Effect of tube feeding on hippocampal-dependent memory in SAMP1 mice

This study examined the effect of tube feeding on hippocampal Fos induction and spatial performance in a water maze task in senescenceaccelerated mice (SAMP1). Tube feeding accelerated the age-related decline in spatial memory and decreased Fos induction in the hippocampal CA1 region in aged SAMP1 mice. The results suggest that tube feeding in aged SAMP1 mice reduces input activity in the hippocampus, thereby leading to senile memory deficits.     

Investigations into migraine pathogenesis: time course for effects of m-CPP, BW723C86 or glyceryl trinitrate on appearance of Fos-like immunoreactivity in rat trigeminal nucleus caudalis (TNC)

Clinical and preclinical studies suggest that 5-HT and nitric oxide (NO) mobilization within the trigeminovascular system is fundamental to the initiation of migraine attacks., e.g. m-chlorophenylpiperazine (m-CPP) and glyceryl trinitrate (GTN) induce headache in humans. 5-HT2B receptors are known to mediate NO-dependent vasorelaxation in peripheral blood vessels, raising the possibility that this receptor is implicated in the pathogenesis of the disease. Therefore, we measured the effects of 5-HT2B agonists (m-CPP or BW723C86) or GTN on trigeminal nerves by quantifying Fos expression in the rat TNC. m-CPP (0.1 mg/kg, i.v.) induced time-dependent elevations in Fos-LI in the rat TNC 2 h and 8 h after injection. In contrast, neither intravenous GTN (0.5 microg/kg per min, infused 20 min) nor BW723C86 (0.1 mg/kg, i.v.) increased Fos-LI at 2 h or 8 h after administration. These data are not consistent with the involvement of the 5-HT2B/2C receptors or NO in trigeminovascular activation, and by inference migraine, and suggest the contribution of some other unidentified pathway.     

脑缺血再灌注后fos蛋白免疫组化与脑脉宝保护作用

目的脑脉宝是一种具有抗脑缺血再灌注损伤作用的中药复方制剂，本实验观察大鼠脑缺血再灌注后ｃ－ｆｏｓ蛋白表达产物变化，并探讨脑脉宝的保护作用是否与抑制ｆｏｓ蛋白表达有关。方法采用四血管阻断法制成脑缺血３０ｍｉｎ，再灌注３０ｍｉｎ模型，应用免疫组化法观察神经元中ｃ－ｆｏｓ蛋白的表达。结果脑缺血再灌注组鼠脑皮层和海马中ｆｏｓ样免疫活性显著升高，预先给予脑脉宝可抑制其表达。结论核相关性ｆｏｓ蛋白表达是脑缺血再灌注损伤后一种敏感的细胞反应标志物，并提供了一种评价药物疗效的方法。脑脉宝可抑制ｆｏｓ蛋白表达，这可能是其治疗缺血性脑血管病有效，及对缺血再灌注损伤发挥保护作用的分子机理之一。     

Moderate and severe perinatal asphyxia induces differential effects on cocaine sensitization in adult rats

Perinatal asphyxia (PA) increases the likelihood of suffering from dopamine‐related disorders, such as ADHD and schizophrenia. Since dopaminergic transmission plays a major role in cocaine sensitization, the purpose of this study was to determine whether PA could be associated with altered behavioral sensitization to cocaine. To this end, adult rats born vaginally (CTL), by caesarean section (C+), or by C+ with 15 min (PA15, moderate PA) or 19 min (PA19, severe PA) of global anoxia were repeatedly administered with cocaine (i.p., 15 mg/kg) and then challenged with cocaine (i.p., 15 mg/kg) after a 5‐day withdrawal period. In addition, c‐Fos, FosB/ΔFosB, DAT, and TH expression were assessed in dorsal (CPu) and ventral (NAcc) striatum. Results indicated that PA15 rats exhibited an increased locomotor sensitization to cocaine, while PA19 rats displayed an abnormal acquisition of locomotor sensitization and did not express a sensitized response to cocaine. c‐Fos expression in NAcc, but not in CPu, was associated with these alterations in cocaine sensitization. FosB/ΔFosB expression was increased in all groups and regions after repeated cocaine administration, although it reached lower expression levels in PA19 rats. In CTL, C+, and PA15, but not in PA19 rats, the expression of TH in NAcc was reduced in groups repeatedly treated with cocaine, independently of the challenge test. Furthermore, this reduction was more pronounced in PA15 rats. DAT expression remained unaltered in all groups and regions studied. These results suggest that moderate PA may increase the vulnerability to drug abuse and in particular to cocaine addiction. Synapse 67:553–567, 2013. © 2013 Wiley Periodicals, Inc.     

