Neurochemical Methods Research Articles

Activation and Blockade of Serotonin-4 Receptors in the Lateral Habenula Produce Antidepressant Effects in the Hemiparkinsonian Rat

Background: The 5-hydroxytryptamine (5-HT) neurotransmitter system and lateral habenula (LHb) are involved in the regulation of depression, while the mechanisms remain to be clarified. Objectives: The effects and possible mecha-nism underlying activation or blockade of 5-HT₄ receptors (5-HT₄Rs) in the LHb in depression were investigated by behavioral and neurochemical methods based on a Parkinson’s disease (PD) rat model. Method: 6-Hydroxydopamine (6-OHDA) was injected unilaterally into the substantia nigra pars compacta to establish the PD rat model. The depressive-like behaviors were measured by the forced swimming test (FST) and sucrose preference test (SPT). The concentrations of dopamine (DA), noradrenaline (NA) and 5-HT in the related brain regions were measured by a neurochemical method. Results: The 6-OHDA lesions increased the immobility time in the FST and decreased the sucrose consumption in the SPT, suggesting the induction of depressive-like behaviors. Intra-LHb injection of BIMU-8 (5-HT₄R agonist) or GR113808 (5-HT₄R antagonist) produced antidepressant effects in the lesioned rats. Intra-LHb injection of BIMU-8 significantly increased the DA levels in the medial prefrontal cortex (mPFC) and ventral hippocampus (vHip), increased the 5-HT level in the mPFC and decreased the NA level in the vHip only in the lesioned rats, while intra-LHb injection of GR113808 changed DA, NA and 5-HT levels in the mPFC, LHb and vHip in both sham and the lesioned rats. Conclusions: All these results suggest that activation or blockade of the LHb 5-HT₄Rs produce antidepressant effects in the 6-OHDA-lesioned rats, which are related to the changes of monoamines in the limbic and limbic-related regions.

Development of Action Potential Waveform in Hippocampal CA1 Pyramidal Neurons

CA1 pyramidal neurons undergo intense morphological and electrophysiological changes from the second to third postnatal weeks in rats throughout a critical period associated with the emergence of exploratory behavior. Using whole cell current-clamp recordings in vitro and neurochemical methods, we studied the development of the somatic action potential (AP) waveform and some of the underlying channels in this critical period. At the third postnatal week, APs showed a more hyperpolarized threshold, higher duration and amplitude. Subthreshold depolarization broadened APs and depolarized their peak overshoots more pronouncedly in immature neurons (2 weeks old). These features were mimicked by pharmacologically blocking the fast-inactivating A-type potassium current (IA) and matched well with the higher concentrations of Kv4.2 and Kv4.3 and the lower concentrations of BK and Kv1.2 channels detected by Western blotting. Repetitive stimulation with high frequency trains (50 Hz) reproduced AP broadening associated to inactivation of the A-type current in immature cells. Moreover, repetitive firing showed changes in AP amplitude consistent with the inactivation of both sodium and potassium subthreshold currents, which resulted in higher AP amplitudes in the more immature neurons. We propose that maturation of AP waveform and excitability in this critical developmental period could be related to the onset of exploratory behaviors.

Involvement of the Dorsal Hippocampus 5-HT1A Receptors in the Regulation of Depressive-Like Behaviors in Hemiparkinsonian Rats

