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Autism spectrum disorders are complex neuro-developmental disorders whose neurobiology is proposed to be associated with oxidative stress which is induced by reactive oxygen species. The process of oxidative stress can be a target for therapeutic interventions. In this study, we aimed to review the role of oxidative stress, plasma glutathione (GSH), and related factors as the potential sources of damage to the brain as well as the possible related factors which reduce the oxidative stress. Methylation capacity, sulfates level, and the total glutathione level are decreased in autism. On the other hand, both oxidized glutathione and the ratio of oxidized to reduced glutathione are increased in autism. In addition, the activity of glutathione peroxidase, superoxide dismutase, and catalase, as a part of the antioxidative stress system are decreased. The current literature suggests an imbalance of oxidative and anti-oxidative stress systems in autism. Glutathione is involved in neuro-protection against oxidative stress and neuro-inflammation in autism by improving the anti-oxidative stress system. Decreasing the oxidative stress might be a potential treatment for autism.

Artificial neural networks (ANN) are promising tools in learning complex interplay of factors on a particular outcome. We performed this study to compare the predictive power of ANN and conventional methods in prediction of bone mineral density (BMD) in Iranian post-menopausal women. A database of 10 input variables from 2158 participants was randomly divided into training (1400), validation (150) and test (608) groups. Multivariate linear regression and ANN models were developed and validated on the training, and validation sets and outcomes (femoral neck and lumbar T-scores) were predicted and compared on the test group using different numbers of input variables. Results were evaluated by comparing the mean square of differences between predicted and reference values (non-central chi-square test) and by measuring area under the receiver operating characteristic curve (AUROC) around cut-off value of −2.5 for T-scores. For models with less than 3 input variables in femoral neck and 4 variables in spinal column, performance of regression and ANN models was almost the same. As more variables imported into models, ANN outperformed linear regression models. AUROC varied in 2 to 10 variable models as follows: for ANN in spine, from 0.709 to 0.774; linear models in spine, from 0.709 to 0.744; ANN in femoral neck, from 0.801 to 0.867; linear models in femoral neck, from 0.799 to 0.834. The ANN model performed better than five established patient selection tools in the test group. Superior performance of neural networks than linear models demonstrate their advantage especially in mass screening applications, when even a slight enhancement in performance results in significant decrease in number of misclassifications.

We have recently reported a new protocol for inducing long-term depression through activation of GABAAreceptors in the hippocampal slices. This long-term depression is reversed by bicuculline and potentiated by neurosteroids such as alphaxalone. It was also shown that glutamate receptor activity or extracellular calcium are not involved in the induction of this type of long-term depression. The present study investigated the possible relation between muscimol-induced long-term depression and barbiturates/benzodiazepine-induced amnesia and attempts to determine the possible effect of pregnenolone sulfate on muscimol-induced long-term depression. Extracellular recordings were made in the CA1 pyramidal cell layer of rat hippocampal slices following orthodromic stimulation of Schaffer collateral fibres in stratum radiatum (0.01 Hz). It was observed that pentobarbital, benzodiazepines and pregnanolone at concentrations that did not have any effect themselves on the population spike, potentiate the ability of muscimol to induce long-term depression. In addition to this, the long-term depression was either blocked or reversed by pregnenolone sulfate at concentrations (10 μM) where pregnenolone sulfate did not induce any multiple burst or increase of spike size. The results suggest that the potentiation of this type of long-term depression by benzodiazepines and barbiturates can explain the main adverse effect of these drugs, amnesia and cognitive impairment. Moreover, the prevention or reversal of this type of long-term depression by pregnenolone sulfate, may suggest a clinical application of this agent in the management of amnesia or dementia.