Diurnal rhythms in neural activation in the mesolimbic reward system: critical role of the medial prefrontal cortex

Previous evidence suggests a circadian modulation of drug‐seeking behavior and responsiveness to drugs of abuse. To identify potential mechanisms for rhythmicity in reward, a marker of neural activation (cFos) was examined across the day in the mesolimbic reward system. Rats were perfused at six times during the day [zeitgeber times (ZTs): 2, 6, 10, 14, 18, and 22], and brains were analysed for cFos and tyrosine hydroxylase (TH)‐immunoreactive (IR) cells. Rhythmic expression of cFos was observed in the nucleus accumbens (NAc) core and shell, in the medial prefrontal cortex (mPFC), and in TH‐IR and non‐TH‐IR cells in the ventral tegmental area (VTA), with peak expression during the late night and nadirs during the late day. No significant rhythmicity was observed in the basolateral amgydala or the dentate gyrus. As the mPFC provides excitatory input to both the NAc and VTA, this region was hypothesised to be a key mediator of rhythmic neural activation in the mesolimbic system. Hence, the effects of excitotoxic mPFC lesions on diurnal rhythms in cFos immunoreactivity at previously observed peak (ZT18) and nadir (ZT10) times were examined in the NAc and VTA. mPFC lesions encompassing the prelimbic and infralimbic subregions attenuated peak cFos immunoreactivity in the NAc, eliminating the diurnal rhythm, but had no effect on VTA rhythms. These results suggest that rhythmic neural activation in the mesolimbic system may contribute to diurnal rhythms in reward‐related behaviors, and indicate that the mPFC plays a critical role in mediating rhythmic neural activation in the NAc.     

The pattern of Fos expression in the spinal dorsal horn following acute noxious mechanical stimulation of bone

Little is known of the spinal mechanisms that mediate bone nociception. The aim of this study was to determine the pattern of neuronal activation in the spinal dorsal horn following acute noxious mechanical stimulation of bone. This was achieved by examining Fos expression in the spinal dorsal horn following acute, noxious mechanical stimulation of the rat tibia. Noxious mechanical stimuli were applied by bone drilling and raising tibial intra-osseous pressure. Control experiments consisted of surgery to expose the tibia. There was a significant increase in the number of Fos-like immunoreactive (Fos-LI) nuclei in the superficial, ipsilateral dorsal horn of animals in the bone drilling and pressure groups relative to animals of the control group at spinal cord segments L3 and L4 (P < 0.05). The number of Fos-LI nuclei in the deep dorsal horn was always lower than the number in the superficial dorsal horn (significant at L3 but not L4; P < 0.05). Whilst there appeared to be a small increase in the number of Fos-LI nuclei in the ipsilateral deep dorsal horn of bone drilling and pressure groups relative to the ipsilateral deep dorsal horn control group at both L3 and L4 segments, no significant effect was observed (P > 0.05). The present study implicates the superficial dorsal horn of the spinal cord as a region of interest in studies of acute bone pain, and highlights the notion that spinal mechanisms that mediate bone nociception may be different to those that mediate nociception of cutaneous and visceral origin.     

彩色多普勒超声对胎鼠大脑Fos蛋白表达影响的实验研究

目的 探讨诊断用彩色多普勒超声对胎鼠中枢神经系统的影响。方法 利用彩超照射孕18天大鼠子宫体表投影区，滑行照射30min，间隔不同时间留取胎鼠脑组织标本，分为照射后即刻、30min、2h、4h、8h及24h共6组及各自的对照组。应用免疫组化方法检测Fos蛋白的表达及出现的时间顺序。结果 ①照射后即刻及30min组仅见极少量着色浅淡的Fos阳性细胞，照射后2h出现密集分布的深染Fos阳性细胞，照射后4h及8h阳性细胞数逐渐下降，而照射后24h再次出现Fos蛋白高表达。②对照组各时间点均未见着色的Fos阳性细胞。结论 诊断用的彩超照射孕鼠30min，可激活胎鼠脑组织c-fos基因，并诱导其转录和表达，其高表达时间出现于照射后2h及24h。     

Elucidation of the anatomy of a satiety network: Focus on connectivity of the parabrachial nucleus in the adult rat

