Pub Date : 2024-08-01Epub Date: 2024-06-06DOI: 10.1007/s00221-024-06868-x
Juan Liu, Na Yang, Xiaomeng Wang, Wen Wang
Vascular dementia (VaD) is the most common cause of dementia in older adults. Due to the lack of effective treatment options, there is an urgent need to find an effective pharmaceutical compound to combat VaD. Piracetam has been reported to improve impaired cognitive function in a variety of conditions in both human and animal models. However, the role and mechanism of Piracetam in VaD remain unclear. Therefore this study aimed to elucidate the effect of Piracetam on a cellular model of VaD in vitro. We found that Piracetam enhanced the growth of OGD-stimulated SH-SY5Y cells. In addition, Piracetam inhibited the oxidative stress of OGD-stimulated SH-SY5Y cells. Further, Piracetam improved mitochondrial function of OGD-stimulated SH-SY5Y cells. Mechanistically, Piracetam inhibited the PI3K/Akt/mTOR pathway in OGD-stimulated SH-SY5Y cells. Collectively, Piracetam improved oxidative stress and mitochondrial dysfunction of OGD-stimulated SH-SY5Y cells through PI3K/Akt/mTOR axis. Hence, Piracetam has the potential to serve as a promising drug of VaD.
{"title":"Piracetam reduces oxidative stress and mitochondrial function impairment in an in vitro model of vascular dementia.","authors":"Juan Liu, Na Yang, Xiaomeng Wang, Wen Wang","doi":"10.1007/s00221-024-06868-x","DOIUrl":"10.1007/s00221-024-06868-x","url":null,"abstract":"<p><p>Vascular dementia (VaD) is the most common cause of dementia in older adults. Due to the lack of effective treatment options, there is an urgent need to find an effective pharmaceutical compound to combat VaD. Piracetam has been reported to improve impaired cognitive function in a variety of conditions in both human and animal models. However, the role and mechanism of Piracetam in VaD remain unclear. Therefore this study aimed to elucidate the effect of Piracetam on a cellular model of VaD in vitro. We found that Piracetam enhanced the growth of OGD-stimulated SH-SY5Y cells. In addition, Piracetam inhibited the oxidative stress of OGD-stimulated SH-SY5Y cells. Further, Piracetam improved mitochondrial function of OGD-stimulated SH-SY5Y cells. Mechanistically, Piracetam inhibited the PI3K/Akt/mTOR pathway in OGD-stimulated SH-SY5Y cells. Collectively, Piracetam improved oxidative stress and mitochondrial dysfunction of OGD-stimulated SH-SY5Y cells through PI3K/Akt/mTOR axis. Hence, Piracetam has the potential to serve as a promising drug of VaD.</p>","PeriodicalId":12268,"journal":{"name":"Experimental Brain Research","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rolling walkers are common walking aids for individuals with poor physical fitness or balance impairments. There is no doubt that rolling walkers are useful in assisting locomotion. On the other hand, it is arguable that walking with rolling walkers (WW) is effective for maintaining or restoring the nervous systems that are recruited during conventional walking (CW). This is because the differences and similarities of the neural control of these locomotion forms remain unknown. The purpose of the present study was to compare the neural control of WW and CW from the perspective of a split-belt adaptation paradigm and reveal how the adaptations that take place in WW and CW would affect each other. The anterior component of the ground reaction (braking) forces was measured during and after walking on a split-belt treadmill by 10 healthy subjects, and differences in the peak braking forces between the left and right sides were calculated as the index of the split-belt adaptation (the degree of asymmetry). The results demonstrated that (1) WW enabled subjects to respond to the split-belt condition immediately after its start as compared to CW; (2) the asymmetry movement pattern acquired by the split-belt adaptation in one gait mode (i.e., CW or WW) was less transferable to the other gait mode; (3) the asymmetry movement pattern acquired by the split-belt adaptation in CW was not completely washed out by subsequent execution in WW and vice versa. The results suggest unique control of WW and the specificity of neural control between WW and CW; use of the walkers is not necessarily appropriate as training for CW from the perspective of neural control.
