大鼠内侧隔区预损毁对海马迟发性神经元死亡的影响

目的：探讨乙酰胆碱（ACh)对短暂性全脑缺血再灌后海马迟发性神经元死亡（DND）的作用。方法：80只健康雄性Wistar大鼠随机分为5组。I组：手术对照组；Ⅱ组：单纯内侧隔区（MS）损毁组；Ⅲ组：单纯脑缺血再灌注组；Ⅳ组：MS假性损毁脑缺血再灌注组；Ⅴ组：MS预损毁脑缺血再灌注组，动物先行MS损毁，第15d再行血管阻断，使脑缺血20min，并于恢复灌注72h后处死，将脑采用常规石蜡包埋、切片，Nissle、HE和Tunel免疫组化染色，在光镜下观测计数海马的神经元数。结果：（1）DND细胞主要发生在各缺血再灌注组（Ⅲ，Ⅳ，Ⅴ组）的海马CA1区，其他各区未发现明显变化；（2）V组较Ⅲ，Ⅳ组DNA明显减轻，差异有统计学意义（P＜0．05）。结论：ACh参与短暂性全脑缺血再灌后海马CA1区迟发性神经元损伤过程，MS预损毁能使死亡细胞明显减少。     

Similarities vs. differences in place learning and circadian activity in rats after fimbria-fornix section or ibotenate removal of hippocampal cells

Damage to either the fimbria-fornix or to the hippocampus can produce a deficit in spatial behavior and change in locomotor activity but the extent to which the two kinds of damage are comparable is not known. Here we contrasted the effects of cathodal sections of the fimbria-fornix with ibotenic acid lesions of the cells of the hippocampus (Ammon's horn and the dentate gyrus) on place learning in a swimming pool and on circadian activity. Rats in both ablation groups were impaired relative to control rats in learning a single place response but they did acquire the response as measured by swim latencies, errors, and by enhanced searching on probe trials. They were also more active than the control group on the test of activity. Nevertheless, the fimbria-fornix group was initially more impaired on learning and was more active than the hippocampal group. Analysis of the strategies used in learning indicated that the lesion groups were very similar to each other but different from the control group especially in that at asymptotic performance, rats in both lesion groups made rather tight loops as they swam toward the platform. This strategy likely contributed to the greater proportion of time they spent swimming in the correct quadrant on the subsequent probe trial. These findings confirm that rats with fimbria-fornix or hippocampal damage display impairments in place learning and are hyperactive but also show that there are lesion differences. The results are discussed with respect to the relative effectiveness of the lesions and the possibility that fibers in the fimbria-fornix may mediate some functions that are not attributable to the hippocampus. © 1995 Wiley-Liss, Inc.     

The fibroblast growth factor system and mood disorders.

Recent evidence now suggests the involvement of the fibroblast growth factor (FGF) system in mood disorders. Specifically, several members of the FGF family have been shown to be dysregulated in individuals with major depression. In this review, we will introduce the FGF system in terms of structure and function during development, in adulthood, and in various regions and cell types. We will also review the FGF system as a mediator of neural plasticity. Furthermore, this review will summarize animal as well as human studies. The majority of animal studies have focused on stress, environmental enrichment, pharmacological manipulations, and the hippocampus. By contrast, human studies have focused on volumetric measurements, antidepressant literature, and, most recently, post-mortem microarray experiments. In summary, a reduced tone in the FGF system might alter brain development or remodeling and result in a predisposition or vulnerability to mood disorders, including major depression.     

Corticosterone-induced inhibition of gliogenesis in rat hippocampus is counteracted by electroconvulsive seizures.