We hypothesized that brain regions showing neuronal activation after refeeding comprise major nodes in a satiety network, and tested this hypothesis with two sets of experiments. Detailed c‐Fos mapping comparing fasted and refed rats was performed to identify candidate nodes of the satiety network. In addition to well‐known feeding‐related brain regions such as the arcuate, dorsomedial, and paraventricular hypothalamic nuclei, lateral hypothalamic area, parabrachial nucleus (PB), nucleus of the solitary tract and central amygdalar nucleus, other refeeding activated regions were also identified, such as the parastrial and parasubthalamic nuclei. To begin to understand the connectivity of the satiety network, the interconnectivity of PB with other refeeding‐activated neuronal groups was studied following administration of anterograde or retrograde tracers into the PB. After allowing for tracer transport time, the animals were fasted and then refed before sacrifice. Refeeding‐activated neurons that project to the PB were found in the agranular insular area; bed nuclei of terminal stria; anterior hypothalamic area; arcuate, paraventricular, and dorsomedial hypothalamic nuclei; lateral hypothalamic area; parasubthalamic nucleus; central amygdalar nucleus; area postrema; and nucleus of the solitary tract. Axons originating from the PB were observed to closely associate with refeeding‐activated neurons in the agranular insular area; bed nuclei of terminal stria; anterior hypothalamus; paraventricular, arcuate, and dorsomedial hypothalamic nuclei; lateral hypothalamic area; central amygdalar nucleus; parasubthalamic nucleus; ventral posterior thalamic nucleus; area postrema; and nucleus of the solitary tract. These data indicate that the PB has bidirectional connections with most refeeding‐activated neuronal groups, suggesting that short‐loop feedback circuits exist in this satiety network. J. Comp. Neurol. 524:2803–2827, 2016. © 2016 Wiley Periodicals, Inc.     

Neuropeptide W as a stress mediator in the hypothalamus

Neuropeptide W (NPW) was isolated and found to be an endogenous peptide ligand for the orphan receptors GPR7 and GPR8. Centrally administered NPW caused a dose-dependent increase in corticosterone levels in rats. This observation indicates that NPW may play an important role in the hypothalamic organization of the endocrine response to stress. We examined the effects of immobilization stress and cold exposure on NPW-containing neurons in the hypothalamus of the rat, using dual immunostaining for NPW and Fos. In addition, to analyze the function of NPW, we studied the effect of intracerebroventricular (icv) NPW administration on Fos protein accumulation in the brain. Double immunohistochemistry for NPW and Fos showed that the percentage of Fos expression in the NPW-immunoreactive cells of the perifornical nucleus was significantly increased by immobilization stress compared with that in nonstressed rats. Similarly, the results indicated that cold exposure activates NPW-immunoreactive neurons in the perifornical nucleus. An icv administration of NPW resulted in significant Fos expression in the paraventricular nucleus, as compared with saline-infused controls. These results suggest that NPW is related to stress-responsive signal transduction, and that NPW may modulate the hypothalamus-pituitary-adrenal axis.     

Kainic acid-induced early genes activation and neuronal death in the medial extended amygdala of rats

The medial extended amygdala modulates pheromonal perception, influencing emotional and social behavior. As the amygdala is part of neuronal circuits that are very sensitive to excitability, its neurons are targets of seizures in temporal lobe epilepsy. It has been suggested that the hippocampus is strongly involved this pathology. There is less consistent information, however, on the effects of this disease in the amygdala. The effects of status epilepticus on the medial extended amygdala were analyzed by immunohistochemistry for neural stress and by the amino-cupric-silver technique for neuronal death in rats after kainic acid (KA) administration. Sixty adult Wistar male rats were used. Thirty animals received an injection of KA, and 30 were injected with saline. After 2, 4, 12, 24 and 48 h survival the brains were stained for Fos and FosB and for neuronal death.In the present study we show that KA induces Fos and FosB expression in neurons of the medial extended amygdala after 2, 4-48 h, with time courses that are different between them and from control animals. While Fos-IR peaks at 2-4 h post KA and then decreases, FosB-IR increases in the same period reaching its highest expression at 24-48 h. Moreover, KA injection produced massive neuronal death with a peak at 24 h. This neurodegeneration paralleled FosB-IR protein expression.These findings show that KA produces neuronal stress and activation of early genes and neuronal death in the medial extended amygdala, demonstrating the vulnerability of its neurons to the epileptogenic effects of KA.