Background: Depression is one of the most common neuropsychiatric disturbances in Parkinson’s disease (PD), but its pathophysiology is not definite. Lines of evidence have indicated that the hippocampus and serotonin 1A (5-HT_1A) receptors are related to the regulation of depression. Objective:The purpose of the present study was to observe the effect of 5-HT_1A receptors in the dorsal hippocampus (dHIP) on PD-related depression in rats. Methods: Unilateral 6-hydroxydopamine lesioning of the medial forebrain bundle (MFB) was used to establish the hemiparkinsonian rat model. The effects of intra-dHIP injection of the 5-HT_1A receptor ­agonist 8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT) or antagonist WAY-100635 on depressive-like behaviors were observed in sucrose preference and forced swim tests in control and lesioned rats. Monoamine levels including dopamine (DA), 5-HT, and noradrenaline (NA) in depression-related brain regions were determined by a neurochemical method in all groups. Results: Behavioral results showed that MFB lesions induced depressive-like behaviors. Intra-dHIP injection of 8-OH-DPAT produced antidepressant effects, while WAY-100635 induced or increased the depressive-like behaviors in both control and the lesioned rats. Neurochemical results found that intra-dHIP injection of 8-OH-DPAT significantly increased DA and 5-HT levels in the medial prefrontal cortex (mPFC), lateral habenula (LHb), ventral hippocampus and amygdala in the lesioned group and decreased NA levels in the mPFC and LHb in the control group. Moreover, after injection of WAY-100635, NA levels in all these regions of the lesioned group were significantly increased. Conclusions: These findings suggest that hippocampal 5-HT_1A receptors regulate depression and PD-related depression by neurochemical mechanisms.

Interaction of dopamine, nitric oxide and testosterone in the brain system of motivational reinforcement in rats with alcohol dependence and under nitric oxide donator impact

The complex of neurophysiological methods (stereotaxic implantation of electrodes into brain structures, recording of electrical activity of the neocortex, hippocampus, hypothalamus, and nucleus accumbens) was applied to 65 laboratory male rats with models of chronic alcoholization (during 40 days of alcohol consumption in dose 1.25 g/kg body mass) and alcohol withdrawal during 2 days. The leading role of functional changes of electrogenesis in hippocampus, hypothalamus and nucleus accumbens has been revealed in rats being in states of alcohol dependence. The highest absolute spectral powers of oscillations of the β and Ѳ rhythms in the hippocampus and manifestations of generalized hypersynchronous activity with initiation in the hippocampus and hypothalamus were noted in rats under alcohol dependence. The paroxysmal pattern of activity on EEG of the structures of the limbico-neocortical system acquired an “explosive” character after alcohol withdrawal. The complex of neurochemical methods (detection of dopamine and testosterone concentration with enzymoimmunoassay and nitric oxide concentration with spectrophotometric analysis in the brain structures and serum) was carried out after 40 days of alcoholization as well as after 2 days of alcohol withdrawal. Decreased levels of testosterone and nitric oxide were identified in hypothalamus and hippocampus as well as testosterone in nucleus accumbens and serum. There were observed increased dopamine release in nucleus accumbens in response to latest dose of alcohol consumption and recovery of dopamine level after alcohol withdrawal. To the contrary, the dopamine content decreased in hypothalamus in the state of alcohol withdrawal. The five-time (twice a day) intranasal introduction of sodium nitroprusside repaired nitric oxide and testosterone levels in the brain structures of motivational reinforcement and suppressed seizure pattern on EEG but didn’t change testosterone concentration in serum. Obtained data are considered as one of the important aspects of interactions in the system of hormonal-neurotransmitter-metabolic regulatory mechanisms of motivational reinforcement under formation and suppression of alcohol dependence.

The antidepressant-like effect of trans-astaxanthin involves the serotonergic system.

The antidepressant-like effect of trans-astaxanthin, a compound present rich in algae, was evaluated through behavioral and neurochemical methods. Results showed that trans-astaxanthin treatment significantly decreased the immobility time in force swim test and tail suspension test, but did not influence locomotor activity. Trans-astaxanthin treatment did not effectively antagonize hypothermia and ptosis induced by reserpine. However, pre-treatment with para-chlorophenylalanine abolished the anti-immobility effect of trans-astaxanthin in force swim and tail suspension test. These results suggested that the mechanism of antidepressant-like effect of trans-astaxanthin may involve the serotonergic system, but not noradrenaline system. This hypothesis was confirmed by neurochemical assays which showed that trans-astaxanthin increased serotonin levels in the hippocampus, frontal cortex, striatum and hypothalamus. Furthermore, our data suggested that trans-astaxanthin decreased indoleamine 2, 3-dioxygenase activity in the hippocampus, frontal cortex and hypothalamus. Inhibition of indoleamine 2,3-dioxygenase activity subsequently decreased the kynurenine/tryptophan ratio and increased the serotonin/tryptophan ratio in these brain regions. Taken together, these findings indicate that the antidepressant-like effect of trans-astaxanthin involves the serotonergic system.

