Neuroscience
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Fragile X mental retardation protein (FMRP) binds select mRNAs, functions in intracellular transport of these mRNAs and represses their translation. FMRP is highly expressed in neurons and lack of FMRP has been shown to result in dendritic dysmorphology and altered synaptic function. FMRP is known to interact with mRNAs for the Kv3.1b potassium channel which is required for neurons to fire action potentials at high rates with remarkable temporal precision. ⋯ To examine this hypothesis, we have studied normal human brainstem tissue with immunohistochemical techniques and confocal microscopy. Our results demonstrate that FMRP is widely expressed in cell bodies and dendritic arbors of neurons in the human cochlear nucleus and superior olivary complex and also that coincidence detector neurons of the medial superior olive colocalization of FMRP and Kv3.1b. We interpret these observations to suggest that the lower auditory brainstem is a potential site of dysfunction in FXS.
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Frontal areas are thought to be the coordinators of working memory processes by controlling other brain areas reflected by oscillatory activities like frontal-midline theta (4-7 Hz). With aging substantial changes can be observed in the frontal brain areas, presumably leading to age-associated changes in cortical correlates of cognitive functioning. The present study aimed to test whether altered frontal-midline theta dynamics during working memory maintenance may underlie the capacity deficits observed in older adults. 33-channel EEG was recorded in young (18-26 years, N=20) and old (60-71 years, N=16) adults during the retention period of a visual delayed match-to-sample task, in which they had to maintain arrays of 3 or 5 colored squares. ⋯ Old participants showed reduced frontal theta activity during both tasks compared to the young group. In the young memory maintenance-related frontal-midline theta activity was shown to be sensitive both to the increased memory demands and to efficient subsequent memory performance, whereas the old adults showed no such task-related difference in the frontal theta activity. The decrease of frontal-midline theta activity in the old group indicates that cerebral aging may alter the cortical circuitries of theta dynamics, thereby leading to age-associated decline of working memory maintenance function.
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We previously demonstrated that mice which overexpress human renin and angiotensinogen (R+A+) show enhanced cerebral damage in both in vivo and in vitro experimental ischemia models. Angiotensin-converting enzyme 2 (ACE2) counteracts the effects of angiotensin (Ang-II) by transforming it into Ang-(1-7), thus reducing the ligand for the AT1 receptor and increasing stimulation of the Mas receptor. Triple transgenic mice, SARA, which specifically overexpress ACE2 in neurons of R+A+ mice were used to study the role of ACE2 in ischemic stroke using oxygen and glucose deprivation (OGD) of brain slices as an in vitro model. ⋯ Finally, western blots revealed less Nox2 and Nox4 expression in SARA mice compared with R+A+ mice both before and after OGD. We suggest that reduced brain swelling and cell death observed in SARA animals exposed to OGD result from diminished ROS production coupled with lower expression of Nox isoforms. Thus, the ACE2/Ang-(1-7)/Mas receptor pathway plays a protective role in brain ischemic damage by counteracting the detrimental effects of Ang-II-induced ROS production.
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We examined changes in the variability, frequency composition, and complexity of force signal from subacute to chronic stage of stroke during maintenance of isometric knee extension and compared these parameters between chronic stroke and healthy subjects. The sample included 15 healthy (65±8 years) and 23 chronic stroke subjects (65±14 years, 6-112 months post-stroke) of whom 10 (64±15 years) were also examined 11-22 days post-stroke (subacute stage). The subjects performed isometric knee extension at 10%, 20%, 30%, and 50% of peak torque for 10s (two trials each). ⋯ These results indicate a shift toward lower frequencies and a less complex physiological process underlying force control in chronic stroke. The overall results suggest the improvement in force variability from subacute to chronic stroke but without normalization in the frequency composition and complexity of the force signal. Thus, disordered structure of the force signal remains a marker of impaired motor control long after stroke occurrence despite apparent recovery in force variability.
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The coppery titi monkey (Callicebus cupreus) is a socially monogamous New World primate that has been studied in the field and the laboratory to investigate the behavioral neuroendocrinology of primate pair bonding and parental care. Arginine vasopressin has been shown to influence male titi monkey pair-bonding behavior, and studies are currently underway to examine the effects of oxytocin on titi monkey behavior and physiology. Here, we use receptor autoradiography to identify the distribution of arginine vasopressin 1a receptor (AVPR1a) and oxytocin receptors (OXTR) in hemispheres of titi monkey brain (n=5). ⋯ AVPR1a binding is present throughout the cortex, especially in cingulate, insular, and occipital cortices, as well as in the caudate, putamen, nucleus accumbens, central amygdala, endopiriform nucleus, hippocampus (CA4 field), globus pallidus, lateral geniculate nucleus, infundibulum, habenula, PAG, substantia nigra, olivary nucleus, hypoglossal nucleus, and cerebellum. Furthermore, we show that, in the titi monkey brain, the OXTR antagonist ALS-II-69 is highly selective for OXTR and that the AVPR1a antagonist SR49059 is highly selective for AVPR1a. Based on these results and the fact that both ALS-II-69 and SR49059 are non-peptide, small-molecule antagonists that should be capable of crossing the blood-brain barrier, these two compounds emerge as excellent candidates for the pharmacological manipulation of OXTR and AVPR1a in future behavioral experiments in titi monkeys and other primate species.