{"title":"Distinct locomotor adaptation between conventional walking and walking with a walker.","authors":"Hiroki Obata, Tetsuya Ogawa, Naotsugu Kaneko, Keiichi Ishikawa, Kimitaka Nakazawa","doi":"10.1007/s00221-024-06863-2","DOIUrl":"10.1007/s00221-024-06863-2","url":null,"abstract":"<p><p>Rolling walkers are common walking aids for individuals with poor physical fitness or balance impairments. There is no doubt that rolling walkers are useful in assisting locomotion. On the other hand, it is arguable that walking with rolling walkers (WW) is effective for maintaining or restoring the nervous systems that are recruited during conventional walking (CW). This is because the differences and similarities of the neural control of these locomotion forms remain unknown. The purpose of the present study was to compare the neural control of WW and CW from the perspective of a split-belt adaptation paradigm and reveal how the adaptations that take place in WW and CW would affect each other. The anterior component of the ground reaction (braking) forces was measured during and after walking on a split-belt treadmill by 10 healthy subjects, and differences in the peak braking forces between the left and right sides were calculated as the index of the split-belt adaptation (the degree of asymmetry). The results demonstrated that (1) WW enabled subjects to respond to the split-belt condition immediately after its start as compared to CW; (2) the asymmetry movement pattern acquired by the split-belt adaptation in one gait mode (i.e., CW or WW) was less transferable to the other gait mode; (3) the asymmetry movement pattern acquired by the split-belt adaptation in CW was not completely washed out by subsequent execution in WW and vice versa. The results suggest unique control of WW and the specificity of neural control between WW and CW; use of the walkers is not necessarily appropriate as training for CW from the perspective of neural control.</p>","PeriodicalId":12268,"journal":{"name":"Experimental Brain Research","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-06-25DOI: 10.1007/s00221-024-06878-9
Sajjad Daneshgar, Taylor Tvrdy, Roger M Enoka
The purpose was to identify the variables that can explain the variance in the grooved pegboard times of older adults categorized as either fast or slow performers. Participants (n = 28; 60-83 years) completed two experimental sessions, before and after 6 practice sessions of the grooved pegboard test. The 2 groups were identified based on average pegboard times during the practice sessions. Average pegboard time during practice was 73 ± 11 s for the fast group and 85 ± 13 s for the slow group. Explanatory variables for the pegboard times before and after practice were the durations of 4 peg-manipulation phases and 12 measures of force steadiness (coefficient of variation [CV] for force) during isometric contractions with the index finger abductor and wrist extensor muscles. Time to complete the grooved pegboard test after practice decreased by 25 ± 11% for the fast group and by 28 ± 10% for the slow group. Multiple regression models explained more of the variance in the pegboard times for the fast group before practice (Adjusted R2 = 0.85) than after practice (R2 = 0.51), whereas the variance explained for the slow group was similar before (Adjusted R2 = 0.67) and after (Adjusted R2 = 0.64) practice. The explanatory variables differed between before and after practice for the fast group but only slightly for the slow group. These findings indicate that performance-based stratification of older adults can identify unique adjustments in motor function that are independent of chronological age.
{"title":"Explaining the influence of practice on the grooved pegboard times of older adults: role of force steadiness.","authors":"Sajjad Daneshgar, Taylor Tvrdy, Roger M Enoka","doi":"10.1007/s00221-024-06878-9","DOIUrl":"10.1007/s00221-024-06878-9","url":null,"abstract":"<p><p>The purpose was to identify the variables that can explain the variance in the grooved pegboard times of older adults categorized as either fast or slow performers. Participants (n = 28; 60-83 years) completed two experimental sessions, before and after 6 practice sessions of the grooved pegboard test. The 2 groups were identified based on average pegboard times during the practice sessions. Average pegboard time during practice was 73 ± 11 s for the fast group and 85 ± 13 s for the slow group. Explanatory variables for the pegboard times before and after practice were the durations of 4 peg-manipulation phases and 12 measures of force steadiness (coefficient of variation [CV] for force) during isometric contractions with the index finger abductor and wrist extensor muscles. Time to complete the grooved pegboard test after practice decreased by 25 ± 11% for the fast group and by 28 ± 10% for the slow group. Multiple regression models explained more of the variance in the pegboard times for the fast group before practice (Adjusted R<sup>2</sup> = 0.85) than after practice (R<sup>2</sup> = 0.51), whereas the variance explained for the slow group was similar before (Adjusted R<sup>2</sup> = 0.67) and after (Adjusted R<sup>2</sup> = 0.64) practice. The explanatory variables differed between before and after practice for the fast group but only slightly for the slow group. These findings indicate that performance-based stratification of older adults can identify unique adjustments in motor function that are independent of chronological age.</p>","PeriodicalId":12268,"journal":{"name":"Experimental Brain Research","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141445923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-07-02DOI: 10.1007/s00221-024-06880-1
Cindy Jagorska, Martin Riemer
The influence of travel time on perceived traveled distance has often been studied, but the results are inconsistent regarding the relationship between the two magnitudes. We argue that this is due to differences in the lengths of investigated travel distances and hypothesize that the influence of travel time differs for rather short compared to rather long traveled distances. We tested this hypothesis in a virtual environment presented on a desktop as well as through a head-mounted display. Our results show that, for longer distances, more travel time leads to longer perceived distance, while we do not find an influence of travel time on shorter distances. The presentation through an HMD vs. desktop only influenced distance judgments in the short distance condition. These results are in line with the idea that the influence of travel time varies by the length of the traveled distance, and provide insights on the question of how distance perception in path integration studies is affected by travel time, thereby resolving inconsistencies reported in previous studies.
