Modulation of the cholinergic activity of bronchial muscle during inhalation of soman.
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Biomedical subjects
Publications and source records attributed to F Fonnum.
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Thyroid function has been investigated in 24 young military cadets participating in a 5 d ranger training course with heavy physical exercise, calorie deficiency and deprivation of sleep. The cadets were divided into three groups, each differing in the amount of sleep and food consumption. The serum levels of thyroid hormones (T4, FT4, T3, rT3) and TBG showed a biphasic pattern during the course. Initially there was an increased secretion concomitant with an increased deiodination of T4 to T3 and rT3 mainly due to physical exercise. When the activities lasted for several days without sufficient food supply the thyroid secretion decreased simultaneously with an alteration of the peripheral conversion of T4 to rT3 instead of T3. A significant correlation was found between the changes in total and free thyroxine (r = 0.9) and between the increase in rT3 and decrease in T3 (r = 0.6). TSH decreased during the first day of activities and remained low throughout the course. The TSH response to TRH stimulation was greatly reduced during the course due to physical exercise and calorie deficiency. The present investigation demonstrates that the thyroid function is strongly affected by prolonged physical exercise and a negative energy balance, whereas sleep deprivation does not have any significant influence. The results indicate that the alteration observed is not regulated just by the hypothalamo-pituitary-thyroid-axis alone.
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Colchicine injections in the supracommissural septum of the rat caused degeneration of several neurons in the nucleus triangularis septi and the nucleus septofimbrialis. The lesions resulted in significant decreases of choline acetyltransferase in the habenula (-34%) and in the nucleus interpeduncularis (-36%), thus demonstrating the existence of a major cholinergic projection to these nuclei from the supracommissural septum. A large fall in choline acetyltransferase was also noticed in the dorsal hippocampus as a consequence of colchicine damage to the fimbria-fornix fibers crossing the injected area.
Intact preganglionic axons can sprout and form new functional synaptic connexions with neurones in the partially denervated superior cervical ganglion of the guinea-pig (Maehlen & Njå, 1981). In the present work we have examined to what extent the degree of sprouting, as measured by intracellular recording, is paralleled by changes in ultrastructural and neurochemical parameters. The mean number of preganglionic axons innervating each neurone, as estimated by intracellular recording from ganglion cells during stimulation of the individual ventral roots, was reduced from about eleven to about two immediately after the partial denervation. However, 5-7 weeks after the operation, when sprouting was complete, each neurone was innervated on average by about seven axons. The estimated mean amplitude of the synaptic potential elicited by each innervating axon (about 5 mV) was only slightly increased after sprouting. Counts of the number of synaptic profiles per unit area of electron microscopical sections of the ganglion were reduced to about 15% of normal 3-4 days after the operation, and increased to about 60% of normal after sprouting (5-7 weeks). The activity of the enzyme choline acetyltransferase was about 20% of the normal value in ganglia examined 3-4 days after partial denervation. After sprouting (5-7 weeks), this value was increased to about 35% of that in normal ganglia. These results show that intact preganglionic sympathetic axons have a substantial growth potential. However, the increase in the choline acetyltransferase activity was smaller than the increase in electrophysiological and ultrastructural measurements. Therefore, compensatory axonal branching and synapse formation may cause a reduction in the supply of choline acetyltransferase to each presynaptic terminal from the parent soma.
The effects of trimethyltin (TMT) on hippocampal CA1 pyramidal cell activity was studied using an in vitro brain slice preparation. TMT (0.6 micron) reduced the orthodromic population spike and increased the threshold for population spike generation. The excitatory postsynaptic potentials (EPSP) were reduced by TMT (0.6-1.1 micron) in a dose dependent manner. The antidromically driven population spike was attenuated by TMT (0.8 micron). These results indicate that TMT alters hippocampal synaptic transmission by depression of the postsynaptic CA1 neuron. An increased perfusion time decreased the TMT dose which produced a depressive effect.
The transmitter-specific autoradiographic method has been used to retrogradely trace the habenulo-interpeduncular cholinergic projection. [3H]Choline injection in the interpeduncular nucleus resulted in remarkable labeling of the fasciculus retroflexus and in very strong accumulation of silver grains in the medial habenula. Brainstem nuclei sending non-cholinergic projections to the interpeduncular nucleus were not labeled. The present findings strongly support the notion of a cholinergic medial habenula-interpeduncular nucleus projection in agreement with recent immunohistochemical evidence, but in contrast to previous immunocytochemical and pharmacohistochemical results.
