Abstract: The purpose of the present study was to examine the combined effects of aging and lifelong ethanol exposure on the levels of monoamine neurotransmitters in different regions of the brain. This work is part of a project addressing interactions of aging and lifelong ethanol consumption in alcohol-preferring AA (Alko Alcohol) line of rats, selected for high voluntary consumption of ethanol. Intake of ethanol on the level of 4.5–5 g/kg/day for about 20 months induced only limited changes in the neurotransmitter levels; the concentration of noradrenaline was significantly reduced in the frontal cortex. There was also a trend towards lower levels of dopamine and 5-hydroxytryptamine (5-HT) in the frontal cortex, and towards a lower noradrenaline level in the dorsal cortex. Aging was associated with a decreased concentration of dopamine in the dorsal cortex and with a declining trend in the striatum. The levels of 5-HT in the limbic forebrain were higher in the aged than in the young animals, and in the striatum, there was a trend towards higher levels in older animals. The data suggest that a continuous intake of moderate amounts of ethanol does not enhance the age-related alterations in brain monoamine neurotransmission, while the decline in the brain level of dopamine associated with aging may be a factor contributing to age-related neurological disorders.
Abstract: Purpose: To compare neurovascular coupling in the posterior cerebral artery (PCA) between those with spinal cord injury (SCI) and able bodied (AB) individuals. Methods: A total of seven SCI and seven AB were matched for age and sex. Measures included PCA velocity (PCAv), beat-by-beat blood pressure and end-tidal carbon dioxide. Posterior cerebral cortex activation was achieved by 10 cycles of (1) 30 s eyes closed (pre-stimulation), (2) 30 s reading (stimulation). Results: Blood pressure was significantly reduced in those with SCI (SBP: 100 ± 13 mmHg; DBP: 58 ± 13 mmHg) vs. AB (SBP: 121 ± 12 mmHg; DBP: 74 ± 9 mmHg) during both pre-stimulation and stimulation, but the relative increase was similar during the stimulation period. Changes in PCAv during stimulation were mitigated in the SCI group (6% ± 6%) vs. AB (29% ± 12%, P < 0.001). Heart rate and end-tidal carbon dioxide responded similarly between groups. Conclusions: Clearly, NVC is impaired in those with SCI. This study may provide a link between poor perfusion of the posterior cerebral region (containing the medullary autonomic centres) and autonomic dysfunction after SCI.
Abstract: Learning foreign speech contrasts involves creating new representations of sound categories in memory. This formation of new memory representations is likely to involve changes in neural networks as reflected by oscillatory brain activity. To explore this, we conducted time-frequency analyses of electro-encephalography (EEG) data recorded in a passive auditory oddball paradigm using Thai language tones. We compared native speakers of English (a non-tone language) and native speakers of Mandarin Chinese (a tone language), before and after a two-day laboratory training. Native English speakers showed a larger gamma-band power and stronger alpha-band synchrony across EEG channels than the native Chinese speakers, especially after training. This is compatible with the view that forming new speech categories on the basis of unfamiliar perceptual dimensions involves stronger gamma activity and more coherent activity in alpha-band networks than forming new categories on the basis of familiar dimensions.
Abstract: Chronic and excessive alcohol misuse results in changes in the expression of selected miRNAs and their mRNA targets in specific regions of the human brain. These expression changes likely underlie the cellular adaptations to long term alcohol misuse. In order to delineate the mechanism by which these expression changes occur, we have measured the expression of six miRNAs including miR-7, miR-153, miR-152, miR-15B, miR-203 and miR-144 in HEK293T, SH SY5Y and 1321 N1 cells following exposure to ethanol. These miRNAs are predicted to target key genes involved in the pathophysiology of alcoholism. Chronic and chronic-intermittent exposure to ethanol, and its removal, resulted in specific changes in miRNA expression in each cell line suggesting that different expression patterns can be elicited with different exposure paradigms and that the mechanism of ethanol’s effects is dependent on cell type. Specifically, chronic exposure to ethanol for five days followed by a five day withdrawal period resulted in up-regulation of several miRNAs in each of these cell lines similar to expression changes identified in post mortem human brain. Thus, this model can be used to elucidate the role of miRNAs in regulating gene expression changes that occur in response to ethanol exposure.
Abstract: Several cross-sectional functional Magnetic Resonance Imaging (fMRI) studies reported a negative correlation between auditory verbal hallucination (AVH) severity and amplitude of the activations during language tasks. The present study assessed the time course of this correlation and its possible structural underpinnings by combining structural, functional MRI and repetitive Transcranial Magnetic Stimulation (rTMS). Methods: Nine schizophrenia patients with AVH (evaluated with the Auditory Hallucination Rating scale; AHRS) and nine healthy participants underwent two sessions of an fMRI speech listening paradigm. Meanwhile, patients received high frequency (20 Hz) rTMS. Results: Before rTMS, activations were negatively correlated with AHRS in a left posterior superior temporal sulcus (pSTS) cluster, considered henceforward as a functional region of interest (fROI). After rTMS, activations in this fROI no longer correlated with AHRS. This decoupling was explained by a significant decrease of AHRS scores after rTMS that contrasted with a relative stability of cerebral activations. A voxel-based-morphometry analysis evidenced a cluster of the left pSTS where grey matter volume negatively correlated with AHRS before rTMS and positively correlated with activations in the fROI at both sessions. Conclusion: rTMS decreases the severity of AVH leading to modify the functional correlate of AVH underlain by grey matter abnormalities.
Abstract: Fetal Alcohol Spectrum Disorder (FASD) is a general diagnosis for those exhibiting long-lasting neurobehavioral and cognitive deficiencies as a result of fetal alcohol exposure. It is among the most common causes of mental deficits today. Those impacted are left to rely on advances in our understanding of the nature of early alcohol-induced disorders toward human therapies. Research findings over the last decade have developed a model where ethanol-induced neurodegeneration impacts early neural circuit development, thereby perpetuating subsequent integration and plasticity in vulnerable brain regions. Here we review our current knowledge of FASD neuropathology based on discoveries of long-lasting neurophysiological effects of acute developmental ethanol exposure in animal models. We discuss the important balance between synaptic excitation and inhibition in normal neural network function, and relate the significance of that balance to human FASD as well as related disease states. Finally, we postulate that excitation/inhibition imbalance caused by early ethanol-induced neurodegeneration results in perturbed local and regional network signaling and therefore neurobehavioral pathology.