{"title":"The influence of travel time on perceived traveled distance varies by spatiotemporal scale.","authors":"Cindy Jagorska, Martin Riemer","doi":"10.1007/s00221-024-06880-1","DOIUrl":"10.1007/s00221-024-06880-1","url":null,"abstract":"<p><p>The influence of travel time on perceived traveled distance has often been studied, but the results are inconsistent regarding the relationship between the two magnitudes. We argue that this is due to differences in the lengths of investigated travel distances and hypothesize that the influence of travel time differs for rather short compared to rather long traveled distances. We tested this hypothesis in a virtual environment presented on a desktop as well as through a head-mounted display. Our results show that, for longer distances, more travel time leads to longer perceived distance, while we do not find an influence of travel time on shorter distances. The presentation through an HMD vs. desktop only influenced distance judgments in the short distance condition. These results are in line with the idea that the influence of travel time varies by the length of the traveled distance, and provide insights on the question of how distance perception in path integration studies is affected by travel time, thereby resolving inconsistencies reported in previous studies.</p>","PeriodicalId":12268,"journal":{"name":"Experimental Brain Research","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-06-12DOI: 10.1007/s00221-024-06869-w
Caíque Olegário Diniz E Magalhães, Ricardo Augusto Leoni De Sousa, Bruno Ferreira Mendes, Isabela Rocha Dias, Ramona Ramalho Souza Pereira, Gabriela Cruz Pereira, Kil Sun Lee, Marco Fabricio Dias Peixoto, Ricardo Cardoso Cassilhas
This study aimed to compare the effects of High-Intensity Interval Training (HIIT) performed in a single session(1xHIIT) versus three daily sessions (3xHIIT) on fitness level and behavior of aged rats. Eighteen-month-old Wistar rats were assigned to Untrained (UN), 1xHIIT, or 3xHIIT (n = 12/group). Both groups, 1xHIIT and 3xHIIT, performed 15 min of a treadmill running HIIT protocol during 8 weeks. 1xHIIT protocol consisted of a single daily session of 15 min, while the 3xHIIT performed three daily sessions of 5 min with a 4 h interval between the sessions. Morris Water Maze (MWM) task was used to evaluate spatial learning and memory. Splash test, Forced Swim test, and Elevated Plus Maze task (EPM) were used to evaluate anhedonic, depressive-like, and anxious behaviors, respectively. Rats were euthanized, and the hippocampus was harvested for western blot analyses (CaMKII and BDNF). Both HIIT protocols improved VO2max and spatial memory. Notably, only the 3xHIIT protocol attenuated anxious and depressive-like behaviors. Western blot analyses of the hippocampus revealed that both HIIT protocols increased BDNF levels. BDNF levels were higher in the 3xHIIT when compared with 1xHIIT group, and we observed increasement of the CamKII levels just in the 3x HIIT group. Therefore, this study provides evidence indicating that accumulated HIIT sessions is more effective than traditional daily HIIT sessions in improving fitness level, cognitive function, memory, inhibiting the development of mood disorders, and enhancing BDNF and CaMKII levels in the hippocampus of aged rats.