A microdialysis and enzymatic reactor sensing procedure for the simultaneous registration of online glutamate measurements at high temporal resolution during epileptiform activity.

Glutamate measurement in microdialysis samples has primarily been determined using HPLC methods, and several attempts have been made to establish a relationship between this neurotransmitter and EEG activity during altered brain function, such as epilepsy. However, classic microdialysis methods lack high temporal resolution. In this study, a new alternative is proposed to improve the time resolution and thus obtain a better understanding of the dynamics of Glu and its relationship with epileptiform activity. A new setup was designed to measure Glu online in microdialysates using enzymatic reactors and fluorescence detection. In this study, we performed EEG recordings and Glu measurements simultaneously in the hippocampus to establish their relationship with the epileptiform events that are induced by pentylenetetrazole in intact and epileptic rats. Basal Glu levels in intact and animals with spontaneous seizures were not significantly different. However, a significant increase in Glu levels was detected during the first pentylenetetrazole-induced seizure in both groups. EEG analysis showed that the amplitude of epileptiform activity was higher in rats with spontaneous seizures and that the frequency of this activity did not change. The results showed that this method can be used to determine Glu changes at high temporal resolution and that these changes can be related to seizure activity. In addition, this method can also be used to measure other neurotransmitters that generate fluorescent derivatives. Moreover, this new technique has the following advantages compared with classical neurochemical methods: easy setup, low training requirements, no need for separation, rapidity, and the experimental data can be obtained and analysis performed in a single session.

A Rat Model of Alzheimer's Disease Based on Abeta42 and Pro-oxidative Substances Exhibits Cognitive Deficit and Alterations in Glutamatergic and Cholinergic Neurotransmitter Systems.

Alzheimer’s disease (AD) is one of the most serious human, medical, and socioeconomic burdens. Here we tested the hypothesis that a rat model of AD (Samaritan; Taconic Pharmaceuticals, USA) based on the application of amyloid beta42 (Abeta42) and the pro-oxidative substances ferrous sulfate heptahydrate and L-buthionine-(S, R)-sulfoximine, will exhibit cognitive deficits and disruption of the glutamatergic and cholinergic systems in the brain. Behavioral methods included the Morris water maze (MWM; long-term memory version) and the active allothetic place avoidance (AAPA) task (acquisition and reversal), testing spatial memory and different aspects of hippocampal function. Neurochemical methods included testing of the NR1/NR2A/NR2B subunits of NMDA receptors in the frontal cortex and CHT1 transporters in the hippocampus, in both cases in the right and left hemisphere separately. Our results show that Samaritan rats™ exhibit marked impairment in both the MWM and active place avoidance tasks, suggesting a deficit of spatial learning and memory. Moreover, Samaritan rats exhibited significant changes in NR2A expression and CHT1 activity compared to controls rats, mimicking the situation in patients with early stage AD. Taken together, our results corroborate the hypothesis that Samaritan rats are a promising model of AD in its early stages.

Analgesic effect of ferulic acid on CCI mice：behavior and neurobiological analysis

To study the analgesic effect of chronic administration with ferulic acid, and preliminarily discuss its mechanism. Thermal hyperalgesia and mechanical allodynia tests were conducted to observe the analgesic effect of chronic administration with ferulic acid on CCI mice. The neurochemical detection method was applied to observe the effect chronic administration with ferulic acid on monoamine neurotransmitter and monoamine oxidase activity. Compared with the normal group, CCI mice showed notable reduction in heat sensation and nociceptive threshold in and mechanical allodynia. Ferulic acid (10, 20, 40 and 80 mg x kg(-1), po) could significantly reverse the situations. In an in-depth study, we found that the reason for these results was that ferulic acid was dose-dependent in increasing 5-HT and NE levels in hippocampus, frontal cortex and amygdale and could inhibit MAO-A activity in mouse brains. These results showed that ferulic acid has the analgesic effect. Its mechanism may be related to the inhibition of monoamine oxidase activity and the increase in monoamine neurotransmitter in mouse brains.

