跨颅电刺激对大鼠抑郁症的治疗作用

目的：探讨跨颅电刺激对大鼠抑郁症的治疗作用。方法：跨颅电刺激抑郁症大鼠左侧前额叶皮层,敞箱实验测定大鼠行为学变化,荧光法测定单胺类递质含量的变化。结果：跨颅直流电和低频脉冲电刺激后,大鼠敞箱实验中垂直和水平运动得分均较模型组显著升高（P〈0.05）;且大鼠左侧前额叶皮层和海马5-HT、NE含量较模型组显著升高（P〈0.05）,而前额叶皮层DA含量无显著变化（P〉0.05）。结论：直流电和低频脉冲电跨颅刺激左侧前额叶皮层,对抑郁症均有显著治疗作用。     

去垂体幼鼠的生物学特性与激素水平

目的观察去垂体幼鼠的生物学特性的改变,了解去垂体术后幼鼠体内激素水平。方法 80只4周龄SD幼鼠2 d内经咽旁入路行垂体去除术,术后与20只同批系的正常幼鼠置于相同条件下观察并饲养,隔日记录体重、饮水量、进食量、体长、尾长等,1周时测量体温后,放入代谢笼饲养1d,记录尿量,2周时测量体温并经目眦静脉采血,分离冻存,分批测量生长激素(GH)、类胰岛素生长因子-1(IGF-1)、甲状腺激素(FSH、FT3、FT4)、促肾上腺皮质激素(ACTH)等。结果去垂体术后2周中,生物特性明显改变,体重、身长、尾长增长,与正常大鼠比较,去垂体幼鼠存在生长障碍,体温逐渐下降,进食量减低,饮水量、排尿量增加。血清GH、IGF-1、ACTH、FSH、FT3、FT4降低,与对照组相比差异有显著性(P<0.01)。结论去垂体幼鼠生物特性改变,垂体激素水平显著降低。     

Subhypothalamic grafts of human pituitary adenomas in total-body irradiated rats

Summary Human pituitary adenomas proliferate neither in cell culture nor in athymic nude mice. We propose that one or several of the humoral factors necessary for the growth of pituitary adenomas is missing in these experimental environments. The purpose of our experiments was to examine the possible influence of the hypothalamus in supporting cellular proliferation, and thus adenoma growth. Fragments from four human pituitary adenomas (three pituitary prolactinomas; one ACTH-secreting adenoma) were transplanted into the pituitary fossa of total-body irradiated, hypophysectomized rats. The rats were killed after two weeks and perfused with a mixture of formalin and India ink. Histologic examination of serial sagittal sections through the pituitary fossa and the adjacent brain showed: vascularization of the grafts from the pituitary stalk and from the scar tissue in the sphenoid bone; survival of some adenomas; and numerous mitoses in an ACTH-secreting specimen obtained from a patient who had Cushing's disease. We conclude from these experiments that as yet unidentified hypothalamic factors are essential for the growth of certain types of pituitary adenomas.This study was supported by a grant to Dr. Landolt from the Jubiläumsspende of the University of Zürich, Switzerland.The results were presented in part at the Second European Workshop on Pituitary Adenomas, Paris, September 20–22, 1979     

Modifications of plastic properties and metaplasticity of glutamatergic synapses in the rat cortex and hippocampus under conditions of reserpine-induced behavioral depression