{"title":"Accumulated HIIT inhibits anxiety and depression, improves cognitive function, and memory-related proteins in the hippocampus of aged rats.","authors":"Caíque Olegário Diniz E Magalhães, Ricardo Augusto Leoni De Sousa, Bruno Ferreira Mendes, Isabela Rocha Dias, Ramona Ramalho Souza Pereira, Gabriela Cruz Pereira, Kil Sun Lee, Marco Fabricio Dias Peixoto, Ricardo Cardoso Cassilhas","doi":"10.1007/s00221-024-06869-w","DOIUrl":"10.1007/s00221-024-06869-w","url":null,"abstract":"<p><p>This study aimed to compare the effects of High-Intensity Interval Training (HIIT) performed in a single session(1xHIIT) versus three daily sessions (3xHIIT) on fitness level and behavior of aged rats. Eighteen-month-old Wistar rats were assigned to Untrained (UN), 1xHIIT, or 3xHIIT (n = 12/group). Both groups, 1xHIIT and 3xHIIT, performed 15 min of a treadmill running HIIT protocol during 8 weeks. 1xHIIT protocol consisted of a single daily session of 15 min, while the 3xHIIT performed three daily sessions of 5 min with a 4 h interval between the sessions. Morris Water Maze (MWM) task was used to evaluate spatial learning and memory. Splash test, Forced Swim test, and Elevated Plus Maze task (EPM) were used to evaluate anhedonic, depressive-like, and anxious behaviors, respectively. Rats were euthanized, and the hippocampus was harvested for western blot analyses (CaMKII and BDNF). Both HIIT protocols improved VO<sub>2</sub>max and spatial memory. Notably, only the 3xHIIT protocol attenuated anxious and depressive-like behaviors. Western blot analyses of the hippocampus revealed that both HIIT protocols increased BDNF levels. BDNF levels were higher in the 3xHIIT when compared with 1xHIIT group, and we observed increasement of the CamKII levels just in the 3x HIIT group. Therefore, this study provides evidence indicating that accumulated HIIT sessions is more effective than traditional daily HIIT sessions in improving fitness level, cognitive function, memory, inhibiting the development of mood disorders, and enhancing BDNF and CaMKII levels in the hippocampus of aged rats.</p>","PeriodicalId":12268,"journal":{"name":"Experimental Brain Research","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-07-03DOI: 10.1007/s00221-024-06885-w
Aman Bedi, Paul N Russell, William S Helton
Researchers dispute the cause of errors in high Go, low No Go target detection tasks, like the Sustained Attention to Response Task (SART). Some researchers propose errors in the SART are due to perceptual decoupling, where a participant is unaware of stimulus identity. This lack of external awareness causes an erroneous response. Other researchers suggest the majority of the errors in the SART are instead due to response leniency, not perceptual decoupling. Response delays may enable a participant who is initially unaware of stimulus identity, perceptually decoupled, to become aware of stimulus identity, or perceptually recoupled. If, however, the stimulus presentation time is shortened to the minimum necessary for stimulus recognition and the stimulus is disrupted with a structured mask, then there should be no time to enable perception to recouple even with a response delay. From the perceptual decoupling perspective, there should be no impact of a response delay on performance in this case. Alternatively if response bias is critical, then even in this case a response delay may impact performance. In this study, we shortened stimulus presentation time and added a structured mask. We examined whether a response delay impacted performance in the SART and tasks where the SART's response format was reversed. We expected a response delay would only impact signal detection theory bias, c, in the SART, where response leniency is an issue. In the reverse formatted SART, since bias was not expected to be lenient, we expected no impact or minimal impact of a response delay on response bias. These predictions were verified. Response bias is more critical in understanding SART performance, than perceptual decoupling, which is rare if it occurs at all in the SART.
研究人员对高 Go 低 No Go 目标检测任务(如持续注意反应任务 (SART))中出现错误的原因存在争议。一些研究人员认为,SART 中的错误是由于知觉脱钩造成的,即受试者没有意识到刺激物的身份。这种外部意识的缺乏导致了错误的反应。其他研究人员则认为,SART 中的大部分错误是由于反应宽松造成的,而非知觉脱钩。反应延迟可能会使最初没有意识到刺激特征、知觉脱钩的被试意识到刺激特征或知觉再脱钩。但是,如果刺激呈现时间被缩短到识别刺激所需的最短时间,并且刺激被结构化掩码干扰,那么即使有反应延迟,也不应该有时间让知觉重新耦合。从知觉解耦的角度来看,在这种情况下,反应延迟对成绩应该没有影响。相反,如果反应偏差至关重要,那么即使在这种情况下,反应延迟也可能会影响成绩。在本研究中,我们缩短了刺激呈现时间,并添加了一个结构化掩码。我们考察了反应延迟是否会影响 SART 和 SART 反应形式相反的任务的成绩。我们预计反应延迟只会影响 SART 中的信号检测理论偏差 c,因为在 SART 中,反应宽松度是一个问题。而在反向格式的 SART 中,由于不存在宽松的偏差,我们预计反应延迟对反应偏差不会产生影响或影响极小。这些预测都得到了验证。与知觉脱钩相比,响应偏差对于理解 SART 的性能更为关键,而知觉脱钩即使在 SART 中出现,也是非常罕见的。
