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1.  Neurobiology of Rehabilitation 
Rehabilitation aims to lessen the physical and cognitive impairments and disabilities of patients with stroke, multiple sclerosis, spinal cord or brain injury, and other neurologic diseases. Conventional approaches beyond compensatory adjustments to disability may be augmented by applying some of the myriad experimental results about mechanisms of intrinsic biological changes after injury and the effects of extrinsic manipulations on spared neuronal assemblies. The organization and inherent adaptability of the anatomical nodes within distributed pathways of the central nervous system offer a flexible substrate for treatment strategies that drive activity-dependent plasticity. Opportunities for a new generation of approaches are manifested by rodent and non-human primate studies that reveal morphologic and physiologic adaptations induced by injury, by learning-associated practice, by the effects of pharmacologic neuromodulators, by the behavioral and molecular bases for enhancing activity-dependent synaptic plasticity, and by cell replacement, gene therapy, and regenerative biologic strategies. Techniques such as functional magnetic resonance imaging and transcranial magnetic stimulation will help determine the most optimal physiologic effects of interventions in patients as the cortical representations for skilled movements and cognitive processes are modified by the combination of conventional and biologic therapies. As clinicians digest the finer details of the neurobiology of rehabilitation, they will translate laboratory data into controlled clinical trials. By determining how much they can influence neural reorganization, clinicians will extend the opportunities for neurorestoration.
PMCID: PMC4164200  PMID: 15838110
neurologic rehabilitation; neuroimaging; plasticity; neural regeneration
2.  Sleep Hygiene and Sleep Quality in Italian and American Adolescents 
This study investigated cross-cultural differences in adolescent sleep hygiene and sleep quality. Participants were 1348 students (655 males; 693 females) aged 12–17 years from public school systems in Rome, Italy (n = 776) and Southern Mississippi (n = 572). Participants completed the Adolescent Sleep-Wake Scale and the Adolescent Sleep Hygiene Scale. Reported sleep hygiene and sleep quality were significantly better for Italian than American adolescents. A moderate linear relationship was observed between sleep hygiene and sleep quality in both samples (Italians: R = .40; Americans: R = .46). Separate hierarchical multiple regression analyses showed that sleep hygiene accounted for significant variance in sleep quality, even after controlling for demographic and health variables (Italians: R2 = .38; Americans: R2 = .44). The results of this study suggest that there are cultural differences in sleep quality and sleep hygiene practices, and that sleep hygiene practices are importantly related to adolescent sleep quality.
PMCID: PMC2981826  PMID: 15251909
adolescence; sleep hygiene; sleep quality
3.  Antagonists of the Neurokinin-1 or Dopamine D1 Receptors Confer Protection from Methamphetamine on Dopamine Terminals of the Mouse Striatum 
Methamphetamine (METH) is a highly addictive compound that induces toxicity of the dopamine (DA) terminals of the neostriatum. Exposure to METH induces long-term deficits in dopamine transporter (DAT) and tyrosine hydroxylase (TH) levels as well as induction of glial fibrillary acidic protein (GFAP) in the caudate putamen (CPu) and the nucleus accumbens (NAc). The primary effect of exposure to METH is elevation of the level of extracellular DA; therefore, we assessed the role of the DA D1 receptor (D1R) and neurokinin-1 receptor (NK-1R) on the expression of toxicity. METH was injected intraperitoneally (10 mg/kg) four times at 2-h intervals (an acute toxic dose), and the mice were sacrificed three days after the treatment. Exposure to METH resulted in marked reduction of DAT sites (reduced to 30 and 21% relative to control in medial and lateral aspects of the CPu) assessed by binding of [125I]RTI-121 by autoradiography or Western blot analysis. Pretreatment with the nonpeptide NK-1R antagonist WIN-51,708 (10 mg/kg) 30 min prior to the first and fourth injections of METH prevented the loss of DAT sites of the CPu. Moreover, pretreatment with WIN-51,708 also prevented the reduction of TH levels induced by METH as well as the induction of GFAP in astrocytes. Pretreatment with the D1R antagonist SCH-23390 (0.25 mg/kg) 30 min before the first and fourth injections of METH conferred partial protection on DAT sites of the CPu. These results demonstrate that receptors postsynaptic to the DA terminals of the CPu are needed in order to express the neurotoxic effects of METH on integral components of the DA terminals of the nigrostriatal projection.