Intraperitoneal injection of 1 mg/kg reserpine into rats caused the development of behavioral depression that was especially clearly pronounced 24 h after injection. Under such conditions, induction of long-term potentiation of synaptic transmission was suppressed, the development of long-term depression in glutamatergic synapses of pyramidal neurons of the hippocampal CA1 area and layers II/III of the parietal cortex was facilitated, and metaplasticity threshold (θ_M) was shifted to the right. Such modifications of plasticity and metaplasticity of glutamatergic synapses were determined by changes in the functional state of postsynaptic NMDA receptors, which was confirmed by a decrease in the duration of NMDA component of field EPSPs generated in the studied neurons and by an increase in the sensitivity of this component to the action of a nonselective blocker of NMDA receptors, ketamine. Simultaneously, the sensitivity to zinc and haloperidol, which are selective with respect to NMDA receptors with the subunit composition NR1/NR2B, decreased. It is hypothesized that, under conditions of depression, either replacement of a part of NR2B subunits in the structure of NMDA receptors by NR2A subunits or biochemical inactivation of NMDA receptors containing NR2B subunit, as well as a decrease in the clearance of transmitter in glutamatergic synapses, occur; these events determine the impairment of plastic properties of the latter contacts. Neirofiziologiya/Neurophysiology, Vol. 39, No. 3, pp. 214–221, May–June, 2007.     

Interaction between noradrenergic and glucocorticoid brain systems: Probable involvement in the development of depression

Electrophysiological and biochemical experiments on slices of the rat dorsal hippocampus demonstrated that dexamethasone (100 nM) augmented and prolonged the depressive effect of noradrenaline on synaptic transmission in the CA1 zone; this effect is related to weakening of the uptake of noradrenaline by neurons. The effect of dexamethasone is mediated by glucocorticoid receptors. Inhibitors of presynaptic translocase of noradrenaline, cocaine and imipramine, increased, similarly to dexamethasone, the effects of noradrenaline; an additive synergism was observed upon combined applications of dexamethasone and cocaine. The effect of dexamethasone decreased with an increase in the extracellular concentration of glucose, but increased upon application of the Na/K-ATPase inhibitor strophantin. The potentiating influence of dexamethasone on the effects of noradrenaline was weaker in slices obtained from rats with behavioral depression induced by social isolation or chronic introduction of dexamethasone. We hypothesize that glucocorticoids stabilize noradrenergic neurotransmission in the brain under the action of stressogenic influences. The role of glucocorticoid mechanisms in the development of depression is discussed.Neirofiziologiya/Neurophysiology, Vol. 36, Nos. 5/6, pp. 377–385, September–December, 2004.This revised version was published online in April 2005 with a corrected cover date and copyright year.     

Research advances in geriatric depression

Technical advances have facilitated the exploration of factors related to geriatric depression and have helped generate novel biological and psychosocial treatment approaches. This review summarizes the main advancements in epidemiology, clinical presentation and course, genetics, and other areas of biological research. Treatment interventions outlined in this paper include electroconvulsive therapy, repetitive transcranial magnetic stimulation, magnetic seizure therapy, vagus nerve stimulation, deep brain stimulatn, depression prophylaxis, multidisciplinary approaches to depression treatment, and psychotherapy. Forms of psychotherapy for geriatric depression summarized include interpersonal psychotherapy, supportive psychotherapy, cognitive-behavioral therapy, problem-solving therapy, and ecosystem-focused therapy. Neuroimaging techniques based on magnetic resonance imaging are discussed briefly, including volumetric brain studies, diffusion tensor imaging, fractional anisotropy, fiber tractography, magnetization transfer imaging, and blood-oxygenation-level-dependent functional magnetic resonance imaging. Finally, treatment effectiveness is addressed in a discussion of new models to improve access to and quality of care offered in the community.     

CRF-evoked bradycardia in urethane-anesthetized rats is blocked by naloxone

CRF, injected IV at a dose of 6 nmol/kg, produced a fall in blood pressure and in heart rate in urethane-anesthetized rats. The CRF-bradycardia was not obtained in hypophysectomized animals, in animals pretreated with dexamethasone, or in animals pretreated with the narcotic antagonist, naloxone (1 mg/kg, IV). By contrast, the hypotensive effects of CRF were not affected by these procedures. Vagotomy or pretreatment with a low dose of N-methylnaloxone did not affect the CRF-bradycardia, indicating that the slowing of the heart was not due to parasympathetic stimulation or due to a peripherally mediated opioid chemoreflex. The results suggested that the CRF-bradycardia was mediated by the release of opioid peptides from the pituitary.     

