In situ direct reprogramming of astrocytes to neurons via polypyrimidine tract-binding protein 1 knockdown in a mouse model of ischemic stroke.

JOURNAL/nrgr/04.03/01300535-202410000-00025/figure1/v/2024-02-06T055622Z/r/image-tiff In situ direct reprogramming technology can directly convert endogenous glial cells into functional neurons in vivo for central nervous system repair. Polypyrimidine tract-binding protein 1 (PTB) knockdown has been shown to reprogram astrocytes to functional neurons in situ. In this study, we used AAV-PHP.eB-GFAP-shPTB to knockdown PTB in a mouse model of ischemic stroke induced by endothelin-1, and investigated the effects of GFAP-shPTB-mediated direct reprogramming to neurons. Our results showed that in the mouse model of ischemic stroke, PTB knockdown effectively reprogrammed GFAP-positive cells to neurons in ischemic foci, restored neural tissue structure, reduced inflammatory response, and improved behavioral function. These findings validate the effectiveness of in situ transdifferentiation of astrocytes, and suggest that the approach may be a promising strategy for stroke treatment.

[A quick solution for lumbar vertebra CT values in different ages and its clinical significance].

OBJECTIVE: To investigate the relationship between the mean CT value and bone density value and explore a rapid and accurate image segmentation method for lumbar CT values in different age groups. METHODS: We randomly collected thin lumbar spine CT scan data from 202 patients stratified by gender and age (at the interval of 10 years). The data of each group were imported into Mimics 14.0 software to obtain independent Mask files using the new image segmentation method. The Mask files were used to fill the empty space and calculate mean, maximum, and minimum CT values. RESULTS: In the age groups of 21-30, 31-40, 41-50, 51-60, and 61-70 years, the male subjects had mean CT values of 424.94 ± 52.23 Hu, 405.59 ± 53.60 Hu, 361.76 ± 53.50 Hu, 344.17 ± 47.76 Hu, and 332.88 ± 58.33 Hu, respectively; the values in the female group were 439.89 ± 50.99 Hu, 448.06 ± 65.89 Hu, 421.43 ± 54.74 Hu, 369.07 ± 78.27 Hu, and 304.98 ± 55.05 Hu, respectively. The mean CT value in men aged 61-70 years was significantly lower than the values in men below 50 years (P<0.05), but comparable with that in those aged 51-60 years (P>0.05); The mean CT value was significantly lower in women aged 51-70 years groups than in those aged below 50 years (P<0.05). CONCLUSIONS: The mean CT values are correlated with the bone density values. The new image segmentation method allows rapid and accurate acquisition of the CT values in the regions of interest. The lumbar mean CT values tend to decrease with age.

Ginsenoside Rb1 attenuates activated microglia-induced neuronal damage.

The microglia-mediated inflammatory reaction promotes neuronal damage under cerebral ischemia/hypoxia conditions. We therefore speculated that inhibition of hypoxia-induced microglial activation may alleviate neuronal damage. To test this hypothesis, we co-cultured ginsenoside Rb1, an active component of ginseng, and cortical neurons. Ginsenoside Rb1 protected neuronal morphology and structure in a single hypoxic culture system and in a hypoxic co-culture system with microglia, and reduced neuronal apoptosis and caspase-3 production. The protective effect was observable prior to placing in co-culture. Additionally, ginsenoside Rb1 inhibited levels of tumor necrosis factor-α in a co-culture system containing activated N9 microglial cells. Ginsenoside Rb1 also significantly decreased nitric oxide and superoxide production induced by N9 microglia. Our findings indicate that ginsenoside Rb1 attenuates damage to cerebral cortex neurons by downregulation of nitric oxide, superoxide, and tumor necrosis factor-α expression in hypoxia-activated microglia.

Changes in topological organization of functional PET brain network with normal aging.

Recent studies about brain network have suggested that normal aging is associated with alterations in coordinated patterns of the large-scale brain functional and structural systems. However, age-related changes in functional networks constructed via positron emission tomography (PET) data are still barely understood. Here, we constructed functional brain networks composed of 90 regions in younger (mean age 36.5 years) and older (mean age 56.3 years) age groups with PET data. 113 younger and 110 older healthy individuals were separately selected for two age groups, from a physical examination database. Corresponding brain functional networks of the two groups were constructed by thresholding average cerebral glucose metabolism correlation matrices of 90 regions and analysed using graph theoretical approaches. Although both groups showed normal small-world architecture in the PET networks, increased clustering and decreased efficiency were found in older subjects, implying a degeneration process that brain system shifts from a small-world network to regular one along with normal aging. Moreover, normal senescence was related to changed nodal centralities predominantly in association and paralimbic cortex regions, e.g. increasing in orbitofrontal cortex (middle) and decreasing in left hippocampus. Additionally, the older networks were about equally as robust to random failures as younger counterpart, but more vulnerable against targeted attacks. Finally, methods in the construction of the PET networks revealed reasonable robustness. Our findings enhanced the understanding about the topological principles of PET networks and changes related to normal aging.

Age-related differences and relationships between elements in human amygdala and other limbic system or basal ganglia.