The glutamate terminals in rat neostriatum were removed by unilateral frontal decortication. Insulin-induced hypoglycemia was accompanied by different changes in amino acids in rostral neostriatum on the intact and lesion side. Thus the glutamate/aspartate ratio, glutamate concentration and glutamine concentration were significantly more reduced and the aspartate concentration more elevated on the non-operated than on the operated side. The results show a higher turnover of glutamate in the non-operated side indicating a higher turnover of the transmitter pool than of the metabolic pool of glutamate. The combination of brain lesions with drugs inhibiting the metabolism points to a new method to investigate the compartmentation of glutamate in the mammalian brain.
The ablation of medial frontal cortex, but not of other separate cortical regions, was accompanied by a significant decrease in high affinity uptake of D-Asp in neostriatum, olfactory tubercle and pyriform cortex. The results indicate that the medial frontal cortex may be an important region for glutamergic/aspartergic cell bodies.
The forebrain cholinergic and GABAergic projections to the habenula and nucleus interpeduncularis have been investigated by means of surgical and kainic acid lesions. Bilateral transection of the stria medullaris caused a 50% decrease of choline acetyltransferase in both the habenula and nucleus interpeduncularis, and a 65% decrease of glutamate decarboxylase in the habenula. Electrolytic lesions of the posterior septum (nucleus triangularis septi and nucleus septo-fimbrialis) accounted for at least 30-40% decrease of the cholinergic parameter in the habenula and nucleus interpeduncularis. Moreover, the choline acetyltransferase decrease in the habenula appeared restricted to the medial part of the nucleus. Kainic acid injections causing very large neuronal destruction in the nucleus of the diagonal band of Broca, and more than 70% decrease of choline acetyltransferase in the dorsal hippocampus, did not affect the cholinergic parameter in either the medial or lateral habenula or nucleus interpeduncularis. Kainic acid injections in the nucleus entopeduncularis resulted in a 40% decrease of glutamate decarboxylase in the habenula. Kainic acid injections in the nucleus of the diagonal band were accompanied by a 40% decrease of glutamate decarboxylase in the medial subdivision only. The present study points at the nuclei of the posterior septum as the source of a major cholinergic projection to the habenula and nucleus interpeduncularis, and reveals a previously unsuspected GABAergic input from the nucleus of the diagonal band to the medial habenula.
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Evidence continues to accumulate indicating that glutamate and aspartate act as excitatory neurotransmitters in a variety of corticofugal pathways. These two amino acids share a common high-affinity uptake system and the activity of this system is reduced when cell bodies giving rise to glutamergic or aspartergic nerve terminals are destroyed. Selective reduction of glutamate or aspartate concentration in association with decreased high-affinity uptake suggests that a given pathway utilizes the amino acid that is selectively reduced. Since various regions of the cerebral cortex vary both functionally and architectonically, it seemed a reasonable possibility that glutamergic and aspartergic neurons in different areas of the cerebral cortex might project differentially upon different subcortical nuclei. We have therefore removed various cortical regions or the olfactory bulk and determined high-affinity D-aspartate uptake and concentrations of glutamate, aspartate, and several other amino acids in the amygdala and thalamus one week later. The cortical areas which project to thalamus and amygdala are virtually exclusively ipsilateral, so that the contralateral homologous area in the same animal may be used as a control.
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The postnatal development of some neurotransmitter parameters was measured in lateral geniculate body, superior colliculus and visual cortex of the rat. The following parameters were studied: (i) high-affinity uptake of L-glutamate or D-aspartate as markers for glutamergic neurons; (ii) high-affinity uptake of GABA, which reflects both glial and neuronal uptake of GABA; (iii) HA beta-alanine uptake as a marker for accumulation of GABA in glial structures; (iv) activity of glutamic acid decarboxylase which reflects GABAergic neurons; and (v) activity of choline acetyltransferase as a cholinergic marker. Km and Vmax were determined for high-affinity uptake of glutamate and GABA in newborn and adult animals. The possible glial influence on the uptake during development is discussed. In lateral geniculate body and visual cortex the HA glutamate uptake showed increasing activity from birth to adulthood, whereas in superior colliculus, the uptake was higher at birth, reaching a small significant peak after 12 days of age, and was then reduced to adult level. Km showed no such change between neonatal and adult animals. At birth, high-affinity GABA-uptake was similar to the adult level in superior colliculus and lateral geniculate body. In visual cortex, the uptake of GABA was 50% of adults. However, on day 15, the GABA uptake showed 2 to 3-fold higher activity in all regions when compared to adult level. Km for GABA uptake in neonatals and adults differed only in lateral geniculate body. High affinity uptake of beta-alanine was 50-80% lower in adults than in newborn rats. Glutamate decarboxylase activity, however, increased continuously in all 3 regions examined. This was true also for choline acetyltransferase.