1Unlike long‐term potentiation, long‐term depression (LTD) in the central nervous system remains poorly understood. The present study was undertaken to investigate the role of GABAAreceptors in LTD and synaptic plasticity.2Extracellular recordings were made in the CA1 pyramidal cell layer of rat hippocampal slices following orthodromic stimulation of Schaffer collateral fibres in stratum radiatum (0.01 Hz).3Muscimol induced a time‐ and concentration‐dependent LTD of the amplitude of orthodromic potentials. Increasing the stimulation frequency from 0.01 Hz to 1 Hz for 10 s reversed the LTD induced by muscimol. Muscimol also induced LTD in the absence of electrical stimulation.4Adenosine decreased the spike size in a concentration‐dependent manner, but failed to induce LTD.5Alphaxalone and 5α‐pregnan‐3α‐ol‐20‐one at concentrations that did not have any effect themselves on the population spike (0.5 and 1 μM), potentiated the inhibitory effect of muscimol on the population spike size, including concentrations which were not effective by themselves. Both steroids were able to potentiate the ability of muscimol to induce LTD.6Bicuculline, 5 μM, reversed the LTD induced by muscimol, 10 μM.7The NMDA receptor antagonist (±)‐2‐amino‐5‐phosphonopentanoic acid (2‐AP5), the NMDA/ metabotropic antagonist 2‐AP3 and selective metabotropic antagonist L‐(+)‐2‐amino‐3‐phosphonopro‐pionic acid (L(+)‐AP3) failed to modify the LTD. Similarly, quisqualic acid and (1S, 3R)‐aminocyclopentane dicarboxylic acid (ACPD) a selective agonist at metabotropic receptors did not induce LTD or short‐term depression, whereas kynurenic acid prevented the reversal of the LTD obtained at 1 Hz.8It is concluded that LTD can be induced by the selective activation of GABAAreceptors. The lack of involvement of glutamate receptors in our protocol confirms the unique nature of the LTD described here. The phenomenon of GABA‐induced LTD and its reversal by 1 Hz stimulation may represent a novel type of long‐lasting depression by which inhibitory interneurones can modulate pyramidal cell excitability in a frequency‐dependent manner. Unlike long‐term potentiation, long‐term depression (LTD) in the central nervous system remains poorly understood. The present study was undertaken to investigate the role of GABAAreceptors in LTD and synaptic plasticity. Extracellular recordings were made in the CA1 pyramidal cell layer of rat hippocampal slices following orthodromic stimulation of Schaffer collateral fibres in stratum radiatum (0.01 Hz). Muscimol induced a time‐ and concentration‐dependent LTD of the amplitude of orthodromic potentials. Increasing the stimulation frequency from 0.01 Hz to 1 Hz for 10 s reversed the LTD induced by muscimol. Muscimol also induced LTD in the absence of electrical stimulation. Adenosine decreased the spike size in a concentration‐dependent manner, but failed to induce LTD. Alphaxalone and 5α‐pregnan‐3α‐ol‐20‐one at concentrations that did not have any effect themselves on the population spike (0.5 and 1 μM), potentiated the inhibitory effect of muscimol on the population spike size, including concentrations which were not effective by themselves. Both steroids were able to potentiate the ability of muscimol to induce LTD. Bicuculline, 5 μM, reversed the LTD induced by muscimol, 10 μM. The NMDA receptor antagonist (±)‐2‐amino‐5‐phosphonopentanoic acid (2‐AP5), the NMDA/ metabotropic antagonist 2‐AP3 and selective metabotropic antagonist L‐(+)‐2‐amino‐3‐phosphonopro‐pionic acid (L(+)‐AP3) failed to modify the LTD. Similarly, quisqualic acid and (1S, 3R)‐aminocyclopentane dicarboxylic acid (ACPD) a selective agonist at metabotropic receptors did not induce LTD or short‐term depression, whereas kynurenic acid prevented the reversal of the LTD obtained at 1 Hz. It is concluded that LTD can be induced by the selective activation of GABAAreceptors. The lack of involvement of glutamate receptors in our protocol confirms the unique nature of the LTD described here. The phenomenon of GABA‐induced LTD and its reversal by 1 Hz stimulation may represent a novel type of long‐lasting depression by which inhibitory interneurones can modulate pyramidal cell excitability in a frequency‐dependent manner.

Extracellular recordings were made from the CA1 pyramidal cell layer of hippocampal slices in response to stimulation of Schaffer collateral fibres in stratum radiatum. Alphaxalone and 5α-pregnan-3α-ol-20-one potentiated the inhibitory effect of muscimol on the population spike size at low concentrations (0.5 and 1 μM) that had no significant effect on the spike size by themselves. This profile is in agreement with other reports which have described the effect of these neurosteroids as barbiturate-like. Alphaxalone and 5α-pregnan-3α-ol-20-one also at low concentrations potentiated the inhibitory effect of adenosine alone and in the presence of 1 mM barium which blocked adenosine activated potassium channels. Alphaxalone failed to potentiate the inhibitory effect of adenosine in the presence of 1 μM bicuculline. It is concluded that these neurosteroids enhanced the potentiative interaction between adenosine and muscimol in the presence of barium. The results indicate that adenosine's effects are normally enhanced by virtue of the potentiative interaction occurring with endogenous GABA.

We have recently reported a new protocol for inducing long-term depression through activation of GABAA receptors in the hippocampal slice. This long-term depression is reversed by bicuculline and potentiated by neurosteroids such as alphaxalone and 5α-pregnan-3α-o1-20-one. It was also shown that glutamate receptor activity is not involved in the induction of this type of long-term depression. The present study investigates the role of calcium in the induction of this novel form of long-term depression and attempts to determine the mechanism of reversal of muscimol-induced long-term depression. Extracellular recordings were made in the CA1 pyramidal cell layer of rat hippocampal slices following orthodromic stimulation of Schaffer collateral fibres in stratum radiatum (0.01 Hz). It was observed that the muscimol-induced long-term depression can be obtained in the absence of calcium in the bathing medium. In addition to this, the long-term depression was reversed by N-methyl-d-aspartate, kainic acid, high potassium medium, veratrine and the calcium ionophore A23187 but not high calcium (10 mM) medium. High potassium medium in the absence of calcium reversed the long-term depression induced by muscimol 10 μM.