{"title":"Perceptual decoupling in the sustained attention to response task is unlikely.","authors":"Aman Bedi, Paul N Russell, William S Helton","doi":"10.1007/s00221-024-06885-w","DOIUrl":"10.1007/s00221-024-06885-w","url":null,"abstract":"<p><p>Researchers dispute the cause of errors in high Go, low No Go target detection tasks, like the Sustained Attention to Response Task (SART). Some researchers propose errors in the SART are due to perceptual decoupling, where a participant is unaware of stimulus identity. This lack of external awareness causes an erroneous response. Other researchers suggest the majority of the errors in the SART are instead due to response leniency, not perceptual decoupling. Response delays may enable a participant who is initially unaware of stimulus identity, perceptually decoupled, to become aware of stimulus identity, or perceptually recoupled. If, however, the stimulus presentation time is shortened to the minimum necessary for stimulus recognition and the stimulus is disrupted with a structured mask, then there should be no time to enable perception to recouple even with a response delay. From the perceptual decoupling perspective, there should be no impact of a response delay on performance in this case. Alternatively if response bias is critical, then even in this case a response delay may impact performance. In this study, we shortened stimulus presentation time and added a structured mask. We examined whether a response delay impacted performance in the SART and tasks where the SART's response format was reversed. We expected a response delay would only impact signal detection theory bias, c, in the SART, where response leniency is an issue. In the reverse formatted SART, since bias was not expected to be lenient, we expected no impact or minimal impact of a response delay on response bias. These predictions were verified. Response bias is more critical in understanding SART performance, than perceptual decoupling, which is rare if it occurs at all in the SART.</p>","PeriodicalId":12268,"journal":{"name":"Experimental Brain Research","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-06-19DOI: 10.1007/s00221-024-06875-y
Lv Dingyi, Hu Libin, Piao Jifeng, Zhiquan Ding, Li Yulong, Wu Zhangyi, Yin Yunong, Wang Qinghua, Li Feng
Neuroinflammation and microglia polarization play pivotal roles in brain injury induced by intracerebral hemorrhage (ICH). Despite the well-established involvement of CXC motif chemokine ligand 16 (CXCL16) in regulating inflammatory responses across various diseases, its specific functions in the context of neuroinflammation and microglial polarization following ICH remain elusive. In this study, we investigated the impact of CXCL16 on neuroinflammation and microglia polarization using both mouse and cell models. Our findings revealed elevated CXCL16 expression in mice following ICH and in BV2 cells after lipopolysaccharide (LPS) stimulation. Specific silencing of CXCL16 using siRNA led to a reduction in the expression of neuroinflammatory factors, including IL-1β and IL-6, as well as decreased expression of the M1 microglia marker iNOS. Simultaneously, it enhanced the expression of anti-inflammatory factors such as IL-10 and the M2 microglia marker Arg-1. These results were consistent across both mouse and cell models. Intriguingly, co-administration of the PI3K-specific agonist 740 Y-P with siRNA in LPS-stimulated cells reversed the effects of siRNA. In conclusion, silencing CXCL16 can positively alleviate neuroinflammation and M1 microglial polarization in BV2 inflammation models and ICH mice. Furthermore, in BV2 cells, this beneficial effect is mediated through the PI3K/Akt pathway. Inhibition of CXCL16 could be a novel approach for treating and diagnosing cerebral hemorrhage.
{"title":"Silencing CXCL16 alleviate neuroinflammation and M1 microglial polarization in mouse brain hemorrhage model and BV2 cell model through PI3K/AKT pathway.","authors":"Lv Dingyi, Hu Libin, Piao Jifeng, Zhiquan Ding, Li Yulong, Wu Zhangyi, Yin Yunong, Wang Qinghua, Li Feng","doi":"10.1007/s00221-024-06875-y","DOIUrl":"10.1007/s00221-024-06875-y","url":null,"abstract":"<p><p>Neuroinflammation and microglia polarization play pivotal roles in brain injury induced by intracerebral hemorrhage (ICH). Despite the well-established involvement of CXC motif chemokine ligand 16 (CXCL16) in regulating inflammatory responses across various diseases, its specific functions in the context of neuroinflammation and microglial polarization following ICH remain elusive. In this study, we investigated the impact of CXCL16 on neuroinflammation and microglia polarization using both mouse and cell models. Our findings revealed elevated CXCL16 expression in mice following ICH and in BV2 cells after lipopolysaccharide (LPS) stimulation. Specific silencing of CXCL16 using siRNA led to a reduction in the expression of neuroinflammatory factors, including IL-1β and IL-6, as well as decreased expression of the M1 microglia marker iNOS. Simultaneously, it enhanced the expression of anti-inflammatory factors such as IL-10 and the M2 microglia marker Arg-1. These results were consistent across both mouse and cell models. Intriguingly, co-administration of the PI3K-specific agonist 740 Y-P with siRNA in LPS-stimulated cells reversed the effects of siRNA. In conclusion, silencing CXCL16 can positively alleviate neuroinflammation and M1 microglial polarization in BV2 inflammation models and ICH mice. Furthermore, in BV2 cells, this beneficial effect is mediated through the PI3K/Akt pathway. Inhibition of CXCL16 could be a novel approach for treating and diagnosing cerebral hemorrhage.</p>","PeriodicalId":12268,"journal":{"name":"Experimental Brain Research","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The aim of this study was to investigate histone deacetylase 6 (HDAC6) modifies the heat shock protein 90 (HSP90) and heat shock transcription factor 1 (HSF1) affect the levels of pathological markers such as Aβ oligomers (Aβo) and Tau phosphorylation (p-Tau) in APP/PS1 double transgenic mice hippocampal tissues or HT22 neurons as well as the changes in cognitive behavioral functions of mice. (1) APP/PS1 transgenic mice (6 months old, 25 ~ 30 g) were randomly assigned to 5 experimental groups, C57BL/6J mice (6 months old, 25 ~ 30 g) were used as 4 control groups, with 8 mice in each group. All mice underwent intracerebroventricular (i.c.v.) cannulation, and the experimental groups were administered with normal saline (APP + NS group), HDAC6 agonist tubastatin A hydrochloride (TSA) (APP + TSA group) or HDAC6 agonist theophylline (Theo) (APP + Theo group), HSP90 inhibitor Ganetespib (Gane) (APP + Gane group), or a combination of pre-injected Gane by TSA (APP + Gane + TSA group); the control group received i.c.v. injections of Gane (Gane group), TSA (TSA group), Theo (Theo group) or NS (NS group), respectively. (2) Mouse hippocampal neurons HT22 were randomly divided into a control group (Control) and an Aβ1-42 intervention group (Aβ). Within the Aβ group, further divisions were made for knockdown HSP90 (Aβ + siHSP90 group), overexpression HSP90 (Aβ + OE-HSP90 group), knockdown HSF1(Aβ + siHSF1 group) and knockdown HSF1 followed by overexpression HSP90 (Aβ + siHSF1 + OE-HSP90 group), resulting in a total of 6 groups. Morris water maze test was used to evaluate the cognitive behavior of the mice. Western blot and immunohistochemistry or immunofluorescence were performed to detect the levels of HDAC6, HSP90, HSF1, Aβ1-42, Tau protein, and p-Tau in the hippocampal tissue or HT22 cells. qRT-PCR was used to measure the levels of hdac6, hsp90, and hsf1 mRNA in the hippocampus or nerve cells. (1) The levels of HDAC6, Aβ1-42 and p-Tau were elevated, while HSP90 and HSF1 were decreased in the hippocampal tissue of APP/PS1 transgenic mice (all P < 0.01). Inhibiting HDAC6 upregulated the expressions of HSP90 and HSF1 in the hippocampal tissue of APP/PS1 mice, while decreasing the levels of Aβ1-42 and p-Tau as well as improving the spatial cognitive behavior in mice (P < 0.05 or P < 0.01). The opposite effects were observed upon HDAC6 activation. However, inhibiting HSP90 reduced the expression of HSF1 (P < 0.01) and increased the levels of Aβ1-42 and p-Tau (P < 0.05 or P < 0.01) but did not significantly affect the expression of HDAC6 (P > 0.05). No significant changes were observed in the aforementioned indicators in the 4 control groups (P > 0.05). (2) In the Aβ1-42 intervention group, HDAC6 and Aβ1-42, p-Tau expression levels were elevated, while HSP90 and HSF1 expressions were all decreased, and cell viability was reduced (P < 0.05 or P < 0.01). Overexpression of HSP90 upreg
{"title":"HDAC6 modulates the cognitive behavioral function and hippocampal tissue pathological changes of APP/PS1 transgenic mice through HSP90-HSF1 pathway.","authors":"Bingyi Wang, Siyu Liu, Kaimin Hao, YaruWang Wang, Zongjing Li, Yuanyuan Lou, Yuan Chang, Wenxiu Qi","doi":"10.1007/s00221-024-06858-z","DOIUrl":"10.1007/s00221-024-06858-z","url":null,"abstract":"<p><p>The aim of this study was to investigate histone deacetylase 6 (HDAC6) modifies the heat shock protein 90 (HSP90) and heat shock transcription factor 1 (HSF1) affect the levels of pathological markers such as Aβ oligomers (Aβo) and Tau phosphorylation (p-Tau) in APP/PS1 double transgenic mice hippocampal tissues or HT22 neurons as well as the changes in cognitive behavioral functions of mice. (1) APP/PS1 transgenic mice (6 months old, 25 ~ 30 