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Using two inbred strains of mice which have similar rates of alcohol metabolism, we asked whether prenatal alcohol exposure would cause greater incidence and severity of defects in the development of two forebrain fiber tracts, the corpus callosum and the anterior commissure, in mice prone to these defects (BALB/c) than in mice not prone to these defects (C57BL/6). Pregnant animals were fed 0.6 kcal/g body weight of a Sustacal-based liquid diet containing 0, 15, 17.5, 20, or 25% ethanol-derived calories from day 7 to fetal assessment on day 18 of gestation. Most of alcohol's greatest effects and the greatest strain differences in alcohol's effects on fetal variables were produced by the 17.5% diet. This dose had inhibitory effects on fetal body, brain, and midsagittal corpus callosum and anterior commissure growth. All these effects, except that on brain weight, were significantly greater in C57s than in BALBs. When the results were compared with prenatal growth curves for normal untreated mice, the effect of alcohol on corpus callosum but not anterior commissure growth was largely explained by its effects on overall development. The 17.5% diet had a greater specific effect on size of the anterior commissure in C57s than BALBs but increased the incidence and severity of its permanent dysmorphology in BALBs more than in C57s. Anterior commissure size and morphology may be sensitive indicators of alcohol's effects on prenatal brain development. Hereditary differences in rate of maternal alcohol metabolism no doubt have important consequences for risks arising from prenatal alcohol exposure. However, this study clearly indicates that inherited factors, other than those that influence rate of alcohol metabolism, are important influences on the overall fetal response and the specific responses of the anterior commissure to prenatal alcohol exposure.

Brain-Machine Interfaces (BMIs) have shown great potential for generating prosthetic control signals. Translating BMIs into the clinic requires fully implantable, wireless systems; however, current solutions have high power requirements which limit their usability. Lowering this power consumption typically limits the system to a single neural modality, or signal type, and thus to a relatively small clinical market. Here, we address both of these issues by investigating the use of signal power in a single narrow frequency band as a decoding feature for extracting information from electrocorticographic (ECoG), electromyographic (EMG), and intracortical neural data. We have designed and tested the Multi-modal Implantable Neural Interface (MINI), a wireless recording system which extracts and transmits signal power in a single, configurable frequency band. In prerecorded datasets, we used the MINI to explore low frequency signal features and any resulting tradeoff between power savings and decoding performance losses. When processing intracortical data, the MINI achieved a power consumption 89.7% less than a more typical system designed to extract action potential waveforms. When processing ECoG and EMG data, the MINI achieved similar power reductions of 62.7% and 78.8%. At the same time, using the single signal feature extracted by the MINI, we were able to decode all three modalities with less than a 9% drop in accuracy relative to using high-bandwidth, modality-specific signal features. We believe this system architecture can be used to produce a viable, cost-effective, clinical BMI.

AbstractDevelopmental studies in animals often violate the assumption of statistical independence of observations due to the hierarchical nature of the data (i.e., pups cluster by litter, correlation of individual observations over time). Mixed effect modeling (MEM) provides a robust analytical approach for addressing problems associated with hierarchical data. This article compares the application of MEM to traditional ANOVA models within the context of a developmental study of prenatal ethanol exposure in mice. The results of the MEM analyses supported the ANOVA results in showing that a large proportion of the variability in both behavioral score and brain weight could be explained by ethanol. The MEM also identified that there were significant interactions between ethanol and litter size in relation to behavioral scores and brain weight. In addition, the longitudinal modeling approach using linear MEM allowed us to model for flexible weight gain over time, as well as to provide precise estimates of these effects, which would be difficult in repeated measures ANOVA. © 2007 Wiley Periodicals, Inc. Dev Psychobiol 49: 664–674, 2007.

Preformed gas bubbles can increase energy absorption from an ultrasound beam and therefore they have been proposed for an enhancer of ultrasound treatments. Although tissue temperature measurements performed in vivo using invasive thermocouple probes and MRI thermometry have demonstrated increased tissue temperature, the microscopic temperature distribution has not been investigated so far. In this study the transfer of heat between bubbles and tissue during focused ultrasound was simulated. Microbubble oscillations were simulated within a rat cortical microvascular network reconstructed from in vivo dual-photon microscopy images and the power density of these oscillations was used as an input term in the Pennes bioheat transfer equation. The temperature solution from the bioheat transfer equation was mapped onto vascular data to produce a three-dimensional temperature map. The results showed high temperatures near the bubbles and slow temperature rise in the tissue. Heating was shown to increase with increasing bubble frequency and insonation pressure, and showed a frequency-dependent peak. The goal of this research is to characterize the effect of various parameters on bubble-enhanced therapeutic ultrasound to allow better treatment planning. These results show that the induced temperature elevations have nonuniformities which may have a significant impact on the bio-effects of the exposure.

