraction using the ‘No Net Flux’ method, with both brain regions perfused with the same solutions. The noradrenaline extraction fraction was greater in the frontal cortex than in the hypothalamus (72 and 54%, respectively). This finding suggests that the processes involved in noradrenaline clearance, especially uptake, are more efficient in the former brain area, which could explain the differences in the increase in noradrenaline efflux when these brain areas are challenged with drugs that alter the function of the central nervous system. [Copyright &y& Elsevier]

The effect of reboxetine on norepinephrine (NE) efflux in the frontal cortex of freely moving rats has been studied using in vivo microdialysis. Reboxetine was administered either by injection (10 and 30 mg/kg i.p.) or directly to the frontal cortex via the dialysis probe (10 and 100 μM). To further elucidate the mechanism of action of reboxetine in this region yohimbine (10 μM) was co-infused with reboxetine via the frontal cortex probe. Both routes of administration of reboxetine resulted in a drug-induced, dose-dependent decrease in frontal cortex NE efflux. This effect was reversed following co-infusion of yohimbine, which has been shown to possess both α2-adrenoceptor antagonist and 5-HT1A agonist properties. [Copyright &y& Elsevier]

Repetitive transcranial magnetic stimulation (TMS) for 1 s at 4 Hz and 150% of the individual motor threshold was applied to primary motor cortex and adjacent cortical regions where no motor response could be produced. The hemodynamic reaction was measured using an event-related functional magnetic resonance setup. While all volunteers showed a typical signal increase beneath the coil during motor cortex stimulation, no consistent signal changes were present during frontal or parietal stimulation apart from activation of auditory cortex. The results suggest that neuronal stimulation by TMS is followed by an inhibitive phase that compensates for the effect of an initial neuronal activation. It is further concluded that the signal increases during motor cortex fit a sensory feedback from the moving body parts. [Copyright &y& Elsevier]

Pretreatment with DSP-4, a neurotoxin highly selective for the locus coeruleus (LC) noradrenergic projections, 2 weeks before in vivo microdialysis in conscious rats had no effect on baseline extracellular dopamine (DA) levels in the nucleus accumbens shell, but reduced dose-dependently the dopamine response to depolarisation induced by 50 mM KCl. DA metabolism in the frontal cortex, as measured ex vivo, was increased in animals treated with a low (10 mg/kg) but not with a high dose (50 mg/kg) of DSP-4, possibly indicating an increased sensitivity to stress in these animals and thus suggesting differential regulation of DA in the forebrain by the LC lesions. The reduced DA release potential in the nucleus accumbens after DSP-4 treatment suggests that weakening of the LC input to DA nerve cells contributes to motivational deficits. [Copyright &y& Elsevier]

The effect of partial isomerization of dietary α-linolenic acid on the monoaminergic neurotransmitters in piglets was studied. After feeding the animals for 14 days with diets containing or not trans α-linolenic acid, neurotransmitters related to the monoaminergic function were quantified in the frontal cortex and in the hippocampus. The partial isomerization of dietary α-linolenic acid resulted in increasing endogenous monoamine levels in the frontal cortex (+55% for dopamine) and was related to a very low incorporation of trans polyunsaturated fatty acids. However, feeding animals with a diet in which the imbalance generated by the isomerization of α-linolenic acid was corrected succeeded in reducing the levels of monoamine in the frontal cortex but not in the hippocampus. These results suggest that the dietary trans fatty acids may act on the endogenous neurotransmitter levels during the brain development. Further work is needed to clarify the molecular mechanisms involved. [Copyright &y& Elsevier]

S-adenosyl-l-methionine (SAM) has shown efficacy in speeding the onset of the antidepressant effect of imipramine in depressed patients. This effect may be related to their interactions at the serotonin1A (5-HT1A) receptors. Acute imipramine up-regulated the frontal cortex 5-HT1A receptors (Bmax, 51.5±8.4 fmol/mg protein) vs. saline (Bmax, 27.5±5.9 fmol/mg protein), and did not show antidepressant effect. Acute SAM and imipramine+SAM did not modify frontal cortex 5-HT1A receptors, and showed antidepressant effects (decrease of the immobility response of 26%, P<0.01; and 47%, P<0.001) vs. saline. All the chronic treatments showed antidepressant effects and up-regulated the hippocampus 5-HT1A receptors. SAM prevents the 5-HT1A receptor up-regulation induced by acute imipramine in the frontal cortex. This mechanism may contribute to imipramine''s antidepressant effect. [Copyright &y& Elsevier]

Abstract: In the present study we investigated the alterations on choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities in rat striatum and frontal cortex caused by pilocarpine-induced seizures. Wistar rats were treated with 0.9% saline (i.p., control group), with the association of 0.9% saline (i.p.) plus pilocarpine (400mg/kg, i.p.), 30min before of administration of saline (pilocarpine group). After the treatments all groups were observed for 1h. The ChAT and AChE activities were measured using spectrophotometric methods and the results compared to values obtained from saline-treated animals. In pilocarpine group was observed a significantly decreases in ChAT and AChE activities in striatum and frontal cortex of adult rats, when compared to control group. Results showed that during acute phase of seizures striatal and frontal cortex ChAT and AChE activities are diminished. Our findings suggest that seizures caused cognitive dysfunction and decreases of ChAT and AChE activities that might be related, at least in part, to the neurological problems presented by epileptic patients. [Copyright &y& Elsevier]

In the brain of a patient with Alzheimer''s disease, beta amyloid peptide (Aβ) is thought to be taken up by glial cells such as astrocyte and microglia to be degraded. However, it is unclear whether the Aβ is absorbed by astrocyte or microglia. The purpose of our study is to determine which type of glial cell, astrocyte or microglia, can take up Aβ. Beta amyloid 1-40 (Aβ1-40) was directly infused into the frontal cortex or hippocampus for 14 days. Dual-labeling immunohistochemistry for Aβ1-40 with an astrocytic (GFAP) or microglial (CD11b) marker was performed to examine co-localization of Aβ1-40 and glial markers. In the Aβ1-40 infused site, immunoreactivity of Aβ1-40 was observed only in astrocytes, not in microglia. In addition, Aβ40-1, a reverse peptide of Aβ1-40, was not taken up by astrocytes. These results suggested that the astrocyte-specific uptake of Aβ occurred in the rat brain. [Copyright &y& Elsevier]

The antidepressive action of electroconvulsive shock (ECS) is thought to involve the alteration in serotonin (5-HT) neurotransmission, including the increase in 5-HT release and uptake. In our previous study, 5-HT transporter (5-HTT) mRNA expression was decreased after single and repetitive ECS in rat raphe nucleus. In the present study, we investigated the effects of single and repetitive ECS on the protein levels of 5-HTT in the frontal cortex, hippocampus and raphe nucleus of rat brain using quantitative Western blot analysis. Single ECS did not alter 5-HTT protein expression in any brain regions examined. Repetitive ECS stably increased 5-HTT protein in the frontal cortex, but not in the hippocampus and raphe nucleus. Because ECS is known to facilitate the release of neurotransmitters, our results suggest that the increased 5-HTT protein expression in the frontal cortex might be a compensatory change against the enhanced 5-HT release by ECS in presynaptic terminals. [Copyright &y& Elsevier]