The antidepressant-like effect of bacopaside I: Possible involvement of the oxidative stress system and the noradrenergic system

In the present study, the antidepressant-like effect of bacopaside I, a saponin compound present in the Bacopa monniera plant, was evaluated by behavioral and neurochemical methods. Bacopaside I (50, 15 and 5mg/kg) was given to mice via oral gavage for 7 successive days. The treatment significantly decreased the immobility time in mouse models of despair tests, but it did not influence locomotor activity. Neurochemical assays suggested that treatment by bacopaside I (50, 15 and 5mg/kg) improved brain antioxidant activity to varying degrees after the behavioral despair test. Bacopaside I (15 and 5mg/kg) significantly reversed reserpine-induced depressive-like behaviors, including low temperature and ptosis. Conversely, bacopaside I did not affect either brain MAO-A or MAO-B activity after the behavioral despair test in mice. Additionally, 5-hydroxytryptophan (a precursor of 5-serotonin) was not involved in the antidepressant-like effect of bacopaside I. These findings indicated that the antidepressant-like effect of bacopaside I might be related to both antioxidant activation and noradrenergic activation, although the exact mechanism remains to be further elucidated.

Evidências neuroquímicas e comportamentais do efeito ansiogênico da deltametrina em ratos

Pyrethroid insecticides are extensively used for pest control around the house, flea prevention for pets, and plant sprays for the home and in agriculture. Deltamethrin (DTM) is a Type II pyrethroid insecticide used to control a variety of insects in agriculture and domestic environments. The present study investigated the possible anxiogenic effects of DTM (1, 3, and 10 mg/kg) in rats using behavioral and neurochemical methods. We assessed general locomotor activity and behavior in the elevated plus maze and open field test. Striatal and hippocampal neurotransmitter and metabolite levels were also measured. DTM (i) reduced locomotion and rearing frequency, (ii) slightly increased the duration of immobility, (iii) reduced the time engaged in social interaction, (iv) reduced the percentage of entries into and time spent on the open arms of the elevated plus maze, (v) reduced the number of center crossings in the elevated plus maze, (vi) Striatal and hippocampal neurotransmitter and metabolite levels were also measured. DTM (i) reduced locomotion and rearing frequency, (ii) slightly increased the duration of immobility, (iii) reduced the time engaged in social interaction, (iv) reduced the percentage of entries into and time spent on the open arms of the elevated plus maze, (v) reduced the number of center crossings in the elevated plus maze, (vi) increased striatal serotonin neurotransmitter and its metabolite, and (vii) did not alter motor coordination on the rotarod, grooming duration in the open field test, rectal temperature, or hippocampal neurotransmitter levels. These data suggest that DTM at the present doses and under these experimental conditions presented a similar profile to that of anxiogenic drugs, unrelated with the increased serotonin neurotransmission.

Recent Developments in Neurochemical Imaging in Schizophrenia: An Update

The advent of neurochemical brain imaging methods has provided an opportunity to study the neurochemistry of the human brain in normal and abnormal development. The aim of this article is to provide an update on recent major developments in neurochemical imaging in schizophrenia research. In this concise review, we discuss the major findings on three neurotransmitters, namely dopamine, serotonin and glutamate. The most promising radioligand for D(2)/D(3) neuroreceptor imaging is the agonist [(11)C]PHNO, with higher in vivo affinity for D(3) than D(2) receptors, which can be used to measure amphetamine-induced release of dopamine, and therefore a potential model of dopaminergic alterations in schizophrenia. Recent development of selective radiotracers allow imaging of the serotonin transporter (SERT) using positron emission tomography (PET) with selective tracers such as [(11)C]DASB. Additionally, the glutamatergic hypothesis has evolved from theory to phase III clinical trials of newer agents with novel mechanisms. With the development of newer radioligands and the in vivo application of magnetic resonance spectroscopy (MRS) at relatively high magnetic field strengths, there is ample scope for further neuroimaging advances.