The accuracy of poly(U) translation was measured in the post-mitochondrial supernatant from whole brain of 7- and 33-month-old Fischer 344 rats. Measurements were made: under in vitro conditions in which translation fidelity was similar to what is known about the accuracy of translation in vivo; and under stresses of varying Mg2+ concentrations (3-12 mM), pH (6.6-8.4), temperature (26-42 degrees C) and in the presence or absence of 2.4% ethanol. No significant difference could be detected between the responses of old and young extracts, the activities of their Phe- and Leu-tRNA synthetases, and their endogenous amounts of Phe-tRNA and Leu-tRNA, despite the fact that the rats studied corresponded in age (by actuarial criteria) to 90-year-old human beings. The accuracy of poly(U) translation was also studied: in liver and hippocampus extracts from 7- and 33-month-old rats; and in brain extracts from 3- and 29-month-old rats. The results were similar to those obtained in brain extracts from 7-month-old rats. Explanations are provided for the inconsistencies which exist in the literature regarding the effect of aging on the accuracy of protein synthesis. It is shown that the inconsistencies are likely to reflect inadequate methodology in three previous studies rather than biological diversity in the control of translation fidelity in aged animals.

The majority of Alzheimer's disease (AD) cases are sporadic with unknown causes. Many dietary factors including excessive alcohol intake have been reported to increase the risk to develop AD. The effect of alcohol on cognitive functions and AD pathogenesis remains elusive. In this study, we investigated the relationship between ethanol exposure and Alzheimer's disease. Cell cultures were treated with ethanol at different dosages for different durations up to 48 h and an AD model mouse was fed with ethanol for 4 weeks. We found that ethanol treatment altered amyloid β precursor protein (APP) processing in cells and transgenic AD model mice. High ethanol exposure increased the levels of APP and beta-site APP cleaving enzyme 1 (BACE1) and significantly promoted amyloid β protein (Aβ) production both in vitro and in vivo. The upregulated APP and BACE1 expressions upon ethanol treatment were at least partially due to the activation of APP and BACE1 transcriptions. Furthermore, ethanol treatment increased the deposition of Aβ and neuritic plaque formation in the brains and exuberated learning and memory impairments in transgenic AD model mice. Taken together, our results demonstrate that excessive ethanol intake facilitates AD pathogenesis.

Ethanol exposure during fetal development can result in behavioral and neurological deficits, including reduced cognitive functions, retarded growth, and craniofacial abnormalities. Adenosine is an endogenous neuromodulator that fine-tunes the release and/or synaptic activities of several neurotransmitters, including glutamate, dopamine, and serotonin. Our aim was to determine whether ethanol exposure during early development affects adenosine receptors, particularly the A1 receptor subtype, in adult rats. Female rats were given water or 15% (vol/vol) ethanol in water prior to mating and throughout gestation and lactation. Sixty-day-old male rat offspring from these dams were randomly selected and assayed for adenosine A1 receptor expression in four brain areas: cortex, cerebellum, hippocampus, and striatum. Our results indicate that ethanol intake by dams decreased body and brain weights of offspring and reduced both A1 receptor mRNA and protein density in cortex and cerebellum. These preliminary findings indicate that ethanol intake by dams during pregnancy and lactation can affect adenosine A1 receptor signalling in the offspring. A pair-fed controlled study is warranted to explore these findings further.

Rats given intraventricular (i.v.t.) injections of 6-hydroxydopa (90 microgran) showed reduced brain part noradrenaline levels but no change in free choice ethanol consumption, while rats given 6-hydroxydopamine (250 microgram) i.v.t. injections showed reduced brain part noradrenaline and dopamine levels and a reduced free choice ethanol intake. Rats given i.v.t. injections of 5,6-dihydroxytryptamine (50 microgram) showed a reduction of serotonin in the hippocampus and an increase in free choice ethanol consumption. Chronic forced ethanol consumption, achieved by placing rats on a Metrecal--ethanol diet, also increased subsequent free choice ethanol intake, but had no permanent effect on brain part monoamine levels. Rats exposed to ethanol prenatally were hyperactive at 5 weeks of age but not at 10 weeks. At 15 weeks, their ethanol preference was not different from that of controls nor did their brain part monoamine levels differ from those of controls at 16 weeks. These results indicate that disrupting the balance between the monoamine neuro-transmitter systems with the neurotoxins alters the free choice ethanol consumption of rats but that prior chronic exposure to ethanol also changes free choice ethanol consumption in the absence of any permanent change in monoamine levels. The long-term behavioral changes seen in rats exposed to ethanol are not due to permanent alterations in the brain levels of noradrenaline, dopamine, or serotonin.