Restoration of emotional stress reactions in rats following disruption of the limbic structures of the brain by delta-sleep-inducing peptide

This report describes studies of delta-sleep-inducing peptide in the mechanism of compensating emotional behavior following disruption of a number of structures of the limbic complex (the septum and amygdala). Studies were performed in male Wistar rats. Peptide was given i.p. at a dose of 60 nmol/kg. The individual/typological characteristics of the rats' behavior and their resistance to stress was predicted using an open field test. Emotional stress was modeled by immobilizing the animals and applying electric shocks to the skin. Stress was assessed in terms of survival, adrenal hypertrophy, and thymic involution in stress conditions. Bilateral lesioning to brain structures was carried out by anodic polarization. The results obtained showed that the septum and amygdala play a significant role in the mechanisms of resistance to emotional stress. Bilateral disruption of these structures significantly decreased the animals' resistance to emotional stress, producing alterations in behavior in the open field test, increasing the lethality of acute emotional stress, and inducing changes in stress marker organs (the adrenals and thymus) in stress conditions, as compared to controls. Administration of peptide to animals with lesions to the septum or amygdala increased their resistance to emotional stress, as indicated by open field test behavior, survival, and adrenal and thymus weight in stress conditions. Thus, doses of delta-sleep-inducing peptide partially reverse reductions in stress resistance in animals with lesions to structures of the limbic complex. Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 83, No. 11-12, pp. 29–38, November–December, 1997.     

Effects of delta-sleep-inducing peptide in cerebral ischemia in rats

Experimental studies were carried out to investigate the neuroprotective effects of delta-sleep-inducing peptide in animals with cerebral ischemia induced by bilateral compression of both carotid arteries, and to compare the efficacy of this peptide with that of MK-801. These studies led to the conclusion that the peptide had pronounced anti-ischemic effects, which were evident within 24 h and consisted of reductions in the severity of postural abnormalities in rats with bilateral cerebral ischemia, along with a reduction in lethality. Comparison of the efficacies of peptide and MK-801 showed the peptide to have the greater neuroprotective effect. These results are regarded as providing an experimental basis for using the peptide as a therapeutic agent in patients with stroke. Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 83, No. 3, pp. 95–99, March, 1997.     

Structural and functional alterations to rat medial prefrontal cortex following chronic restraint stress and recovery

Chronic stress has been shown in animal models to result in altered dendritic morphology of pyramidal neurons of the medial prefrontal cortex (mPFC). It has been hypothesized that the stress-induced dendritic retractions and spine loss lead to disrupted connectivity that results in stress-induced functional impairment of mPFC. While these alterations were initially viewed as a neurodegenerative event, it has recently been established that stress induced dendritic alterations are reversible if animals are given time to recover from chronic stress. However, whether spine growth accompanies dendritic extension remains to be demonstrated. It is also not known if recovery-phase dendritic extension allows for re-establishment of functional capacity. The goal of this study, therefore, was to characterize the structural and functional effects of chronic stress and recovery on the infralimbic (IL) region of the rat mPFC. We compared neuronal morphology of IL layer V pyramidal neurons from male Sprague-Dawley rats subjected to 21 days of chronic restraint stress (CRS) to those that experienced CRS followed by a 21 day recovery period. Layer V pyramidal cell functional capacity was assessed by intra-IL long-term potentiation (LTP) both in the absence and presence of SKF38393, a dopamine receptor partial agonist and a known PFC LTP modulator. We found that stress-induced IL apical dendritic retraction and spine loss co-occur with receptor-mediated impairments to catecholaminergic facilitation of synaptic plasticity. We also found that while post-stress recovery did not reverse distal dendritic retraction, it did result in over extension of proximal dendritic arbors and spine growth as well as a full reversal of CRS-induced impairments to catecholaminergic-mediated synaptic plasticity. Our results support the hypothesis that disease-related PFC dysfunction is a consequence of network disruption secondary to altered structural and functional plasticity and that circuitry reestablishment may underlie elements of recovery. Accordingly, we believe that pharmacological treatments targeted at preventing dendritic retraction and spine loss or encouraging circuitry re-establishment and stabilization may be advantageous in the prevention and treatment of mood and anxiety disorders.     

Increased resistance to emotional stress produced by the endogeneous peptide prolactin

P. K. Anokhin Research Institute of Normal Physiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR K. V. Sudakov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 110, No. 10, pp. 346–348, October, 1990.     