The Endocannabinoid System and its Role in Schizophrenia: A Systematic Review of the Literature

Schizophrenia is a psychiatric disorder whose mechanisms have remained only partially elucidated. The current proposals regarding its biological basis, such as the dopaminergic hypothesis, do not fully explain the diversity of its symptoms, indicating that other processes may be involved. This paper aims to review evidence supporting the involvement of the endocannabinoid system (ECS), a neurotransmitter group that is the target of Cannabis sativa compounds, in this disorder. A systematic review of original papers, published in English, indexed in PubMed up to April, 2012. Most studies employed genetics and histological, neuroimaging or neurochemical methods - either in vivo or post-mortem - to investigate whether components of the ECS are compromised in patients. Overall, the data show changes in cannabinoid receptors in certain brain regions as well as altered levels in endocannabinoid levels in cerebrospinal fluid and/or blood. Although a dysfunction of the ECS has been described, results are not entirely consistent across studies. Further data are warrant to better define a role of this system in schizophrenia.

A Capillary Fraction Collector Coupled to a Fluorescence Reader: A Novel Device to Continuously Quantify Glutamate During Microdialysis

Microdialysis coupled to HPLC is the preferred method for quantification of glutamate (Glu) concentrations, both in normal and pathological conditions. However, HPLC is a time consuming technique that suffers from poor temporal resolution. Here we describe an alternative method to measure glutamate concentrations in small-volume dialysis samples by quantifying hydrogen peroxide released by glutamate oxidase using the Amplex Red method. This system permits continuous automatic sample collection and the detection of a fluorescent reaction product, resorufin, which provides a measure of the glutamate concentration. Quantification can be carried out in small microdialysis samples to allow a temporal resolution of 60 s. Both in vitro and in vivo tests showed that this method was reproducible and reliable, detecting Glu along a linear scale. To validate the proposed method, extracellular Glu concentrations in the rat brain were measured and correlated with electrophysiological activity prior, during and after seizure induction with 4-aminopyridine. This method may be adapted to monitor other biologically active compounds, including acetylcholine and glucose, as well as other compounds that generate hydrogen peroxide as a reaction product and may be used as an alternative to other neurochemical methods.

Mapping prodromal psychosis: A critical review of neuroimaging studies

The onset of schizophrenia is usually preceded by a prodromal phase characterized by functional decline and subtle prodromal symptoms, which include attenuated psychotic phenomena, cognitive deterioration and a decline in socio-occupational function. Preventive interventions during this phase are of great interest because of the impressive clinical benefits. However, available psychopathological criteria employed to define a high risk state for psychosis have low validity and specificity. Consequently there is an urgent need of reliable neurocognitive markers linked to the pathophysiological mechanisms that underlie schizophrenia. Neuroimaging techniques have rapidly developed into a powerful tool in psychiatry as they provide an unprecedented opportunity for the investigation of brain structure and function. This review shows that neuroimaging studies of the prodromal phases of psychosis have the potentials to identify core structural and functional markers of an impending risk to psychosis and to clarify the dynamic changes underlying transition to psychosis and to address significant correlations between brain structure or function and prodromal psychopathology. Additionally, neurochemical methods can address the key role played by neurotransmitters such as dopamine and glutamate during the psychosis onset. To conclude, multimodal neuroimaging may ultimately clarify the neurobiology of the prodromal phases by the integration of functional, structural and neurochemical findings.