g) were randomly assigned to 5 experimental groups, C57BL/6J mice (6 months old, 25 ~ 30 g) were used as 4 control groups, with 8 mice in each group. All mice underwent intracerebroventricular (i.c.v.) cannulation, and the experimental groups were administered with normal saline (APP + NS group), HDAC6 agonist tubastatin A hydrochloride (TSA) (APP + TSA group) or HDAC6 agonist theophylline (Theo) (APP + Theo group), HSP90 inhibitor Ganetespib (Gane) (APP + Gane group), or a combination of pre-injected Gane by TSA (APP + Gane + TSA group); the control group received i.c.v. injections of Gane (Gane group), TSA (TSA group), Theo (Theo group) or NS (NS group), respectively. (2) Mouse hippocampal neurons HT22 were randomly divided into a control group (Control) and an Aβ<sub>1-42</sub> intervention group (Aβ). Within the Aβ group, further divisions were made for knockdown HSP90 (Aβ + siHSP90 group), overexpression HSP90 (Aβ + OE-HSP90 group), knockdown HSF1(Aβ + siHSF1 group) and knockdown HSF1 followed by overexpression HSP90 (Aβ + siHSF1 + OE-HSP90 group), resulting in a total of 6 groups. Morris water maze test was used to evaluate the cognitive behavior of the mice. Western blot and immunohistochemistry or immunofluorescence were performed to detect the levels of HDAC6, HSP90, HSF1, Aβ<sub>1-42</sub>, Tau protein, and p-Tau in the hippocampal tissue or HT22 cells. qRT-PCR was used to measure the levels of hdac6, hsp90, and hsf1 mRNA in the hippocampus or nerve cells. (1) The levels of HDAC6, Aβ<sub>1-42</sub> and p-Tau were elevated, while HSP90 and HSF1 were decreased in the hippocampal tissue of APP/PS1 transgenic mice (all P < 0.01). Inhibiting HDAC6 upregulated the expressions of HSP90 and HSF1 in the hippocampal tissue of APP/PS1 mice, while decreasing the levels of Aβ<sub>1-42</sub> and p-Tau as well as improving the spatial cognitive behavior in mice (P < 0.05 or P < 0.01). The opposite effects were observed upon HDAC6 activation. However, inhibiting HSP90 reduced the expression of HSF1 (P < 0.01) and increased the levels of Aβ<sub>1-42</sub> and p-Tau (P < 0.05 or P < 0.01) but did not significantly affect the expression of HDAC6 (P > 0.05). No significant changes were observed in the aforementioned indicators in the 4 control groups (P > 0.05). (2) In the Aβ<sub>1-42</sub> intervention group, HDAC6 and Aβ<sub>1-42</sub>, p-Tau expression levels were elevated, while HSP90 and HSF1 expressions were all decreased, and cell viability was reduced (P < 0.05 or P < 0.01). Overexpression of HSP90 upreg","PeriodicalId":12268,"journal":{"name":"Experimental Brain Research","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-06-19DOI: 10.1007/s00221-024-06873-0
Adam Grinberg, Andrew Strong, Johan Strandberg, Jonas Selling, Dario G Liebermann, Martin Björklund, Charlotte K Häger
Musculoskeletal trauma often leads to lasting psychological impacts stemming from concerns of future injuries. Often referred to as kinesiophobia or re-injury anxiety, such concerns have been shown to hinder return to physical activity and are believed to increase the risk for secondary injuries. Screening for re-injury anxiety is currently restricted to subjective questionnaires, which are prone to self-report bias. We introduce a novel approach to objectively identify electrocortical activity associated with the threat of destabilising perturbations. We aimed to explore its feasibility among non-injured persons, with potential future implementation for screening of re-injury anxiety. Twenty-three participants stood blindfolded on a translational balance perturbation platform. Consecutive auditory stimuli were provided as low (neutral stimulus [CS-]) or high (conditioned stimulus [CS+]) tones. For the main experimental protocol (Protocol I), half of the high tones were followed by a perturbation in one of eight unpredictable directions. A separate validation protocol (Protocol II) requiring voluntary squatting without perturbations was performed with 12 participants. Event-related potentials (ERP) were computed from electroencephalography recordings and significant time-domain components were detected using an interval-wise testing procedure. High-amplitude early contingent negative variation (CNV) waves were significantly greater for CS+ compared with CS- trials in all channels for Protocol I (> 521-800ms), most prominently over frontal and central midline locations (P ≤ 0.001). For Protocol II, shorter frontal ERP components were observed (541-609ms). Our test paradigm revealed electrocortical activation possibly associated with movement-related fear. Exploring the discriminative validity of the paradigm among individuals with and without self-reported re-injury anxiety is warranted.