Effect of cycloheximide on the fine structure of corpus luteum in intact and hypophysectomized rats

Summary In rats, one large intravenous dose of cycloheximide leads to extensive development of two types of membrane-formations in the cells of corpora lutea, within two hours. Both the laminated dense bodies (concentric layers of smooth membranes showing high electron density) and the tubular aggregates (tightly packed smooth tubules with diameter smaller than usual) exhibited obvious connections with endoplasmic reticulum membranes. The reorganization of tubular aggregates gave rise to crystalloids showing hexagonal symmetry. The crystalloids, being obviously unstable, were transformed into smooth fingerprints (concentric arrays of paired agranular membranes showing the same density as endoplasmic reticulum membranes). Hypophysectomy, performed 24 hours previously, moderated but did not totally abolish the development of membranous configurations. The described effect of cycloheximide is considered to represent cellular injury, probably due to membrane-denaturation.This work was supported in part by the Medical Research Council of Canada (Block Term Grant MT-1829), the Ministère des Affaires Sociales, Quebec, and Succession J.A. DeSève. The authors thank the Upjohn Company, Kalamazoo, Michigan, U.S.A., for the cycloheximide used in these experiments.Fellow of the Medical Research Council of Canada.     

Cell kinetics of the growth plate in hypophysectomized rats treated with growth hormone and thyroxine

Summary The cell production in the growth plate of the proximal tibia was calculated in hypophysectomized rats given growth hormone and/or thyroxine from values of longitudinal bone growth determined with oxytetracycline and the size of degenerative cells in the growth plate.The changes in longitudinal bone growth induced by thyroxine and growth hormone in hypophysectomized rats were found to be predominantly caused by changes in the cell production, whereas the changes in the size of the degenerative cells were minor. The stimulation of cell production by growth hormone was dependent on the dose and the administration period. Thyroxine was found to stimulate the cell production up to an optimum dose of thyroxine.     

Evidence that behavioral depression does not influence airway cell influx in allergic rats

This study was designated to evaluate the influence of behavioral depression on the airway leukocyte recruitment in allergic animals. To achieve this, total and differential cell counts in bronchoalveolar (BAL) fluid of ovalbumin (OVA)-sensitized and depressed rats was evaluated. Inescapable electric footshock, applied on day 0, 7 and 13 after OVA sensitization, was used as a model to induce depression. In both nondepressed and depressed groups, the number of total and differential cells (eosinophils and mononuclear cells) in BAL fluid was significantly larger in sensitized compared with non-sensitized animals. However, no statistical differences were found between these groups with respect to the number of total and differential leukocytes, irrespective of the day inescapable shock was applied. Thus, behavioral depression does not influence the pattern of cell infiltration into the airways of allergen-induced airway inflammation.     

Effects of corticotropin releasing factor on locomotor activity in hypophysectomized rats

Corticotropin releasing factor (CRF) injected intracerebroventricularly to hypophysectomized and sham hypophysectomized rats produced a dose dependent increase in locomotor activity, but in untreated hypophysectomized rats 10× more CRF was needed to produce a significant increase in activity. Concomitant daily supplements of rat growth hormone, thyroxine, and corticosterone to the hypophysectomized rats eliminated locomotor activity differences between the two groups. There was no statistically significant difference in locomotor response to either saline, 0.1 μg CRF, 1.0 μg CRF or 10.0 μg CRF in the group of animals receiving hormonal supplements. These results demonstrate that CRF can produce behavioral activation in rats independently of its effects on releasing hormones from the pituitary gland.     