To elucidate the compositional changes of the amygdala with aging, the authors investigated age-related differences of elements in human amygdalae. In addition, the relationships between the amygdala and other brain regions were investigated from a viewpoint of elements. After ordinary dissections at Nara Medical University were finished, the amygdalae were removed from the cerebra of the subjects who consisted of 22 men and 23 women, ranging in age from 70 to 101 years. In addition, the hippocampus, dentate gyrus, mammillary body of the limbic system and the caudate nucleus, putamen, and globus pallidus of the basal ganglia were also removed from the identical cerebra. After the brain samples were incinerated with nitric acid and perchloric acid, the element contents were determined by inductively coupled plasma-atomic emission spectrometry. It was found that both the Ca and Mg contents increased significantly in the amygdalae with aging, but the other five element contents (P, S, Zn, Fe, and Na) did not change significantly in the amygdalae with aging. Regarding the relationships among elements, very significant or significant direct correlations were found among the Ca, P, and Mg contents in the amygdalae. To explore the relationships between the amygdala and either other limbic system or basal ganglia, the correlations between seven elements of the amygdala and hippocampus, dentate gyrus, or mammillary body, and between those of the amygdala and caudate nucleus, putamen, or globus pallidus which derived from the identical cerebra, were analyzed with Pearson's correlation. It was found that regarding the four elements of Ca, P, Mg, and Fe, a close relationship existed between the amygdala and hippocampus, globus pallidus, or mammillary body.

Mineral composition of and the relationships between them of human basal ganglia in very old age.

Trace elements and the relationships among them were investigated by direct chemical analysis in three basal ganglia regions in very old age individuals and age- and gender-related differences were assessed. After ordinary dissections at Nara Medical University were finished, the caudate nucleus, putamen, and globus pallidus belonging to the basal ganglia were removed from the identical cerebra of the subjects who consisted of 22 men and 23 women, ranging in age from 70 to 101 years (average age = 83.3 ± 7.5 years). After incineration with nitric acid and perchloric acid, the element contents were determined by inductively coupled plasma-atomic emission spectrometry. It was found that the Ca, P, and Mg contents increased significantly in the putamen with aging and the Mg content increased significantly in the globus pallidus with aging, but no elements increased significantly in the caudate nucleus with aging. Regarding the relationships among elements in the basal ganglia, extremely significant direct correlations were found among the Ca, P, and Mg contents in the putamen. These results suggested that slight calcification occurred in the putamen in very old age. With regard to seven elements of Ca, P, S, Mg, Zn, Fe, and Na, it was examined whether there were significant correlations among the caudate nucleus, putamen, and globus pallidus. It was found that there were extremely significant direct correlations among all of the three basal ganglia in the P content. Likewise, with regard to the Fe content, there were extremely or very significant direct correlations among all of the three basal ganglia. Regarding the gender difference in elements, it was found that the Ca content of the caudate nucleus was significantly higher in women than in men.

Gender differences in elements of human anterior commissure and olfactory bulb and tract.

To examine whether there were gender differences in the various brain regions, the authors investigated the gender differences in seven element contents of the anterior commissure, mammillary body, and olfactory bulb and tract by direct chemical analysis. After ordinary dissection at Nara Medical University was finished, the anterior commissures, mammillary bodies, and olfactory bulbs and tracts were resected from the cerebra cut at median line. The brain samples were treated with 99.5% ethanol three times to remove lipids. After ashing with nitric acid and perchloric acid, the seven element contents Ca, P, S, Mg, Zn, Fe, and Na were determined by inductively coupled plasma-atomic emission spectrometry. It was found that the Zn content was significantly higher in the anterior commissures of men than in those of women. In the olfactory bulbs and tracts, it was found that the Ca, P, and Zn contents were significantly higher in men than in women. In contrast, no significant difference was found between the mammillary bodies of men and women regarding the seven element contents.

Age-related changes of elements in human olfactory bulbs and tracts and relationships among their contents.

To elucidate compositional changes of the olfactory bulb and tract with aging, the authors investigated age-related changes of elements in the olfactory bulbs and tracts of Japanese and the relationships among the elements. After ordinary dissection at Nara Medical University was finished, the olfactory bulbs were resected with the olfactory tracts from 40 subjects. The subjects consisted of 15 men and 25 women, ranging in age from 65 to 102 years (average age = 84.6 +/- 7.5 years). After ashing with nitric acid and perchloric acid, element contents in the olfactory bulbs and tracts were analyzed by inductively coupled plasma-atomic emission spectrometry. Seven elements of Ca, P, S, Mg, Zn, Fe, and Na did not change significantly in the olfactory bulbs and tracts with aging. The Ca, P, and S contents of major elements were less than 10 mg/g in all of the olfactory bulbs and tracts. Regarding the relationships among the elements, extremely or very significant direct correlations were found among the contents of Ca, P, Mg, Zn, and Na in the olfactory bulbs and tracts, with one exception. In addition, an extremely significant direct correlation was found between S and Mg contents and a very significant direct correlation was found between P and S contents. As P increased in the olfactory bulb and tract, Ca, Mg, Zn, Na, and S also increased in the olfactory bulb and tract.