{"title":"Electrocortical activity associated with movement-related fear: a methodological exploration of a threat-conditioning paradigm involving destabilising perturbations during quiet standing.","authors":"Adam Grinberg, Andrew Strong, Johan Strandberg, Jonas Selling, Dario G Liebermann, Martin Björklund, Charlotte K Häger","doi":"10.1007/s00221-024-06873-0","DOIUrl":"10.1007/s00221-024-06873-0","url":null,"abstract":"<p><p>Musculoskeletal trauma often leads to lasting psychological impacts stemming from concerns of future injuries. Often referred to as kinesiophobia or re-injury anxiety, such concerns have been shown to hinder return to physical activity and are believed to increase the risk for secondary injuries. Screening for re-injury anxiety is currently restricted to subjective questionnaires, which are prone to self-report bias. We introduce a novel approach to objectively identify electrocortical activity associated with the threat of destabilising perturbations. We aimed to explore its feasibility among non-injured persons, with potential future implementation for screening of re-injury anxiety. Twenty-three participants stood blindfolded on a translational balance perturbation platform. Consecutive auditory stimuli were provided as low (neutral stimulus [CS<sup>-</sup>]) or high (conditioned stimulus [CS<sup>+</sup>]) tones. For the main experimental protocol (Protocol I), half of the high tones were followed by a perturbation in one of eight unpredictable directions. A separate validation protocol (Protocol II) requiring voluntary squatting without perturbations was performed with 12 participants. Event-related potentials (ERP) were computed from electroencephalography recordings and significant time-domain components were detected using an interval-wise testing procedure. High-amplitude early contingent negative variation (CNV) waves were significantly greater for CS<sup>+</sup> compared with CS<sup>-</sup> trials in all channels for Protocol I (> 521-800ms), most prominently over frontal and central midline locations (P ≤ 0.001). For Protocol II, shorter frontal ERP components were observed (541-609ms). Our test paradigm revealed electrocortical activation possibly associated with movement-related fear. Exploring the discriminative validity of the paradigm among individuals with and without self-reported re-injury anxiety is warranted.</p>","PeriodicalId":12268,"journal":{"name":"Experimental Brain Research","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Recent studies on the imitation of intransitive gestures suggest that the body part effect relies mainly upon the direct route of the dual-route model through a visuo-transformation mechanism. Here, we test the visuo-constructive hypothesis which posits that the visual complexity may directly potentiate the body part effect for meaningless gestures. We predicted that the difference between imitation of hand and finger gestures would increase with the visuo-spatial complexity of gestures. Second, we aimed to identify some of the visuo-spatial predictors of meaningless finger imitation skills. Thirty-eight participants underwent an imitation task containing three distinct set of gestures, that is, meaningful gestures, meaningless gestures with low visual complexity, and meaningless gestures with higher visual complexity than the first set of meaningless gestures. Our results were in general agreement with the visuo-constructive hypothesis, showing an increase in the difference between hand and finger gestures, but only for meaningless gestures with higher visuo-spatial complexity. Regression analyses confirm that imitation accuracy decreases with resource-demanding visuo-spatial factors. Taken together, our results suggest that the body part effect is highly dependent on the visuo-spatial characteristics of the gestures.
{"title":"Visuo-spatial complexity potentiates the body-part effect in intransitive imitation of meaningless gestures.","authors":"Mathieu Lesourd, Josselin Baumard, Maximilien Metaireau, Laurence Picard","doi":"10.1007/s00221-024-06865-0","DOIUrl":"10.1007/s00221-024-06865-0","url":null,"abstract":"<p><p>Recent studies on the imitation of intransitive gestures suggest that the body part effect relies mainly upon the direct route of the dual-route model through a visuo-transformation mechanism. Here, we test the visuo-constructive hypothesis which posits that the visual complexity may directly potentiate the body part effect for meaningless gestures. We predicted that the difference between imitation of hand and finger gestures would increase with the visuo-spatial complexity of gestures. Second, we aimed to identify some of the visuo-spatial predictors of meaningless finger imitation skills. Thirty-eight participants underwent an imitation task containing three distinct set of gestures, that is, meaningful gestures, meaningless gestures with low visual complexity, and meaningless gestures with higher visual complexity than the first set of meaningless gestures. Our results were in general agreement with the visuo-constructive hypothesis, showing an increase in the difference between hand and finger gestures, but only for meaningless gestures with higher visuo-spatial complexity. Regression analyses confirm that imitation accuracy decreases with resource-demanding visuo-spatial factors. Taken together, our results suggest that the body part effect is highly dependent on the visuo-spatial characteristics of the gestures.</p>","PeriodicalId":12268,"journal":{"name":"Experimental Brain Research","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}