BACKGROUND: Volumetric changes and glial pathology have been reported in the central nervous system (CNS) of patients with depressive disorder, an illness often associated with elevated glucocorticoid levels. Glucocorticoids reduce gliogenesis in the adult rat CNS. Electroconvulsive seizure (ECS)-treatment, an animal model for the antidepressant treatment electroconvulsive therapy, can enhance proliferation of glial cells. This study examined glial cell proliferation in response to ECS in rats whose glucocorticoid levels were elevated to mimic the conditions seen in depression. METHODS: Rats were injected daily for seven days with either corticosterone or vehicle. ECS- or sham- treatment was given once daily during the first five days. Proliferating cells in the hippocampus were labeled with bromodeoxyuridine and analyzed for co-labeling with the glial cell markers NG2, Ox42, S-100beta and Rip. RESULTS: ECS counteracted the glucocorticoid-induced inhibition of NG2+, Ox42+ and Rip+ cell proliferation, and the gliogenesis rate was restored to baseline levels. Volumetric changes in rats treated with ECS were detected. CONCLUSIONS: Our results show that ECS-treatment affects the proliferation of glial cells even in the presence of elevated levels of glucocorticoids. This result adds to an increasing number of studies suggesting that antidepressant treatment can counteract degenerative processes associated with major depression.     

绞股蓝总皂苷对血管性痴呆大鼠大脑皮层及海马的影响

目的 观察绞股蓝总皂苷（GP）对血管性痴呆大鼠大脑皮层及海马的DNA和RNA的影响。方法 采用改良的Pulsinelli-4血管阻断（4－VO）方法建立大鼠血管性痴呆模型，用吖啶橙染色法进行GP对血管性痴呆大鼠大脑皮层及海马的DNA和RNA保护作用的研究。结果 与正常对照组比较，血管性痴呆大鼠大脑皮层及海马的DNA和RNA吖啶橙染色后的荧光强度（反映DNA和RNA含量）明显减弱，GP200mg/kg ig给药组大脑皮层及海马的DNA和RNA吖啶橙染色后的荧光强度强于血管性痴呆模型组，与正常对照组相似。结论 GP可明显减轻血管性痴呆大鼠大脑皮层及海马的DNA和RNA损伤。     

Interneuron-specific Ca2+ Responses Linked to Metabotropic -and lonotropic Glutamate Receptors in Rat Hippocampal Slices

Glutamate-mediated regulation of intracellular Ca²⁺ levels was examined in different populations of CA1 interneurons, using confocal microscopy and the Ca²⁺ indicator fluo 3-AM in rat hippocampal slices. Interneurons in basal [stratum oriendalveus (OA)] and apical [strata radiatum and lacunosum-moleculare (R/LM)] dendritic layers responded heterogeneously to glutamate. In control medium, OA interneurons responded mostly with oscillatory Ca²⁺ responses, which consisted of a large Ca²⁺ transient and successive smaller elevations. R/LM interneurons responded mostly with biphasic responses, characterized by an initial large transient and a secondary prolonged elevation. Other interneurons in both R/LM and OA responded with transient elevations in Ca²⁺ levels. lonotropic glutamate receptor antagonists (±)2-amino-5-phosphonopentanoic acid and 6-cyano-7-nitro-quinoxaline-2,3-dione reduced peak Ca²⁺ responses in OA and R/LM cells, and blocked biphasic responses in R/LM interneurons. The metabotropic glutamate receptor antagonist (RS)-α-methyl-4-carboxyphenylglycine reduced peak Ca²⁺ responses only in OA interneurons, and prevented oscillatory responses. In low Ca²⁺ medium, peak responses were reduced in R/LM but not in OA interneurons, and oscillatory responses were absent. Combination of ionotropic and metabotropic receptor antagonists blocked all glutamate-evoked Ca²⁺ responses. Activation of different types of glutamate receptors may thus produce heterogeneous Ca²⁺ signals in subpopulations of CA1 interneurons. lonotropic receptors may generate biphasic responses in interneurons in apical dendritic layers, whereas combined activation of metabotropic and ionotropic receptors may trigger oscillatory responses in interneurons of basal dendritic layers. These heterogeneous Ca²⁺ responses indicate that glutamate-mediated Ca²⁺ processes and second messenger systems differ in subpopulations of hippocampal interneurons and suggest possible postsynaptic functional specialization of interneurons.     