High affinity glutamate uptake was reduced in the ipsilateral lateral geniculate body by 75% and in the ipsilateral superior colliculus by 50% one week after ablation of the visual cortex in the adult rat. Six days after neonatal removal of visual cortex, there were no effects on the high affinity glutamate uptake in these regions indicating that there were few functionally corticofugal fibres established at birth. Seventy-five days after unilateral neonatal ablation of visual cortex, the glutamate uptake in both ipsi- and contralateral superior colliculus was reduced 50% compared to unoperated controls. The glutamate uptake in the lateral geniculate body was reduced 55% ipsilateral to and 38% contralateral to the lesion. The neonatal lesion had therefore affected the development of glutamate nerve terminals bilaterally in these target regions. Destruction of the visual cortex on the unoperated side caused in these adults an additional bilateral decrease of the glutamate uptake in the superior colliculus, showing the presence of aberrant glutamatergic fibres crossing from the unoperated visual cortex. In the lateral geniculate body, a similar lesion was accompanied only by a reduction in glutamate uptake on the ipsilateral side. The neonatal ablation of visual cortex also induced small changes in glutamate decarboxylase and GABA uptake in superior colliculus 75 days after the operation.
Twenty-four military cadets went through a 5-day period of heavy physical exercise (35% of max O2 uptake), severe calorie supply deficiency (about 36,000 kJ/24 h), and sleep deprivation (2 h of sleep as a total during 5 days). Some cadets compensated for the caloric deficiency, whereas others partly compensated for the sleep deprivation. Fasting and meal- and glucose-induced changes in the plasma concentration of vasoactive intestinal polypeptide (VIP) were measured on separate days during the course and 8 h after the course was finished (day 6). Fasting plasma concentration of VIP increased two- to five-fold during the course, with the highest increase on day 2. The calorie-compensated subjects showed a smaller increase than those who did not receive any calorie or sleep compensation. Intake of a meal or glucose solution lowered the VIP concentration in plasma within 30-60 min to the concentrations found in the control experiments performed several weeks after the course. The results indicate a role of VIP as 'a polypeptide of substrate need'.
The concentrations of alanine, aspartate, gamma-aminobutyric acid, glutamine, glutamate, and glycine were measured in the pigeon optic nerve and in the individual tectal layers. Characteristic topographical distribution patterns were observed for the different amino acids. After unilateral retinal ablation, the concentration of aspartate and glutamate was decreased in the nerve and contralateral tectum. The reduction was restricted to the superficial part of the tectum, which receives a direct retinal input. The maximal loss was measured in the first two layers, where aspartate was reduced by 51% and glutamate by 75% in comparison with the ipsilateral side 4 weeks after ablation. The results favor a special role for aspartate and glutamate in pigeon retino-tectal afferents.
A single subcutaneous injection of L-cysteine (1.2 mg/g body weight) to rats 4 days after birth was followed by atrophy of the brain which was well developed 27--32 days after the injection. It was apparent that the lesioned animals could be divided into two groups (type 1 and 2) on account of the degree of brain atrophy. In type 1, which was observed in 80% of the animals, the body weight was unchanged, but the total brain weight was reduced by about 20%. The brain structures most affected were cerebral cortex, hippocampus and thalamus, each having a 30--40% reduction in wet weight. The atrophy of the posterior part of cortex was particularly pronounced in this type of lesion. In type 2 lesion, which appeared in 10% of the survivors, the atrophy was much more severe. There was a 50% reduction in wet weight of brain and in body weight. The most prominent finding was the atrophy of the whole cortex and the hippocampus which were reduced by 80 and 60% of wet weights respectively. In this type of lesion significant morphological changes were observed in several brain regions such as caudato-putamen, thalamus, pons, medulla oblongata, spinal cord and cerebellum.