Temporal Linkage Research Articles

Noradrenergic mechanisms for the anticonvulsant effects of desipramine and yohimbine in genetically epilepsy-prone rats: studies with microdialysis

A large body of evidence suggests that the seizure-prone state of genetically epilepsy-prone rats (GEPRs) results, in part, from deficits in central nervous system noradrenergic function. In order to link the synaptic concentration of norepinephrine (NE) to seizure behavior, we evaluated the effects of both desipramine and yohimbine on convulsions and on extracellular NE and serotonin (5-HT) concentrations in the thalamus of severe seixure GEPRs (GEPR-9s). Under anesthesia, guide cannule were stereotaxically placed over thalami. After recovery from surgery, dialysis probes were inserted and the animals were placed individually into a plexiglass chamber where they were allowed to move about freely. Artificial CSF was prefused and samples were collected for analysis on HPLC with electrochemical detection. Either desipramine (10 and 20 mg/kg) or yohimbine (10mg/kg) was administered i.p. after a stable baseline of NE or 5-HT was established. Significant increases in the extracellular NE concentration were seen after injection of both drugs. Temporal linkage exists between the maximum NE increases and the maximum decrease in audiogenic response score (ARS) for these two agents. No significant increases in the extracelular 5-HT concentration occurred after administration of either desipramine or yohimbine at a dose of 10 mg/kg. We conclude that these two drugs are effective anticonvulsants in GERPs atleast partially because they enhance noradrenergic transmission.

Three-dimensional localization of poly(A) RNA and splicing components in the nucleus

The physical distribution of active genes has long been a subject of interest and speculation, however technical limitations have necessitated that it be addressed only by indirect approaches with sometimes contradictory results. However, developments in fluorescence in situ hybridization methodologies allow the position of specific genes and RNAs to be visualized directly within intact cells, thus providing a more direct means to study such questions. To address whether compartmentalization occurs during the production and processing of pre-mRNA in mammalian somatic cells we have recently investigated the distribution of nuclear polyadenylated transcripts which represent approximately 90% of all pre-mRNA. We found that poly(A) RNA forms discrete nuclear “transcript domains” which are specifically positioned with respect to the underlying genome and contain snRNP antigens of the pre-mRNA splicing class. Several lines of evidence indicate a close spatial and temporal linkage between transcription and processing of pol II RNAs (reviewed in 5), therefore, it is possible that poly(A) RNA transcript domains reflect a clustering of active genes at these sites.

Psychosocial stressors: Concepts, causes and effects.

Key advances in life events research included recognition of the need to differentiate events that were independent of disorder; to take the social context of events into account; to assess life events in terms of the long term threat rather than degree of life change; to determine the temporal linkage between life events and onset of psychiatric disorder; to appreciate the importance of long term difficulties as well as acute events; and to examine the role of vulnerability and protective mechanisms in determining individual differences in response to life events. Stress effects in childhood are considered in terms of possible mediating mechanisms; of turning points in life trajectory; of individual differences in response; of difficulties in the concept and measurement of onset of psychiatric disorder; of possible additivity of negative life events; and of the origins of individual differences in exposure to negative life experiences.

Functional relationships between grasp and transport components in a prehension task

Prehension in adults is a highly developed motor skill that affords the study of how components of a movement are coordinated to produce the near endless variety of acts that serve to acquire objects in near body space. This study used three-dimensional movement analysis to describe the kinematic characteristics and coordination of the transport (the reach) and the manipulation (the grasp) components of prehension. Six subjects reached for and grasped 10 different sized wooden disks. Results indicated that the initial phase of the prehension movement could be considered as structured in advance of the movement in that, over the ten disk sizes, time of limb transport was a constant up to peak deceleration. The time after peak deceleration to object contact, however, increased as disk size decreased. This led to the movement trajectories being uniquely shaped for each disk size and as such did not support a proportional duration based model of motor programming. Other findings indicated that maximum grip aperture was reached progressively sooner as disk size was decreased and that maximum grip aperture was highly related to the size of the to-be-grasped disk. In terms of the coordination between the transport and grasp components, support was not found for a temporal linkage between them nor did their coordination appear to be dependent on a motor program. Rather, from an analysis of the spatial variability of the transport and grasp components, evidence was found for supporting the idea that the coordination between these two components was achieved by a sensorimotor process. Through this process, and given the goal of a prehension movement, it was argued that the two components are linked functionally rather than temporally or spatially. These results are discussed in terms of current sensorimotor models of motor control and prehension.

The control of bimanual aiming movements in Parkinson's disease.

The control of unimanual and bimanual aiming movements by Parkinson's disease and control subjects was examined. Despite greater bimanual movement initiation asynchrony and overall bradykinesia, the Parkinson's disease subjects were affected by the experimental manipulations in the same way as controls. Symmetrical and, more especially, asymmetrical bimanual movements required more preparation time and were executed more slowly by both groups than were unimanual movements. Both groups also showed temporal linkage of movements to targets of different extents--movements which have different movement times when performed unimanually, as well as of the faster and slower limbs. A majority in both groups over-compensated for asynchrony in bimanual movement initiation by modulation of movement times, but there was no group difference in this tendency. The results are discussed in terms of underlying motor control processes and with regard to previous evidence for impaired control of simultaneous movements in Parkinson's disease.

Temporal linkage of glycogen and saturated phosphatidylcholine in fetal lung type II cells.

The developmental profiles of glycogen and surfactant-associated saturated phosphatidylcholine were investigated in type II cells isolated from fetal rat lung. Incorporation of radiolabeled glucose into glycogen and type II cell unlabeled glycogen content decreased as a function of gestational age. Conversely, an increase was noted in radioactive choline incorporation into saturated phosphatidylcholine and in the content of unlabeled saturated phosphatidylcholine as a function of gestational age. Type II cells from days 19 and 21 of gestation were also studied by electron microscopy. Temporal relationships similar to those noted biochemically were observed by morphometric analysis. A decrease in glycogen content and an increase in lamellar bodies (the storage organelles for the pulmonary surfactant) were noted as gestation progressed. These studies biochemically and morphologically demonstrate a temporal relationship between glycogen degradation and saturated phosphatidylcholine synthesis in type II cells isolated from fetal rat lung. These findings provide further support for the use of such type II cell preparations for studies of development at the cellular level.

Ultrastructural studies of early morphogenesis and cytodifferentiation in the embryonic mammalian pancreas

Summary Early morphogensis and cytodifferentiation of mouse embryonic pancreas have been investigated. The organ forms as a broad-based diverticulum whose base narrows to form the duct. A crescent of cells, believed to be involved in morphogenesis, is found in each lateral wall of the gut. Changes of the crescents with time and the ultrastructure of cells in them is discussed. A model is presented to explain elevation of the pancreatic diverticulum which depends upon (1) alteration in crescent cell cross-sectional shape and (2) upon some relative movement of cells out of the crescent region. Low levels of endocrine and exocrine cell-specific product can first be detected as this morphogenetic process starts ( Rutter et al. , 1968 ). Rough endoplasmic reticulum, Golgi apparatus, and various vesicles are seen in presumed exocrine cells at these times, but no prozymogen granules have been found. Prospective B-cells can first be identified by increased cytoplasmic electron density; soon thereafter β-granules appear. These correlations of structure are discussed in light of the biochemical information. All told, the data suggest a close temporal linkage between initial specific synthesis and initial organ morphogenesis.