Effect of ACTH1-24 and ACTH4-10 on distribution of 3H-noradrenaline in the brain of adrenalectomized rats.

Painful stimuli led to a decrease of the radioactive catecholamine pool in adrenalectomized rats. Intraventricular administration of both tritiated noradrenaline and ACTH produced a greater decrease of the labelled catecholamine pool than in the control adrenalectomized rats in 12 to 18 hr following injection. Blocking of monoamino-oxidase activity or biosynthesis by systemic administration of Pargyline or alpha-methyl-tyrosine did not prevent the effect of ACTH on brain catecholamines. It is concluded that ACTH exerts a direct influence on the brain catecholaminergic system and that this effect might be involved in ACTH dependent behavioural responses.     

Effects of ACTH(1-24) and ACTH/MSH(4-10) on isolation-induced distress vocalization in domestic chicks

The effects of centrally administered ACTH(1-24) and ACTH(4-10) on isolation-induced distress vocalizations (DVs) were assessed in the presence or absence of social cues (mirrored and plain environments). A dose-response analysis indicated that ACTH(1-24) at doses of 0.5 nM and above increased DVs relative to controls when the animals were tested in mirrored or social environments which reduce baseline levels of calling. This effect, however, was short-lived (approx. 15 min). When tested again 1 hr after injection, the treated animals did not differ from controls. ACTH/MSH(4-10) had no effect on vocalization when the animals were tested immediately after injection, but marginally increased calling when animals were tested an hour later. In addition to vocalization changes, ACTH(1-24) induced squatting when animals were isolated in the test boxes, and yawning, head shaking, wing flapping and preening when animals were reunited after testing. ACTH(1-24)-treated chicks also exhibited longer latencies to close their eyes when they were held in the cupped hands of the experimenter. Taken together, the results suggest that ACTH(1-24) induces a central state of arousal in chicks that resembles fear/anxiety.     

Strain-specific response in mice to the neonatal administration of ACTH(4-10) fragment: behavior, neurochemistry, and brain morphology

Neonatal injection of the ACTH4-10 fragment (5 micrograms daily for five days) caused genotype-dependent changes in concentrations of some monoaminergic neuromediators and their metabolites in hippocampus and brain stem of adult CBA and 101/HY mice. The catecholaminergic neurons increased in number in hypothalamic zona incerta of adult 101/HY mice. Neonatal injection of the peptide caused also genotype-dependent changes in the exploratory behavior of adult animals. Sound sensitivity was reduced in the 101/HY mice, whereas no sensitivity was revealed in both control and experimental groups of the CBA mice. The effects discovered were suggested to be caused by changes in neuronal differentiation.     

Resistance factor in emotional stress in the brain of rats

The authors review the results of extraction from the brain of emotional stress-resistant donor rats of fractions containing "factor" that causes the increased resistance to stress in recipient rats predisposed to stress. Brain homogenates of donor rats were subjected to thermal treatment, gel filtration on Sephadex G-15 and lyophilization. The fractions extracted are low-molecular weight, thermostable, resistant to pronase hydrolysis and significantly (P less than 0.05) increase the resistance of recipient rats to stress.     

Binding of 3H-spiperone in the mouse brain after intraperitoneal injection

In experiments on mice 3H-spiperone binding after intraperitoneal injection was studied. The binding of 3H-spiperone was saturable in the frontal cortex and subcortical structures, whereas in the cerebellum, the amount of radioactivity increased in a linear manner and was referred to as nonspecific binding. The neuroleptics haloperidol, chlorpromazine and sulpiride given 0.5 h before 3H-spiperone displaced 3H-spiperone in the subcortical structures in a dose-related manner. Although the level of the specific 3H-spiperone binding after intraperitoneal injection was lower than after intravenous injection, the intraperitoneal method is simpler, well reproduced and given results comparable with the intravenous method.     

Antiparallel beta-sheets in the crystal structure of the heptapeptide Met-Glu-His-Phe-Arg-Trp-Gly (ACTH 4-10)

The conformation of the molecules in ACTH 4-10 has been determined as part of a study of the conformations of the biologically active N-terminal fragments of the adrenocorticotropic hormone (ACTH). ACTH 4-10 crystallizes in two different superstructures. The substructure considered in the present work, is monoclinic, space group C2, a = 25.75(1) A, b = 27.78(1) A, c = 20.35(1) A, beta = 114.0(1) degrees, Z = 8 molecules ACTH 4-10 plus 22 weight per cent solvent. The crystals contain antiparallel beta-sheets, the orientations of the side groups are not found, because of disorder. The present crystal structure and those of other linear oligopeptides emphasize that antiparallel beta-sheets are energetically favourable. It is very unlikely, however, that the ACTH 4-10 crystals contain the molecules in their biologically active form.     