THE EFFECT OF GYNOSTEMMA ON LEARNING AND MEMORY OF RATS

Gynostemma(Gynostemmapentaphallum)canimprovelearningandmemoryofrats,butthemech-anismisunclear.Theprocessionoflearningandmemo-ryisdivdedintofourparts:acqusition,retention,recog-nitionandrecall.Manypartsofthebraintakepartinacqustion,suchasleftprefrontalcort…     

Corticosterone treatment differentially affects adrenocorticoid receptors expression and binding in the hippocampus and spinal cord of the rat

We have studied the immediate and long-term effects of high doses of corticosterone (CORT) on mRNA expression and binding properties of mineralocorticoid receptor and glucocorticoid receptor in the hippocampus and spinal cord of rats. Animals were treated with corticosterone (10 mg/d subcutaneously) for 21 consecutive days, and mineralocorticoid and glucocorticoid receptors were studied either 24 h or 2 wk after the last injection. Major results show that corticosterone treatment reduces mineralocorticoid and glucocorticoid receptor maximum binding capacity (B _max) in both the hippocampus and spinal cord and that this reduction is partially reversed after cessation of treatment. With respect to mRNA expression, in the hippocampus recovery after cessation of treatment is complete. By contrast, in the spinal cord, mineralocorticoid receptor mRNA expression is irreversibly increased after treatment, but the glucocorticoid receptor mRNA level remains unaffected during and after treatment. Thus, these data suggest the presence of distinct regulatory mechanisms for adrenocorticoid receptors in rat brain and spinal cord, in response to long-term exposure to high levels of circulating corticosterone and after recovery from treatment.     

5-HT1A agonists induce hippocampal theta activity in freely moving cats: role of presynaptic 5-HT1A receptors

Electrical activity in the dorsal hippocampus was recorded in freely moving cats in response to intravenous administration of 5-HT_1A agonist and antagonist drugs. Administration of low doses of the selective 5-HT_1A agonists 8-OH-DPAT (5–20 μg/kg) and ipsapirone (20–100 μg/kg) produced rhythmic slow activity (theta) in the hippocampal EEG within 30 s. Similar effects were observed with BMY 7378 (20 and 100 μg/kg), which acts as an agonist at presynaptic (somatodendritic) 5-HT_1A receptors and as an antagonist at postsynaptic 5-HT_1A receptors. Power spectral analyses showed that all three compounds produced a dose-dependent increase in the EEG power occurring in the theta frequency band (3.5–8.0 Hz) as a proportion of total power from 0.25 to 30.0 Hz (relative theta power). The increase in relative theta power produced by 8-OH-DPAT (20 μg/kg) was greatly attenuated by spiperone (1 mg/kg), a highly effective 5-HT_1A autoreceptor antagonist. Administration of spiperone alone had no significant effect on relative theta power. These results are discussed in relationship to the effects of these drugs on serotonergic neuronal activity. Our results suggest that preferential activation of presynaptic 5-HT_1A receptors, and subsequent inhibition of serotonin neurotransmission, facilitates the appearance of hippocampal theta activity in awake cats.     

Behavioural effects of adenosine locally applied into ventral hippocampus of adult male rats

Summary The possible effects of Adenosine (AD), locally applied into the ventral Hippocampus (HPCv) on the expression of general motor activity and some stereotyped behaviours were studied in adult male rats. Locomotion display was recorded in a hole-board equiped with automatic infrared animal activity detectors. Stereotyped behaviours were measured by direct inspection by two observers. Animals were implanted with microinjection cannulae into the HPCv and 72 h later they were injected with saline, or increasing doses of AD. In one experiment rats were microinjected once with saline or Adenosine and general motor activity and exploration were examined. In other experiment, rats were injected into the HPCv twice with saline, the AD-receptors antagonist 1,3-dipropil-methyl-xanthine (DMX) or AD and only stereotyped behaviours were examined. Results of Experiment 1 showed that the 40 nMol dose of AD was significantly effective to inhibit by about 30% several motor activities such as vertical, horizontal and ambulatory behaviours. Results of Experiment 2, showed that grooming was not modified by AD but the dose of 10 nMol increased the time of immobility by about 3 times over controls. DMX was able to block completely the AD effects on immobility. The present results suggest that in the rat AD might modulate the hippocampal-mediated expression of some motor and stereotyped behaviours induced by unknown environments.