An analysis of astrocytic cell lines with different abilities to promote axon growth

The adult mammalian central nervous system (CNS) lacks the capacity to support axonal regeneration. There is increasing evidence to suggest that astrocytes, the major glial population in the CNS, may possess both axon-growth promoting and axon-growth inhibitory properties and the latter may contribute to the poor regenerative capacity of the CNS. In order to examine the molecular differences between axon-growth permissive and axon-growth inhibitory astrocytes, a panel of astrocyte cell lines exhibiting a range of axon-growth promoting properties was generated and analysed. No clear correlation was found between the axon-growth promoting properties of these astrocyte cell lines with: (i) the expression of known neurite-outgrowth promoting molecules such as laminin, fibronectin andN-cadherin; (ii) the expression of known inhibitory molecules such tenascin and chondroitin sulphate proteoglycan; (iii) plasminogen activator and plasminogen activator inhibitor activity; and (iv) growth cone collapsing activity. EM studies on aggregates formed from astrocyte cell lines, however, revealed the presence of an abundance of extracellular matrix material associated with the more inhibitory astrocyte cell lines. When matrix deposited by astrocyte cell lines was assessed for axon-growth promoting activity, matrix from permissive lines was found to be a good substrate, whereas matrix from the inhibitory astrocyte lines was a poor substrate for neuritic growth. Our findings, taken together, suggest that the functional differences between the permissive and the inhibitory astrocyte cell lines reside largely with the ECM.     

Attentional demands of continuously monitoring orientation using vestibular information.

The aim of this series of experiments was to determine whether attention is normally required for continuously processing vestibular information concerning orientation, or is required only when orientation is disrupted (eg by vestibular dysfunction or by conflicting visual and vestibular orientation cues). In the first two studies, healthy subjects were passively oscillated, and indicated when they perceived they were passing through their starting position. There was only weak evidence for interference between performance on this 'continuous orientation monitoring task' and on concurrent mental tasks. However, a third study showed that when patients with vestibular imbalance carried out the continuous orientation monitoring task their performance on a concurrent mental arithmetic task was substantially impaired. This dual task interference was correlated with inaccuracy in judging orientation on the continuous orientation monitoring task, which in turn correlated with severity of recent vestibular symptomatology (assessed by questionnaire). In a fourth experiment, disorientation was induced in healthy subjects by rotating the visual field about the line of sight. Bidirectional interference was observed between monitoring orientation (assessed by accuracy in setting a rod to the perceived vertical) and performance of an arithmetic task. Dual task interference was correlated with baseline levels of disorientation induced by the visual field, as indicated by inaccuracy in judging the visual vertical. These findings suggest that monitoring orientation makes significant demands upon cortical processing resources when disorientation is induced, whether the disorientation results from deficient sensory functioning or from ambiguous perceptual information.     

The etiology, treatment, and prevention of nonorganic failure-to-thrive in infants

Nonorganic failure-to-thrive is a medical-psychological disorder reflecting lack of growth in an infant without apparent physical causes. Children who fail to thrive as infants are at high risk for developmental delays, personality problems, abuse, and death. This article focuses on environmental failure-to-thrive, describing the behavioral characteristics of the nonthriving infant and the family milieu. Aspects of early environments of NOFT infants are profiled, specific intervention strategies are discussed, and recommendations regarding the promotion of intense, consistent multi-disciplinary intervention strategies are advanced.     

A novel GalR2-specific peptide agonist

The galanin peptide family and its three receptors have with compelling evidence been implicated in several high-order physiological disorders. The co-localization with other neuromodulators and the distinct up-regulation during and after pathological disturbances has drawn attention to this neuropeptide family. In the current study we present data on receptor binding and functional response for a novel galanin receptor type 2 (GalR2) selective chimeric peptide, M1145 [(RG)₂-N-galanin(2-13)-VL-(P)₃-(AL)₂-A-amide]. The M1145 peptide shows more than 90-fold higher affinity for GalR2 over GalR1 and a 76-fold higher affinity over GalR3. Furthermore, the peptide yields an agonistic effect in vitro, seen as an increase in inositol phosphate (IP) accumulation, both in the absence or the presence of galanin. The peptide design with a N-terminal extension of galanin(2-13), prevails new insights in the assembly of novel subtype specific ligands for the galanin receptor family and opens new possibilities to apply the galanin system as a putative drug target.     

Functional imaging studies in cannabis users.

Cannabis remains the most widely used illegal drug in the United States. This update examines the available literature on neuroimaging studies of the brains of cannabis users. The majority of studies examining the acute effects of delta-9-tetrahydrocannabinol (THC) administration used PET methods and concluded that administration of THC leads to increased activation in frontal and paralimbic regions and the cerebellum. These increases in activation are broadly consistent with the behavioral effects of the drug. Although there is only equivocal evidence that chronic cannabis use might result in structural brain changes, blood-oxygenation-level-dependent-fMRI studies in chronic users consistently show alterations, or neuroadaptation, in the activation of brain networks responsible for higher cognitive functions. It is not yet certain whether these changes are reversible with abstinence. Given the high prevalence of cannabis use among adolescents, studies are needed to evaluate whether cannabis use might affect the developing brain. Considerable further work, employing longitudinal designs, is also required to determine whether cannabis use causes permanent functional alterations in the brains of adults.