Effects of methyl-eugenol administration on behavioral models related to depression and anxiety, in rats

Croton zehntneri (Cz) is a popular plant in Brazilian folk medicine. Recently, the use of its essential oil showed depressive activity response in the central nervous system (CNS). Chemical studies show that the main compound of this oil is the methyl-eugenol (ME). This work seeks to evaluate the ME activity in behavioral models of depression and anxiety, in the rat. Male rats (60 days old) were divided into four groups (n = 10) and treated with doses of 1.0, 3.0 and 10.0 ml/100 g body wt., v.o., of ME (experimental) and saline (control). One hour after treatment, they were observed in the forced swimming test and 15 min later in the open-field test. A decrease was observed in the immobility time during the forced swimming test for all experimental groups, in comparison with control group (C = 168.8 +/- 27.3; 1.0 microl = 139.1 +/- 23.5; 3.0 microl = 137.2 +/- 18.7 and 10.0 microl = 139.8 +/- 23.6). The open-field results showed no differences in comparison to the control group. The same was observed for social interaction, plus-maze and holeboard tests, suggesting no alterations in anxiety behavior. These data suggest that ME administration induced antidepressive CNS alterations, expressed by the smallest immobility in the swimming model, and not of a level able to alter motor and exploratory activity in the open-field. The absence of effects observed in the open-field can be a result of the experimental contingency, taking low anxiety levels. These data are in contradiction to observations with Cz essential oil in these models.     

Impairment of long-term depression induced by chronic brain inflammation in rats

Although deficits in synaptic plasticity have been identified in aged or neuroinflamed animals with memory impairments, few studies have examined the cellular basis of plasticity in such animals. Here, we examined whether chronic neuroinflammation altered long-term depression (LTD) and studied the underlying mechanism of LTD impairment by neuroinflammation. Chronic neuroinflammation was induced by administration of lipopolysaccharide (LPS) to the fourth ventricle. Excitatory postsynaptic potentials were recorded extracellularly in the rat hippocampal CA1 area to examine alterations in synaptic plasticity. Chronic administration of LPS induced remarkable memory impairment in the Morris water maze test. N-methyl-d-aspartate receptor (NMDAR)-dependent LTD was almost absent in LPS-infused animals. The AMPA receptor (AMPAR)-mediated synaptic response was reduced in the LPS-infused group. These results suggest that reduction in NMDAR-dependent LTD might arise because of alterations in postsynaptic AMPARs as well as NMDARs and that such changes may be present in mild and early forms of Alzheimer-type dementia.     

Inbreeding depression and outbreeding depression in Digitalis purpurea: optimal outcrossing distance in a tetraploid

An optimal crossing distance exists within plant populations if inbreeding and outbreeding depression operate simultaneously. In a population of tetraploid Digitalis purpurea, maternal plants were pollinated with donors at four distances: 0 (self-pollination), 1, 6 and 30 m. Lifetime fitness of F1 progeny was investigated in greenhouse experiments, and significant inbreeding and outbreeding depression were detected at five vs. three life history traits. Inbreeding depression increased at later life stages, whereas outbreeding depression was relatively constant. The existence of within-population outbreeding depression suggests substantial genetic structuring at moderate distances in D. purpurea, and corroborates recent findings of significant outbreeding depression in F1 progeny in polyploids. The moderate inbreeding depression found in this predominately outcrossing population supports the notion that effects of inbreeding are less severe in polyploids than in diploids.     

Knockout of the norepinephrine transporter and pharmacologically diverse antidepressants prevent behavioral and brain neurotrophin alterations in two chronic stress models of depression

Diverse factors such as changes in neurotrophins and brain plasticity have been proposed to be involved in the actions of antidepressant drugs (ADs). However, in mouse models of depression based on chronic stress, it is still unclear whether simultaneous changes in behavior and neurotrophin expression occur and whether these changes can be corrected or prevented comparably by chronic administration of ADs or genetic manipulations that produce antidepressant-like effects such as the knockout of the norepinephrine transporter (NET) gene. Here we show that chronic restraint or social defeat stress induce comparable effects on behavior and changes in the expression of neurotrophins in depression-related brain regions. Chronic stress caused down-regulation of BDNF, nerve growth factor, and neurotrophin-3 in hippocampus and cerebral cortex and up-regulation of these targets in striatal regions. In wild-type mice, these effects could be prevented by concomitant chronic administration of five pharmacologically diverse ADs. In contrast, NET knock out (NETKO) mice were resistant to stress-induced depressive-like changes in behavior and brain neurotrophin expression. Thus, the resistance of the NETKO mice to the stress-induced depression-associated behaviors and biochemical changes highlight the importance of noradrenergic pathways in the maintenance of mood. In addition, these mice represent a useful model to study depression-resistant behaviors, and they might help to provide deeper insights into the identification of downstream targets involved in the mechanisms of antidepressants.     

