Ethanol Extract of Chinese Propolis Facilitates Functional Recovery of Locomotor Activity after Spinal Cord Injury

An ethanol extract of Chinese propolis (EECP) was given intraperitoneally to rats suffering from hemitransection of half of their spinal cord (left side) at the level of the 10th thoracic vertebra to examine the effects of the EECP on the functional recovery of locomotor activity and expression of mRNAs of inducible nitric oxide (NO) synthase (iNOS) and neurotrophic factors in the injury site. Daily administration of EECP after the spinal cord injury ameliorated the locomotor function, which effect was accompanied by a reduced lesion size. Furthermore, the EECP suppressed iNOS gene expression, thus reducing NO generation, and also increased the expression level of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the lesion site, suggesting that the EECP reduced the inflammatory and apoptotic circumstances through attenuation of iNOS mRNA expression and facilitation of mRNA expression of neurotrophins in the injured spinal cord. These results suggest that Chinese propolis may become a promising tool for wide use in the nervous system for reducing the secondary neuronal damage following primary physical injury

Antidepressant-Like Activity of 10-Hydroxy-Trans-2-Decenoic Acid, a Unique Unsaturated Fatty Acid of Royal Jelly, in Stress-Inducible Depression-Like Mouse Model

Symptoms of depression and anxiety appeared in mice after they had been subjected to a combination of forced swimming for 15 min followed by being kept in cages that were sequentially subjected to leaning, drenching, and rotation within 1-2 days for a total of 3 weeks. The animals were then evaluated by the tail-suspension test, elevated plus-maze test, and open-field test at 1 day after the end of stress exposure. Using these experimental systems, we found that 10-hydroxy-trans-2-decenoic acid (HDEA), an unsaturated fatty acid unique to royal jelly (RJ), protected against the depression and anxiety when intraperitoneally administered once a day for 3 weeks simultaneously with the stress loading. Intraperitoneally administered RJ, a rich source of HDEA, was also protective against the depression, but RJ given by the oral route was less effective. Our present results demonstrate that HDEA and RJ, a natural source of it, were effective in ameliorating the stress-inducible symptoms of depression and anxiety

2-Decenoic Acid Ethyl Ester, a Compound That Elicits Neurotrophin-like Intracellular Signals, Facilitating Functional Recovery from Cerebral Infarction in Mice

In our previous study, we found that trans-2-decenoic acid ethyl ester (DAEE), a derivative of a medium-chain fatty acid, elicits neurotrophin-like signals including the activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) in cultured mouse cortical neurons. Here, we examined the efficacy of intraperitoneal administration of DAEE on the treatment of a mouse model of the cerebral infarction caused by unilateral permanent middle cerebral artery occlusion (PMCAO). DAEE-treatment (100 μg/kg body weight injected at 0.5, 24, 48, 72 h after PMCAO) significantly restored the mice from PMCAO-induced neurological deficits including motor paralysis when evaluated 48, 72, and 96 h after the PMCAO. Furthermore, DAEE facilitated the phosphorylation of ERK1/2 on the infarction side of the brain when analyzed by Western immunoblot analysis, and it enhanced the number of phosphorylated ERK1/2-positive cells in the border areas between the infarction and non-infarction regions of the cerebral cortex, as estimated immunohistochemically. As the infarct volume remained unchanged after DAEE-treatment, it is more likely that DAEE improved the neurological condition through enhanced neuronal functions of the remaining neurons in the damaged areas rather than by maintaining neuronal survival. These results suggest that DAEE has a neuro-protective effect on cerebral infarction

免疫系に関わる因子が大脳皮質神経細胞層の構築に及ぼす影響

自閉症を含む発達障害や統合失調症は様々な臨床症状を呈するが、認知機能障害を病態の中核症状としている。患者の剖検大脳皮質において微細構造の異常が報告されており、認知を含む高次脳機能障害の一因であると考えられている。また、これらの精神疾患患者の脳内では免疫系サイトカインの発現プロファイルが変化しており、病態脳形成に免疫系異常が関与する可能性が示唆されている。そこで本研究では、免疫系に関わる分子が大脳皮質構築過程に及ぼす影響を明らかにし、病態脳形成への関与を検討した。本研究結果から免疫系にかかわる環境因子が胎仔の大脳皮質神経細胞層の構築過程をわずかに修飾することによって、大脳皮質の機能失調にかかわる初期病変を作ることを明らかにした。Clinical symptoms are variable in subjects where cognitive impairments are a major feature with psychiatric, andneurodevelopmental disorders, including schizophrenia and autism. The cerebral cortex plays important roles in cognitive function.Abnormal neuronal morphology and cytoarchitecture of the cerebral cortex are found in postmortem brains from human subjectswith severe psychiatric disorders such as schizophrenia and autism. These impairments are thought to be responsible for theabnormal cognitive functions and behavior of such patients. As immunological dysfunctions have also been reported in schizophrenicor autism patients, it may underlie the development of the psychiatric brain. In this study, we examined how immune-related factorsaffect the development of the cerebral cortex. The results obtained in this study suggest that subtle alterations in the genesis anddevelopment of the cerebral cortex induced by immune-related factors might cause functional disorders of the cerebral cortex

