Mitochondria and neuroplasticity

The production of neurons from neural progenitor cells, the growth of axons and dendrites and the formation and reorganization of synapses are examples of neuroplasticity. These processes are regulated by cell-autonomous and intercellular (paracrine and endocrine) programs that mediate responses of neural cells to environmental input. Mitochondria are highly mobile and move within and between subcellular compartments involved in neuroplasticity (synaptic terminals, dendrites, cell body and the axon). By generating energy (ATP and NAD⁺), and regulating subcellular Ca²⁺ and redox homoeostasis, mitochondria may play important roles in controlling fundamental processes in neuroplasticity, including neural differentiation, neurite outgrowth, neurotransmitter release and dendritic remodelling. Particularly intriguing is emerging data suggesting that mitochondria emit molecular signals (e.g. reactive oxygen species, proteins and lipid mediators) that can act locally or travel to distant targets including the nucleus. Disturbances in mitochondrial functions and signalling may play roles in impaired neuroplasticity and neuronal degeneration in Alzheimer''s disease, Parkinson''s disease, psychiatric disorders and stroke.     

Effect of weightlessness and artificial gravitation on thyroid gland morphology]

The investigation of the thyroid gland was carried out in Wistar rats, SPF colony 4.5--13 h and 25 days after a 18.5 days flight on board the space biosatellite "Cosmos-936". In animals subjected to weightlessness, moderate symptoms of the thyroid hypofunction were observed, statistically significant decrease in number and volume of the nuclei in calcitonin-secreting cells (C-cells) was especially pronounced during 4.5--9 h after landing. Similar but less pronounced changes were observed in C-cells of the rats subjected to artificial conditions of space flight, besides weightlessness. The similarity of the changes in the animals of both groups made it possible to connect the increasing amount of C-cells and the morphological symptoms of their functional inhibition with the effect of weightlessness and hypokinesia. During the space flight, the animals were kept under the conditions of artificial gravitation on board the biosatellite and therefore morphological peculiarities specific for the earth conditions were preserved in C-cells and the thyroid gland. Thus, it was concluded that artificial gravitation prevented the development of the thyroid changes which appeared under the influence of weightlessness.     

The development OF THE vestibular apparatus under conditions of weightlessness]

The spawn of the aquarium fish Brachydanio rerio was developing during 5--6 days under conditions of weightlessness (first on board the spaceship "Sojuz-16", then in the space station "Salut-4") in special aquariums "EMKON", in thermostable installations. Electron microscopically the embryos were found to have a well developed labyrinth in early developmental histologically and cytologically differentiated receptory structures of the macula utriculi and macula saccili. In contrast to controls, the experimental animals showed certain alterations in the otolite organization. In similar experiments the embryos of clawed frog Xenopus laevis in the stage of the tail bud were also placed in special containers "EMKON" and thermostable apparatus "Biotherm-4" and by the spaceship "Sojuz-17" were brought to the space station "Salut-4", where it stayed for 16 days. The initial embryos had already had a well developed acoustic vesicle with macula communis. Inspite of the preliminary load by start acceleration and staying under conditions of weightlessness, they reached the general development fairly similar to controls. As it was shown electron microscopically their labyrinth had highly histologically and cytologically differentiated structures. However, a disturbance of the development of the otolithic membrane and otoconia should be noted. The alterations observed in the otolithic membrane organization in experimental fishes and frogs may be explained by general disorders in calcium metabolism.     

Autonomic components of voluntary responses in children of different ages]

The formation of a complex of vegetative-somatic components of constructive activity (assembling figures out of mosaic chips) was analysed in children in the ontogenetic aspect during elaboration of a dynamic stereotype to direct stimuli (with presentation of samples) and during instantaneous formation of voluntary reactions to stimuli of a mainly second signal nature (without presentation of samples). The complex of effector vegetative-somatic components became more complicate and elaborate in the course of the child's growth, beginning with areflexia and disintegration in children of the younger groups (aged from two to three years) and up to correlated synchronous reflex changes of these components in children of the older group (six to seven years old).     

Random root movements in weightlessness

The dynamics of root growth was studied in weightlessness. In the absence of the gravitropic reference direction during weightlessness, root movements could be controlled by spontaneous growth processes, without any corrective growth induced by the gravitropic system. If truly random of nature, the bending behavior should follow socalled 'random walk' mathematics during weightlessness. Predictions from this hypothesis were critically tested.
In a Spacelab ESA-experiment, denoted RANDOM and carried out during the IML-2 Shuttle flight in July 1994, the growth of garden cress ( Lepidium sativum ) roots was followed by time lapse photography at 1-h intervals.
The growth pattern was recorded for about 20 h. Root growth was significantly smaller in weightlessness as compared to gravity (control) conditions.
It was found that the roots performed spontaneous movements in weightlessness. The average direction of deviation of the plants consistently stayed equal to zero, despite these spontaneous movements. The average squared deviation increased linearly with time as predicted theoretically (but only for 8–10 h).
Autocorrelation calculations showed that bendings of the roots, as determined from the 1-h photographs, were uncorrelated after about a 2-h interval.
It is concluded that random processes play an important role in root growth. Predictions from a random walk hypothesis as to the growth dynamics could explain parts of the growth patterns recorded. This test of the hypothesis required microgravity conditions as provided for in a space experiment.     

Theoretical aspects of neuroplasticity.