Increase in Rat Adrenal Phenylethanolamine N-Methyltransferase mRNA Level Caused by Immobilization Stress Depends on Intact Pituitary - Adrenocortical Axis

Abstract: The effects of a single and of repeated immobilization stress on the expression of the final enzyme involved in epinephrine biosynthesis, phenylethanolamine N -methyltransferase (PNMT), are described. A single immobilization (whether lasting 5 or 120 min) caused a severalfold increase of the adrenal PNMT mRNA level as measured 2 h after the beginning of the procedure. This elevation was of a transient nature, peaked 3–6 h after the 2-h immobilization, and returned to control values by 12 h after the stress. When the animals were immobilized for 2 h/day for seven consecutive days, an increase in content of PNMT mRNA of a similar magnitude was observed, which persisted for at least 2 days after the seventh immobilization. The immobilization-induced increase was completely abolished in hypophysectomized animals, whereas adrenal denervation failed to prevent it. These data suggest that the immobilization-induced increase in adrenal PNMT mRNA level depends primarily on pituitary-adrenocortical regulation.     

EEG Correlates of Dream Recall in Depressed Outpatients and Healthy Controls

The present study explored EEG correlates of dream recall in 17 symptomatic, unmedicated depressed patients and in 19 healthy adults. EEG segments from the last 30 minutes of sleep, from the five minutes following morning awakening, and the absolute difference between sleep and waking EEG were contrasted between the two groups of participants during successful dream recall and during no recall. Period amplitude analysis was used to quantify EEG frequencies. Increased high-frequency beta incidence in the right hemisphere and amplitude in both hemispheres during sleep were associated with dream recall in both patient and control groups. Depressed patients also showed higher delta amplitude in both hemispheres during sleep associated with recall, but this effect did not reach significance. With regard to the changes between sleep and wakefiilness, a smaller change in right hemisphere beta and delta incidence characterized successful recall in healthy controls. By contrast, those with depression showed recall success when the sleep/wake shifts in right hemisphere beta and delta incidence were larger. Recall failure was characterized by small EEG shifts from sleep to wakefulness in the depressed group. The same effects were observed for beta and delta amplitude measures, except that healthy controls showed a large shift in delta amplitude in the sleep-wake transition during successful recall but not during recall failure. Recall in those with depression was associated with a dramatic shift in left hemisphere delta amplitude. These findings provide support for Koukkou and Lehmann's (1983, 1993) state-shift hypothesis of dream recall in healthy controls (except for left hemisphere delta amplitude) but not in the depressed. It appears that in order to recall a dream, depressed patients must undergo larger shifts in brain activity and perhaps a different pattern of reorganization of EEG frequencies than controls. This finding may account for the low rates of recall reported previously in this clinical group.     

Inbreeding and outbreeding depression in Daphnia

Egg-to-adult viability of sexual offspring in Daphnia magna is lower for selfed (average: 43.0%) than for outcrossed families (average: 74.7%). This suggests that intraclonal mating is not the rule in Daphnia populations. For a given family, hatching rate of eggs resulting from interpopulation crosses is lower than for intrapopulation crosses. This breakdown in hatching responses may result in the effective gene flow between Daphnia populations being severely reduced, offering an explanation for the apparent paradox of genetic differentiation of Daphnia populations in spite of efficient dispersal.