PMCID: PMC2894623  PMID: 15542715
Substance P; neurokinin-1 receptor; dopamine D1 receptor; WIN-51,708; SCH-23390; striatum
4.  The Computational Integrated Myocyte 
The presentation outlines an integrative approach for developing a computational model of cardiomyocytes. A modular approach is proposed, and strategies of linking the modules (intermediary metabolism, electrophysiology, and mechanics) of the model are presented. A strong recommendation is given toward an integrated system approach backed by experimental validation.
PMCID: PMC2864609  PMID: 15201177
integrative systems; modeling; cardiomyocyte
5.  Learned Birdsong and the Neurobiology of Human Language 
Vocal learning, the substrate for human language, is a rare trait found to date in only three distantly related groups of mammals (humans, bats, and cetaceans) and three distantly related groups of birds (parrots, hummingbirds, and songbirds). Brain pathways for vocal learning have been studied in the three bird groups and in humans. Here I present a hypothesis on the relationships and evolution of brain pathways for vocal learning among birds and humans. The three vocal learning bird groups each appear to have seven similar but not identical cerebral vocal nuclei distributed into two vocal pathways, one posterior and one anterior. Humans also appear to have a posterior vocal pathway, which includes projections from the face motor cortex to brainstem vocal lower motor neurons, and an anterior vocal pathway, which includes a strip of premotor cortex, the anterior basal ganglia, and the anterior thalamus. These vocal pathways are not found in vocal non-learning birds or mammals, but are similar to brain pathways used for other types of learning. Thus, I argue that if vocal learning evolved independently among birds and humans, then it did so under strong genetic constraints of a pre-existing basic neural network of the vertebrate brain.
PMCID: PMC2485240  PMID: 15313804
speech; song; warble; Broca’s area; Wernicke’s area; dorsal lateral prefrontal cortex; auditory pathway; epigenetic constraints
6.  Songbirds and the Revised Avian Brain Nomenclature 
It has become increasingly clear that the standard nomenclature for many telencephalic and related brainstem structures of the avian brain is based on flawed once-held assumptions of homology to mammalian brain structures, greatly hindering functional comparisons between avian and mammalian brains. This has become especially problematic for those researchers studying the neurobiology of birdsong, the largest single group within the avian neuroscience community. To deal with the many communication problems this has caused among researchers specializing in different vertebrate classes, the Avian Brain Nomenclature Forum, held at Duke University from July 18–20, 2002, set out to develop a new terminology for the avian telencephalon and some allied brainstem cell groups. In one major step, the erroneous conception that the avian telencephalon consists mainly of a hypertrophied basal ganglia has been purged from the telencephalic terminology, and the actual parts of the basal ganglia and its brainstem afferent cell groups have been given new names to reflect their now-evident homologies. The telencephalic regions that were incorrectly named to reflect presumed homology to mammalian basal ganglia have been renamed as parts of the pallium. The prefixes used for the new names for the pallial subdivisions have retained most established abbreviations, in an effort to maintain continuity with the pre-existing nomenclature. Here we present a brief synopsis of the inaccuracies in the old nomenclature, a summary of the nomenclature changes, and details of changes for specific songbird vocal and auditory nuclei. We believe this new terminology will promote more accurate understanding of the broader neurobiological implications of song control mechanisms and facilitate the productive exchange of information between researchers studying avian and mammalian systems.