The authors propose an integrative theory of the organization of neuroplastic processes. Neuroplasticity is assumed to be one of the essential characteristics of the nervous tissue which may be manifested comparatively rapidly and result in reversible changes (functional plasticity). It may also modulate the expression of genotype into phenotype (adaptation) and thus bring about long-lasting effects. Neuroplastic mechanisms are triggered by various natural or artificial stimuli, which may arise in the internal or external environment, and they may differ quantitatively or qualitatively. The effects of plasticity can lead to either positive or negative changes during development (evolutionary plasticity), after short-term exposition (reactive plasticity), after long-term or continuous stimuli (adaptational plasticity), and during functional or structural recovery of damaged neuronal circuits (reparation plasticity). Manifestations of plasticity have probably the same basis, irrespective of the cause which triggered them or the brain region where they were accomplished. Neuroplastic mechanisms are based on the modulation of signal transmission across synapses. They can be related to interneuronal relations. The resulting changes may occur in the communication between neurons (synaptic level), in the activity of local neuronal circuits (at the level of local circuits) or in the relations between individual functional brain systems (multimodular level).     

Gravitropically-stimulated seedlings show autotropism in weightlessness

In a spaceflight experiment, autotropism by oat ( Avena sativa L.) coleoptiles following gravitropic responses was prominent in weightlessness: counter-reactions led to the straightening of the curved coleoptiles. This was not the case during clinorotation on earth. The autotropic reactions appeared to be related to the stimulus received during the stimulus period, i.e. the greater the response the greater the autotropic counter-reaction. Previous models of the gravitropic system which predicted that coleoptiles would not straighten in weightlessness are disproved. A modification to one of the models is proposed which includes the autotropic response observed in spaceflight. The nature of the counter-reactions in the absence of gravitropic stimulation is discussed.     

Cardiopulmonary adaptation to weightlessness

The lung is profoundly affected by gravity. The absence of gravity (microgravity) removes the mechanical stresses acting on the lung paranchyma itself, resulting in a reduction in the deformation of the lung due to its own weight, and consequently altering the distribution of fresh gas ventilation within the lung. There are also changes in the mechanical forces acting on the rib cage and abdomen, which alters the manner in which the lung expands. The other way in which microgravity affects the lung is through the removal of the gravitationally induced hydrostatic gradients in vascular pressures, both within the lung itself, and within the entire body. The abolition of a pressure gradient within the pulmonary circulation would be expected to result in a greater degree of uniformity of blood flow within the lung, while the removal of the hydrostatic gradient within the body should result in an increase in venous return and intra-thoracic blood volume, with attendant changes in cardiac output, stroke volume, and pulmonary diffusing capacity. During the 9 day flight of Spacelab Life Sciences-1 (SLS-1) we collected pulmonary function test data on the crew of the mission. We compared the results obtained in microgravity with those obtained on the ground in both the standing and supine positions, preflight and in the week immediately following the mission. A number of the tests in the package were aimed at studying the anticipated changes in cardiopulmonary function, and we report those in this communication.     

Oscillatory growth movements of roots in weightlessness

The gravitropic curvature of lentil roots ( Lens culinaris L. cv. Verte du Puy), grown in near weightlessness and stimulated on a 1-g centrifuge for 5 to 60 min was followed by time lapse photography. The experiment was carried out in the frame of the IML 1 Mission of Spacelab. Due to the applied acceleration field, the tip of the roots bent and reoriented with respect to the acceleration vector. However, visual inspection of the data could indicate an oscillatory movement superimposed on the gravitropic reorientation.
We applied two signal processing techniques, fast Fourier transform (FFT) and maximum entropy spectral analysis (MESA), to provide quantitative data about the oscillatory movements of the lentil roots under gravity free conditions. In the case with very few data points in the time series the MESA method is superior to the conventional FFT. In the lentil root movements, the Fourier analysis could not extract and resolve the oscillatory signals present in the time series. The MESA approach revealed oscillations with periods around 35 and 50 min for the present lentil roots.
Circumnutations are, therefore, present in roots also in weightlessness.     

Diminished plasma cGMP during weightlessness

We performed an experiment within the project "RLF" (Russian long-term flight) on a cosmonaut onboard the space station MIR. For creating an analogue to orthostatic stress, we used lower body negative pressure (LBNP) as stimulus. Decrease in central and peripheral baroreceptor load by LBNP can be used as a cardiovascular countermeasure in cosmonauts or for inducing endocrine responses. Altered steady-state plasma concentration values of volume sensitive hormones have been observed inflight as well as postflight. Within this project we measured plasma ANP and cGMP as second messenger. Changes in plasma cGMP concentration are generally considered to be a good indicator of those in ANP activity. However, in our experiments depression of cGMP during space flight was more impressive than ANP decline. We are not aware of previous measurements of plasma cGMP under these conditions, and believe to be the first to report complete suppression of plasma cGMP during long-term stay in space.     

Corticotropin releasing factor and neuroplasticity in cocaine addiction

Corticotropin releasing factor (CRF), one of the major effectors of stress, plays a major role in the natural course of drug addiction by accelerating the acquisition of psychostimulant self-administration and increasing incentive motivation for the drug itself and for drug-associated stimuli. Stress-induced CRF is also considered a predictor of relapse and is responsible for feelings of anxiety and distress during cocaine withdrawal. Despite this knowledge, the role of CRF has not been explored in the context of recent research on reward-related learning, built on the hypothesis that neuroplastic changes in the mesocorticolimbic circuitry underlie addiction. The present review explores the effects of stress on the pattern of interaction between CRF, dopamine and glutamate in distinct structures of the mesocorticolimbic circuitry, including the ventral tegmental area (VTA), amygdala, bed nucleus of stria terminalis (BNST) and the prefrontal cortex (PFC), after acute and chronic cocaine consumption as well as in early withdrawal and protracted abstinence. A better knowledge of the neurochemical and cellular mechanisms involved in these interactions would be useful to elucidate the role of CRF in cocaine-induced neuronal plasticity, which could be useful in developing new pharmacological strategies for the treatment of cocaine addiction.