Hormonal activity of the ACTH(4-10) analog--a prolonged-action stimulant of learning

Possible hormonal activity of ACTH4-7, a long-acting ACTH4-10 analog (ProGly Pro) was studied. Unlike ACTH5-10 the peptide did not reveal steroidogenic and melanocyte-stimulating activity.     

Centrally administered N-terminal fragments of ACTH (1-10, 4-10, 4-9) display convulsant properties in rabbits

Electroencephalographic and behavioral effects of the following ACTH fragments: 1-4, 4-9, 4-11, 1-10, 4-10, 1-13, 1-17 and 1-24 were studied in rabbits. Sequences 4-9, 1-10 and 4-10 displayed some epileptic properties, i.e., they induced epileptic seizures (only electrographic or also behavioral) or increased hippocampal spiking. The 4-9 sequence seemed to be the common sequence responsible for these proconvulsant effects. The possible involvement of the enkephalinergic system is discussed.     

Effect of (L-Phe7) and (D-Phe7) ACTH 4-7 and an ACTH 4-7 analog with prolonged action on acetylcholinesterase activity in the rat brain

ACTH4-7 and its long-acting analog stimulate acetylcholinesterase activity of different areas of the rat brain. Based on the data concerning the effect of an amino acid mixture equivalent to ACTH4-7 and actinomycin D on acetylcholinesterase activity of the white substance of the large hemispheres it is inferred that the oligopeptide-induced increase in the enzyme activity is linked with the induction of the synthesis of new acetylcholinesterase molecules.     

Morpho-chemical characteristics of the brain of rats genetically predisposed to catalepsy

Cell organization of the cerebral cortex and striatum has been studied by+light optics and enzymatic activity of neuromediators catabolism--histochemically. In layers III and V of the sensomotor cortex and in the nucleus caudatus the number of neurons per unit area is increased, and their size is decreased. Volume of cytoplasm and nuclei of neurons in both layers is decreased, the latter--to less extent. The total amount of the perineuronal glia in the nucleus caudatus is also decreased at the expense of astroglia. In the cerebral cortex it is equal, but the ratio between astro-++- and oligodendroglia is changed. Acetylcholinesterase activity in the layers III and V of the sensomotor cortex is lower than in the control, while monoamine oxidase activity is kept at the control level. The genetically determined anomalies++ of growth and development of the cerebral cells is supposed to be considered as a structural base of the cataleptic state.     

Food entrainment modifies the c-Fos expression pattern in brain stem nuclei of rats

When food is restricted to a few hours daily, animals increase their locomotor activity 2-3 h before food access, which has been termed food anticipatory activity. Food entrainment has been linked to the expression of a circadian food-entrained oscillator (FEO) and the anatomic substrate of this oscillator seems to depend on diverse neural systems and peripheral organs. Previously, we have described a differential involvement of hypothalamic nuclei in the food-entrained process. For the food entrainment pathway, the communication between the gastrointestinal system and central nervous system is essential. The visceral synaptic input to the brain stem arrives at the dorsal vagal complex and is transmitted directly from the nucleus of the solitary tract (NST) or via the parabrachial nucleus (PBN) to hypothalamic nuclei and other areas of the forebrain. The present study aims to characterize the response of brain stem structures in food entrainment. The expression of c-Fos immunoreactivity (c-Fos-IR) was used to identify neuronal activation. Present data show an increased c-Fos-IR following meal time in all brain stem nuclei studied. Food-entrained temporal patterns did not persist under fasting conditions, indicating a direct dependence on feeding-elicited signals for this activation. Because NST and PBN exhibited a different and increased response from that expected after a regular meal, we suggest that food entrainment promotes ingestive adaptations that lead to a modified activation in these brain stem nuclei, e.g., stomach distension. Neural information provided by these nuclei to the brain may provide the essential entraining signal for FEO.     