PMCID: PMC2481519  PMID: 15313771
archistriatum; paleostriatum; hyperstriatum; paleocortex; archicortex; neocortex; cerebrum; pallium; striatum; pallidum; arcopallium; nidopallium; hyperpallium
7.  Cardiovascular Disease Delay in Centenarian Offspring: Role of Heat Shock Proteins 
Cardiovascular disease is a major cause of morbidity and mortality of older Americans. We have demonstrated recently that centenarian offspring, when compared with age-matched controls, avoid and/or delay cardiovascular disease and cardiovascular risk factors. Given recent evidence suggesting that higher circulating levels of HSP70 predict the future development of cardiovascular disease in established hypertensives and a recent study demonstrating a decrease in HSP60 and HSP70 with advancing age, we hypothesized that HSP70 levels would be lower in centenarian offspring compared with controls. The circulating serum concentration of HSP70 in 20 centenarian offspring and 9 spousal controls was analyzed using a modified HSP70 ELISA method. Centenarian offspring showed approximately 10-fold lower levels of circulating serum HSP70 compared with spousal controls (P < .001). The exact biological significance of the extremely low levels of circulating serum HSP70 observed in centenarian offspring thus far is not clear. However, circulating HSP has been shown to correlate in diseases or disorders in which there is destruction or damage to target tissues or organs, including cardiovascular diseases and numerous autoimmune disorders. We hypothesize that low levels of circulating serum HSP70 may be an indicator of a healthy state and point to longevity of the host; therefore, our results suggest that levels of circulating serum HSP70 may be a marker for longevity.
PMCID: PMC1764488  PMID: 15247074
aging; cardiovascular disease; chaperokine; centenarian; heat shock proteins; longevity
8.  Modeling the Actions of β-Adrenergic Signaling on Excitation–Contraction Coupling Processes 
Activation of the β-adrenergic (β-AR) signaling pathway enhances cardiac function through protein kinase A (PKA)–mediated phosphorylation of target proteins involved in the process of excitation–contraction (EC) coupling. Experimental studies of the effects of β-AR stimulation on EC coupling have yielded complex results, including increased, decreased, or unchanged EC coupling gain. In this study, we extend a previously developed model of the canine ventricular myocyte describing local control of sarcoplasmic reticulum (SR) calcium (Ca2+) release to include the effects of β-AR stimulation. Incorporation of phosphorylation-dependent effects on model membrane currents and Ca2+-cycling proteins yields changes of action potential (AP) and Ca2+ transients in agreement with those measured experimentally in response to the nonspecific β-AR agonist isoproterenol (ISO). The model reproduces experimentally observed alterations in EC coupling gain in response to β-AR agonists and predicts the specific roles of L-type Ca2+ channel (LCC) and SR Ca2+ release channel phosphorylation in altering the amplitude and shape of the EC coupling gain function. The model also indicates that factors that promote mode 2 gating of LCCs, such as β-AR stimulation or activation of the Ca2+/calmodulin-dependent protein kinase II (CaMKII), may increase the probability of occurrence of early after-depolarizations (EADs), due to the random, long-duration opening of LCC gating in mode 2.
PMCID: PMC1201510  PMID: 15201146
calcium channels; beta-adrenergic signaling; phosphorylation; excitation-contraction coupling
9.  Effects of Oxalate on IMCD Cells 
Oxalate, a metabolic end product and a major constituent of the majority of renal stones, has been shown to be toxic to renal epithelial cells of cortical origin. However, it is unknown whether inner medullary collecting duct (IMCD) cells that are physiologically exposed to higher concentrations of oxalate also behave in a similar manner. In the present study, we examined the effects of oxalate on IMCD cells. IMCD cells from the mouse were maintained in DMEM/F12 media supplemented with fetal bovine serum and antibiotics. Exposure of IMCD cells to oxalate produced time- and concentration-dependent changes in the light microscopic appearance of the cells. Long-term exposure to oxalate resulted in alterations in cell viability, with net cell loss after exposure to concentrations of 2 mM or greater. The production of free radicals was directly related to the exposure time and the concentration of oxalate. Crystal formation occurred in less than 1 h and cells in proximity to crystals would lose membrane integrity. Compared with IMCD cells, LLC-PK1 cells as well as HK-2 cells showed significant toxicity starting at lower oxalate concentrations (0.4 mM or greater). These results provide the first direct demonstration of toxic effects of oxalate in IMCD cells, a line of renal epithelial cells of the inner medullary collecting duct, and suggest that the cells lining the collecting duct are relatively resistant to oxalate toxicity.
PMCID: PMC1242119  PMID: 15659791
oxalate; IMCD cells; toxicity; free radicals

Results 1-9 (9)