Nitrogen monoxide in the mechanisms of cardiovascular functional resistance to emotional stress

The paper presents the results of examination of the mechanisms of development of different physiological dysfunctions (diminished cardiac electrical stability, fibrillation threshold fall) under emotional stress. Search was made for their drug correction (nitric oxide precursor L-arginine, the NO synthase blocker Ng-methyl-L-arginine and sodium nitrate). Experiments have indicated that L-arginine and sodium nitrate restore cardiac electrical stability. The normalizing effects of NO donors depended on the stage of cardiac disorders.     

Lipid peroxidation in the brain of rats differing in resistance to emotional stress

It is found for each of the rat brain regions studied (cerebral cortex, subjacent white substance, and brainstem) that both the initial levels of 2-thiobarbituric acid-reactive products and the rates of their increment are highest in rats resistant to emotional stress and lowest in stress-prone rats, and that the rates at which lipid peroxidation products accumulate are highest in the brainstem and lowest in the white substance. A correlation is presumed to exist between individual resistance to cerebral ischemia and the rate of lipid peroxidation in particular brain regions of healthy rats. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, № 10, pp. 384–387, October, 1994     

Effect of β-endorphin and delta sleep-inducing peptide on resistance to emotional stress

Bulletin of Experimental Biology and Medicine -     

Adrenal cortex hormones and the testicles in emotional stress in rats with a genetic predisposition to cataleptic responses

Conclusion Wistar rats subjected to prolonged selection for catatonia (GC rats) show no increases in the androgenic functions of the testicles, and have reductions in the mineralocorticoid function of the adrenals. Laboratories for Physiological Genetics (Director: Corresponding Member of the Russian Academy of Sciences L. N. Ivanova) and Evolutionary Genetics (Director: A. L. Markel', Doctor of Biological Sciences), Institute of Cytology and Genetics, Siberian Division, Russian Academy of Sciences, Novosibirsk. Translated from Problemy éndokrinologii, Vol. 43, No, 1, pp. 38–39, January–February, 1997.     

Biogenic amine content in the brains of rats with different levels of resistance to emotional stress

The levels of biogenic amines and of a number of the products of their metabolism were studied in the hypothalamic nuclei in Wistar and August rats, which have different levels of resistance to emotional stress; levels were also studied in structures functionally and anatomically associated with the hypothalamic nuclei, i.e., the reticular formation of the midbrain, the amygdaloid body, the septum, the locus ceruleus, the dorsal cervical nucleus, and the ventral region of the tegmentum. The genotype was found to determine the level of metabolism of biogenic amines in structures of the central nervous system in conditions of emotional stress. In August rats, the activities of the dopaminergic and serotoninergic systems, which are stress-limiting, decreased to a greater extent during 24-hour immobilization stress. Adrenaline levels in structures of the central nervous system in August rats were higher during stress. Changes in the contents of biogenic amines in the paraventricular and ventromedial nuclei of the hypothalamus in Wistar and August rats could affect the preganglionic neurons of the autonomic nervous system. B. I. Lavrent'ev Laboratory of Neurohistology (Director V. I. Dedov). Laboratory of the Physiology of Emotions and Emotional Stress (Director K. V. Sudakov), P. K. Anokhin Science Research Institute of Normal Physiology, Russian Academy of Medical Sciences, Moscow. Translated from Fiziologicheskii Zhurnal I. M. Sechenova, Vol. 81, No. 5, pp. 14–22, May, 1995.     

Delta sleep-inducing peptide as a factor increasing the content of substance P in the hypothalamus and the resistance of rats to emotional stress

The influence of delta sleep-inducing peptide (DSIP, 60 and 120 nmolelkg, intraperitoneally) on the content of substance P (SP) in the hypothalamus of rats was studied in male rats of the August line. It was demonstrated that the administration of DSIP significantly increases the average content of SP in the hypothalamus, as well as its content in animals resistant to and predisposed to emotional stress. A daily one-time administration of DSIP before placing the rats in conditions of stress increases the content of SP in the hypothalamus which was decreased during emotional stress. The preliminary one-time administration of DSIP to animals subjected to a Stressor influence also increases the SP content in the hypothalamus. It was established that a one-time administration of DSIP in a dose of 60 nmolelkg sharply decreases the classical manifestations of stress such as the hypertrophy of the adrenals and involution of the thymus.Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 41, No. 3, pp. 558–563, May–June, 1991.     