Accumulation and distribution of samarium-153 in rat brain after intraperitoneal injection

It is well known that rare earth elements (REEs) have come into extensive use in a number of fields. As a result, REEs are becoming closely related to human's daily life. However, until now, the distributions of REEs in the brain are not yet very clear. In this study, Sprague-Dawley male rats were intraperitoneally injected with 0.25 mL of ¹⁵³SmCl₃ solution (containing 10 μg Sm). The brain were perfused with saline to minimize the blood influence. The radioactivities of ¹⁵³Sm in the five brain regions (hypothalamus, cerebellum, hippocampus, corpus striatum, and cerebral cortex) were counted. The results suggested that Sm did enter into the brain. Although only about 0.0003% of the given dose was accumulated in the brain, Sm seemed to be remain in the brain for a long time. The highest amounts and lowest concentrations of ¹⁵³Sm were found in the cerebral cortex, and the highest concentrations of ¹⁵³Sm were found in the hypothalamus.     

Effect of ACTH 4-10 on passive avoidance of rats lacking vasopressin (Brattleboro strain).

The hypothesis that the effects of ACTH 4-10 on avoidance are mediated via the release of endogenous vasopressin was investigated. To test this hypothesis, we observed the effect of ACTH 4-10 on the passive avoidance of Brattleboro rats with diabetes insipidus resulting from a total genetic deficiency of vasopressin (DI) and Brattleboro rats without diabetes insipidus (HE). Normal Long-Evans rats (LE) were also included for comparison purposes. The results did not support the hypothesis. ACTH 4-10 did influence the passive avoidance of DI rats; this should not have occurred if the release of endogenous vasopressin is necessary for ACTH 4-10 to influence avoidance.     

Neurochemical effects of the synthetic ACTH4-9-analog Hoe 427 (Ebiratide) in rat brain

The ACTH4-9-analog Hoe 427 systemically injected in a dose range from 0.01-10 micrograms/kg caused a fall in acetylcholine (ACh) content in different brain areas of the rat. This effect occurred 0.5 hour after a single administration and lasted up to 24 hours. The decrease in ACh content induced by Hoe 427 was more pronounced when the animals were pretreated with dexamethasone (over 7 days 1 mg/kg SC, daily). Coadministration of the choline uptake inhibitor hemicholinium-3 (HC-3) and Hoe 427 potentiated the decrease in ACh content induced by HC-3. In the same dose range Hoe 427 acutely evoked an increase of the activity of the enzyme choline acetyltransferase as well as an elevation of brain cyclic GMP content. These data indicate that Hoe 427 enhances ACh metabolism in rat brain after systemic administration.     

运动训练对大鼠主动脉应力和NF-κB及c-fos表达的影响

目的：探讨不同强度运动训练对大鼠主动脉应力和NF-κB及c-fos表达的影响。方法：采用跑台训练方式,建立大鼠有氧运动和疲劳运动模型,运用免疫组织化学SABC法研究不同强度运动训练对大鼠主动脉VEC和VSMC中NF-κB及c-fos表达的影响。结果：胸主动脉血压的变化与对照组比较,有氧训练和疲劳训练均显著性升高（P〈0．05）,但有氧训练与疲劳训练之间差异不显著。与对照组比较,有氧训练大鼠VEC和VSMC中NF-κB和c-fos均显著性下调表达,胸主动脉张开角显著性升高（P〈0．05）,疲劳训练大鼠VEC和VSMC中NF-κB和c-fos均显著性上调表达（P〈0．05）。与有氧运动组比较,疲劳运动大鼠VEC和VSMC中NF-κB和c-fos表达与胸主动脉张开角升高均具有显著性差异（P〈0．05）。表明不同强度运动大鼠主动脉VEC中NF-κB和c-fos表达变化趋势不同,疲劳训练组表达的增加趋势更显著。结论：运动可引起大鼠主动脉VEC和VSMC NF-κB及c-fos表达的变化,且与运动强度关系密切。有氧训练引起的慢性剪切应力变化可使主动脉VEC和VSMC NF-κB加及c-fos显著性下调表达,与VEC和VSMC维持血管功能的稳态有关;疲劳训练可导致壁面摩擦剪切力、周向应力增加,过度的剪切力作用可引起主动脉VEC和VSMC NF-κB及c-fos显著性上调表达,血管张开角显著增加,血管发生非均匀生长,引起血管结构与功能的重塑。