Neural mechanism of activity spread in the cat motor cortex and its relation to the intrinsic connectivity

Motor cortical points are linked by intrinsic horizontal connections having a recurrent network topology. However, it is not known whether neural activity can propagate over the area covered by these intrinsic connections and whether there are spatial anisotropies of synaptic strength, as opposed to synaptic density. Moreover, the mechanisms by which activity spreads have yet to be determined. To address these issues, an 8 × 8 microelectrode array was inserted in the forelimb area of the cat motor cortex (MCx). The centre of the array had a laser etched hole ∼500 μm in diameter. A microiontophoretic pipette, with a tip diameter of 2-3 μm, containing bicuculline methiodide (BIC) was inserted in the hole and driven to a depth of 1200-1400 μm from the cortical surface. BIC was ejected for ∼2min from the tip of the micropipette with positive direct current ranging between 20 and 40 nA in different experiments. This produced spontaneous nearly periodic bursts (0.2-1.0 Hz) of multi-unit activity in a radius of about 400 μm from the tip of the micropipette. The bursts of neural activity spread at a velocity of 0.11-0.24 ms⁻¹ (mean=0.14 mm ms⁻¹, SD=0.05)with decreasing amplitude.The area activated was on average 7.22 mm² (SD=0.91 mm²), or ∼92% of the area covered by the recording array. The mode of propagation was determined to occur by progressive recruitment of cortical territory, driven by a central locus of activity of some 400 μm in radius. Thus, activity did not propagate as a wave. Transection of the connections between the thalamus and MCx did not significantly alter the propagation velocity or the size of the recruited area, demonstrating that the bursts spread along the routes of intrinsic cortical connectivity. These experiments demonstrate that neural activity initiated within a small motor cortical locus (≤ 400 μm in radius) can recruit a relatively large neighbourhood in which a variety of muscles acting at several forelimb joints are represented. These results support the hypothesis that the MCx controls the forelimb musculature in an integrated and anticipatory manner based on a recurrent network topology

The spontaneous firing rates of dopamine-inhibited dorsomedial arcuate neurons exhibit a diurnal rhythm in brain slices obtained from ovariectomized plus estrogen-treated rats

The activity of tuberoinfundibular dopaminergic (TIDA) neurons exhibits a diurnal rhythm in female rats, as determined by neurochemical investigation. Whether the spontaneous firing rates of presumed TIDA neurons in the dorsomedial arcuate nucleus (dmARN) also exhibit a diurnal pattern has yet to be ascertained. Single-unit activities of 131 dmARN neurons were recorded in brain slices prepared from 83 ovariectomized plus estrogen-primed rats, and grouped according to their responses to dopamine and the time at which they were observed. In dopamine-inhibited dmARN neurons, significantly lower firing rates were observed in the afternoon compared to those recorded in the morning (2.51 ± 0.27 Hz, n = 15, from 1130 to 1330 h vs. 1.08 ± 0.07 Hz, n = 47, from 1430 to 1630 h). No such change was observed in dopamine-excited or nonresponsive dmARN neurons (1.83 ± 0.32 Hz, n = 9 vs. 1.46 ± 0.17 Hz, n = 21). Four dmARN neurons were continuously recorded from 1130 to 1600 h or even longer until 2000 h. The averaged firing rates decreased significantly between 1300 and 1600 h, two neurons were also inhibited by dopamine and a selective D 2 receptor agonist, PHNO, in both normal and low Ca 2+, high Mg 2+ perfusion mediums. This study revealed the existence of diurnal changes in the firing rates of dopamine-inhibited dmARN neurons. These results are strongly correlated with the rhythmic changes observed in TIDA neuronal activity determined through neurochemical methods.