The organization of the human cerebral cortex estimated by intrinsic functional connectivity

Information processing in the cerebral cortex involves interactions among distributed areas. Anatomical connectivity suggests that certain areas form local hierarchical relations such as within the visual system. Other connectivity patterns, particularly among association areas, suggest the presence of large-scale circuits without clear hierarchical relations. In this study the organization of networks in the human cerebrum was explored using resting-state functional connectivity MRI. Data from 1,000 subjects were registered using surface-based alignment. A clustering approach was employed to identify and replicate networks of functionally coupled regions across the cerebral cortex. The results revealed local networks confined to sensory and motor cortices as well as distributed networks of association regions. Within the sensory and motor cortices, functional connectivity followed topographic representations across adjacent areas. In association cortex, the connectivity patterns often showed abrupt transitions between network boundaries. Focused analyses were performed to better understand properties of network connectivity. A canonical sensory-motor pathway involving primary visual area, putative middle temporal area complex (MT+), lateral intraparietal area, and frontal eye field was analyzed to explore how interactions might arise within and between networks. Results showed that adjacent regions of the MT+ complex demonstrate differential connectivity consistent with a hierarchical pathway that spans networks. The functional connectivity of parietal and prefrontal association cortices was next explored. Distinct connectivity profiles of neighboring regions suggest they participate in distributed networks that, while showing evidence for interactions, are embedded within largely parallel, interdigitated circuits. We conclude by discussing the organization of these large-scale cerebral networks in relation to monkey anatomy and their potential evolutionary expansion in humans to support cognition.     

Zonal corticosteroid hormone biosynthesis in the adrenal cortex in rats exposed to emotional stress combined with salt loading

Bulletin of Experimental Biology and Medicine -     

Low-molecular peptides in food as factors altering the resistance of rats to emotional stress

The authors studied the resistance of animals to emotional stress when they were given in the diet, as a source of protein, casein and a protein fraction composed of a mixture of amino acids and low-molecular peptides (18 and 2.7%) obtained by reprocessing Saccharomyces cerevisiae yeasts, biomass. The ECG, rheovasogram, systolic arterial pressure, and respiratory rate were studied in rats given a diet containing 18 and 2.7% low-molecular peptides (controls) and in the same animals after 24-hour immobilization. Addition of low-molecular peptides in the indicated concentration to the diet reduced the resistance of animals to emotional stress.     

The mode of projections of single locus coeruleus neurons to the cerebral cortex in rats

Axonal distributions of single locus coeruleus neurons within the cerebral cortex were examined with antidromic stimulation technique combined with cortical lesions (frontal lobotomy and lobectomy). In urethan-anesthetized rats, stimulating electrodes were implanted in 10 points extending over nearly the entire cerebral cortex, and antidromic responses of single locus coeruleus neurons to stimulation of these stimulus sites were analysed. Fifty percent of locus coeruleus neurons examined were activated antidromically from at least one cortical point in the cerebral cortex. The pattern and extent of axonal distributions of single locus coeruleus neurons in the cortex appeared to vary from cell to cell. From the results obtained in rats with the cortical lesions, it is concluded that in addition to locus coeruleus neurons with intracortical axons running from rostral to caudal, there are the neurons projecting to the occipital cortex without innervating the frontal cortex and those projecting simultaneously to the frontal and occipital cortex with two axonal branches. There was no topographic order between the recording sites within the locus coeruleus and the projection sites in the cortex.     

Gaseous exchange and gastric secretion in dogs as related to various functional states of the cerebral cortex

Summary Experiments performed on dogs demonstrated that the change of the functional condition of the dog's brain cortex alters the gas exchange and the gastric secretion.The gastric secretion to bread, meat and milk increases during the first day of formation of conditioned reflex associations. After the reflexes to the same stimuli are formed, both secretion and gaseous exchange drop to a normal level. The process of internal inhibition formation causes an even greater rise of gastric secretion and gaseous exchange. In neurosis, a considerable decrease of the above autonomic functions was noted.Presented by Active Member of the AMN SSSR P. K. Anokhin     

Cellular proliferation in the cerebral cortex following neural excitation in rats

Cortical spreading depression (SD) is characterized by propagation of neuronal/glial membrane depolarization throughout the unilateral cerebral cortex and has been linked to several neurological disorders, including migraine aura and epilepsy. SD induction resulted in a dramatic increase in BrdU-incorporated cells in the ipsilateral cortical hemisphere that was dependent on the number of elicited SD. Immunohistochemical studies revealed that 53% of the BrdU-labeled cells in the SD-generated cortex were NG2 immunopositive and 25% were OX-42 immunopositive. The remaining 22% of BrdU-incorporated cells showed no immunoreactivity to GST-rr, GFAP, NeuN, NG2 or OX-42.These data indicate that functional excitation of the cerebral cortex induces proliferative response in cortical cells, which may subsequently differentiate into glial progenitor or microglia within 3 days after stimulation.