Injury-Induced Accumulation of Glial Cell Line-Derived Neurotrophic Factor in the Rostral Part of the Injured Rat Spinal Cord

Abstract: The spinal cord of a 7-week-old female Wistar rat was hemi-transected at thoracic position 10 with a razor blade, and changes in glial cell line-derived neurotrophic factor (GDNF) protein and mRNA expression levels in the spinal cord were examined. GDNF protein and mRNA expression levels were evaluated by enzyme immunoassay and reverse transcription polymerase chain reaction, respectively. Although GDNF is distributed in the healthy spinal cord from 150 to 400 pg/g tissue in a regionally dependent manner, hemi-transection (left side) of the spinal cord caused a rapid increase in GDNF content in the ipsilateral rostral but not in the caudal part of the spinal cord. On the other hand, injury-induced GDNF mRNA was distributed limitedly in both rostral and caudal stumps. These observations suggest the possibility that increased GDNF in the rostral part is responsible for the accumulation of GDNF that may be constitutively transported from the rostral to caudal side within the spinal cord. Although such local increase of endogenous GDNF protein may not be sufficient for nerve regeneration andInt. J. Mol. Sci. 2012, 13 13485 locomotor improvement, it may play a physiological role in supporting spinal neuron

Neonatal Whisker Trimming Impairs Fear/Anxiety-Related Emotional Systems of the Amygdala and Social Behaviors in Adult Mice

<div><p>Abnormalities in tactile perception, such as sensory defensiveness, are common features in autism spectrum disorder (ASD). While not a diagnostic criterion for ASD, deficits in tactile perception contribute to the observed lack of social communication skills. However, the influence of tactile perception deficits on the development of social behaviors remains uncertain, as do the effects on neuronal circuits related to the emotional regulation of social interactions. In neonatal rodents, whiskers are the most important tactile apparatus, so bilateral whisker trimming is used as a model of early tactile deprivation. To address the influence of tactile deprivation on adult behavior, we performed bilateral whisker trimming in mice for 10 days after birth (BWT10 mice) and examined social behaviors, tactile discrimination, and c-Fos expression, a marker of neural activation, in adults after full whisker regrowth. Adult BWT10 mice exhibited significantly shorter crossable distances in the gap-crossing test than age-matched controls, indicating persistent deficits in whisker-dependent tactile perception. In contrast to controls, BWT10 mice exhibited no preference for the social compartment containing a conspecific in the three-chamber test. Furthermore, the development of amygdala circuitry was severely affected in BWT10 mice. Based on the c-Fos expression pattern, hyperactivity was found in BWT10 amygdala circuits for processing fear/anxiety-related responses to height stress but not in circuits for processing reward stimuli during whisker-dependent cued learning. These results demonstrate that neonatal whisker trimming and concomitant whisker-dependent tactile discrimination impairment severely disturbs the development of amygdala-dependent emotional regulation.</p></div

Neonatal whisker trimming altered stress-induced c-Fos expression pattern in the emotional system of adult mice.

<p>Distribution of c-Fos-expressing neurons in PVN (<b>A</b>) and the amygdala (<b>B</b>) of mice 2 h after being placed on a small elevated platform. The graphs show the density of c-Fos-positive neurons in PVN (<b>C</b>) and the amygdala (<b>D</b>). Scale bar, 100 μm. Values are expressed as the mean ± SE. ***<i>p</i> < 0.001, n.s., no significance versus home cage, #<i>p</i> < 0.05, ###<i>p</i> < 0.001 versus control mice, One-way ANOVA with Tukey’s post hoc test; n = 4 for control and BWT10 mice in their home cages, and n = 5 per group under height stress.</p

Neonatal whisker trimming altered stress-induced c-Fos expression in the frontal cortex of adult mice.

<p>Quantitative analysis revealed significantly higher c-Fos-positive cell density following elevated platform stress in the frontal cortex of control mice, while c-Fos-positive density in the frontal cortex of BWT10 mice was not significantly altered by this stress (<b>A–D</b>). Values are expressed as the mean ± SE. **<i>p</i> < 0.01, ***<i>p</i> < 0.001 versus home cage, #<i>p</i> < 0.05, ##<i>p</i> < 0.01 versus control mice, One-way ANOVA and Tukey’s post hoc test; n = 4 for control and BWT10 mice in their home cages, and n = 5 per group under height stress.</p