Respective implications of glutamate decarboxylase antibodies in stiff person syndrome and cerebellar ataxia

BackgroundTo investigate whether Stiff-person syndrome (SPS) and cerebellar ataxia (CA) are associated with distinct GAD65-Ab epitope specificities and neuronal effects.MethodsPurified GAD65-Ab from neurological patients and monoclonal GAD65-Ab with distinct epitope specificities (b78 and b96.11) were administered in vivo to rat cerebellum. Effects of intra-cerebellar administration of GAD65-Ab were determined using neurophysiological and neurochemical methods.ResultsIntra-cerebellar administration of GAD65-Ab from a SPS patient (Ab SPS) impaired the NMDA-mediated turnover of glutamate, but had no effect on NMDA-mediated turnover of glycerol. By contrast, GAD65-Ab from a patient with cerebellar ataxia (Ab CA) markedly decreased the NMDA-mediated turnover of glycerol. Both GAD65-Ab increased the excitability of the spinal cord, as assessed by the F wave/M wave ratios. The administration of BFA, an inhibitor of the recycling of vesicles, followed by high-frequency stimulation of the cerebellum, severely impaired the cerebello-cortical inhibition only when Ab CA was used. Moreover, administration of transcranial direct current stimulation (tDCS) of the motor cortex revealed a strong disinhibition of the motor cortex with Ab CA. Monoclonal antibodies b78 and b96.11 showed distinct effects, with greater effects of b78 in terms of increase of glutamate concentrations, impairment of the adaptation of the motor cortex to repetitive peripheral stimulation, disinhibition of the motor cortex following tDCS, and increase of the F/M ratios. Ab SPS shared antibody characteristics with b78, both in epitope recognition and ability to inhibit enzyme activity, while Ab CA had no effect on GAD65 enzyme activity.ConclusionsThese results suggest that, in vivo, neurological impairments caused by GAD65-Ab could vary according to epitope specificities. These results could explain the different neurological syndromes observed in patients with GAD65-Ab.

Antidepressant-like effect of trans-resveratrol: Involvement of serotonin and noradrenaline system

The antidepressant-like effect of trans-resveratrol, a phenolic compound present in polygonum cuspidatum, was evaluated through behavioral and neurochemical methods. trans-Resveratrol (20, 40 and 80 mg/kg, via gavage) significantly decreased the immobility time in mouse models of despair tests, but did not influence locomotor activity. Two behavioral models and neurochemical assays suggested that trans-resveratrol produced a significant increase in serotonin and noradrenaline levels at 40 or 80 mg/kg in brain regions. In addition, trans-resveratrol dose dependently inhibited MAO-A activity. These findings indicate that the antidepressant-like effect of trans-resveratrol might be related to serotonergic and noradrenergic activation.

Neonatal Diagnosis and Treatment of Menkes Disease

Infants diagnosed with Menkes disease early by plasma neurochemical methods and treated early, within 22 days after birth, with copper replacement therapy, had a 92% survival rate vs 13% in those treated late, Median follow-up in 12 newborns treated early was 4.6 years compared to 1.8 years in 15 diagnosed and treated late.

Effects of anti–glutamic acid decarboxylase antibodies associated with neurological diseases

Glutamic acid decarboxylase (GAD) catalyzes the conversion of glutamic acid into GABA. GAD autoantibodies (GAD-Ab) have been described in diabetes mellitus and in diseases involving the central nervous system such as stiff-person syndrome and cerebellar ataxia. However, the pathogenic role of GAD-Ab in neurological diseases remains a matter of debate. Using neurophysiological and neurochemical methods, we analyzed the effects of intracerebellar and paraspinal administration of GAD-Ab in rats. Intracerebellar administration of IgG from patients with GAD-Ab and neurological involvement (IgG-GAD) blocked the potentiation of the corticomotor response normally associated with trains of repetitive peripheral nerve stimulation. When injected in the lumbar paraspinal region, IgG-GAD induced continuous motor activity with repetitive discharges, abnormal exteroceptive reflexes, and increased excitability of anterior horn neurons, as assessed by F/M ratios. Furthermore, IgG-GAD significantly reduced the N-methyl-D-aspartate-mediated production of nitric oxide in cerebellar nuclei and impaired the synaptic regulation of glutamate after N-methyl-D-aspartate administration. These effects were not observed after administration of IgG from the following groups: (1) patients with GAD-Ab, diabetes mellitus, and without neurological complications; and (2) control patients. These results indicate that stiff-person syndrome and cerebellar ataxia are the direct consequence of antibody-mediated neuronal dysfunction.