Alternative splicing in the variable domain of CaMKIIβ affects the level of F-actin association in developing neurons.

The Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII) β has an essential function in dendritic spines via binding to and reorganization of the actin cytoskeleton during plasticity events not shared by CaMKIIα isoform. CaMKIIβ and CaMKIIα isoforms have remarkable structural differences within the variable region. Three exons (E1, E3, and E4) are present in CaMKIIβ but not in CaMKIIα gene. Four splice variants of CaMKIIβ isoforms (CaMKIIβ, β\u27, βe and β\u27e) were discovered in embryonic and adult brains. Exons E1 (lacked in βe and β\u27e) and E4 (lacked in β\u27 and β\u27e) are subject to differential alternative splicing. We hypothesized that the sequences encoded by exons E1, E3, and/or E4 are involved in CaMKIIβ-specific bundling to the F-actin cytoskeleton. We tested the colocalization and association of these CaMKIIβ variants within an F-actin-rich structure (microspike) in CaMKIIα free embryonic day 18 (E-18) rat cortical neurons. Our results showed that CaMKIIβ and CaMKIIβ\u27 containing exon E1 displayed an association with F-actin, while CaMKIIβe and CaMKIIβ\u27e lacking E1 did not. Moreover, CaMKIIβ\u27 lacking exon E4 but having E1 showed decreased actin bindingcapacity compared to WT CaMKIIβ. This suggested E1 is required for the association between CaMKIIβ and F-actin, while E4 assists CaMKIIβ to associate with F-actin better. Thus, alternative splicing of CaMKIIβ variants in developing neurons may serve as a developmental switch for actin cytoskeleton-associated isoforms and therefore correlated with dendritic arborization and synapse formation during LTP

Preparation and evaluation of PEGylated phospholipid membrane coated layered double hydroxide nanoparticles

AbstractThe aim of the present study was to develop layered double hydroxide (LDH) nanoparticles coated with PEGylated phospholipid membrane. By comparing the size distribution and zeta potential, the weight ratio of LDH to lipid materials which constitute the outside membrane was identified as 2:1. Transmission electron microscopy photographs confirmed the core-shell structure of PEGylated phospholipid membrane coated LDH (PEG-PLDH) nanoparticles, and cell cytotoxicity assay showed their good cell viability on Hela and BALB/C-3T3 cells over the concentration range from 0.5 to 50 μg/mL

Physical and social environmental enrichment alleviate ferroptosis and inflammation with inhibition of TLR4/MyD88/p38MAPK pathway in chronic cerebral hypoperfusion rats

A typical enriched environment (EE), which combines physical activity and social interaction, has been proven to mitigate cognitive impairment caused by chronic cerebral hypoperfusion (CCH). However, it remains unclear how the different components of EE promote cognitive recovery after CCH. This study stripped out the different components of EE into physical environmental enrichment (PE) and social environmental enrichment (SE), and compared the neuroprotective effects of PE, SE and typical EE (PSE) in CCH. The results of novel object recognition and Morris water maze tests showed that PE, SE, and PSE improved cognitive function in CCH rats. Additionally, Nissl and TUNEL staining revealed that three EEs reduced neuronal loss in the hippocampus. PSE exhibited superior neuroprotective and functional improvement effects compared to PE and SE, while there was no significant difference between PE and SE. Furthermore, three EEs reduced lipid peroxidation in the hippocampus with decreasing the levels of MDA and increasing the activities of SOD and GSH. The expression of SLC7A11 and GPX4 was increased, while the level of p53 was reduced in three EEs. This suggested that three EEs inhibited ferroptosis by maintaining the redox homeostasis in the hippocampus. Three EEs reduced the levels of IL-β, TNF-α, and IL-6, thereby inhibiting neuroinflammation. Additionally, Western blotting and immunofluorescence results indicated that three EEs also inhibited the TLR4/MyD88/p38MAPK signaling pathway. These findings collectively demonstrated that the three EEs alleviated hippocampal ferroptosis and neuroinflammation in CCH rats, thereby reducing neuronal loss, which might be associated with the inhibition of the TLR4/MyD88/p38MAPK signaling pathway. Moreover, the study results supported that it is only through the combination of physical exercise and social interaction that the optimal neuroprotective effects can be achieved. These findings provided valuable insights for the prevention and treatment of vascular cognitive impairment

miR-142-3p suppresses apoptosis in spinal cord-injured rats

Spinal cord injury (SCI) leads to abnormal expression of miRs, leading to secondary responses such as oxidative stress, inflammation and apoptosis. In the present work, we screened the miRs involved and the associated pathway

Short-term effects of Kinesio taping combined with cervical muscles multi-angle isometric training in patients with cervical spondylosis

Abstract Objective The purpose of this study was to investigate the efficacy of Kinesio taping (KT) combined with multi-angle isometric resistance training for cervical spondylosis. Methods Sixty-one patients were divided into two groups by random number table method. Both groups were given multi-angle isometric training, the patients in the observation group were supplemented with Kinesio taping. Before and after treatment, the symptoms of cervical spine function were evaluated in two groups by visual analogue scale (VAS), cervical dysfunction index (NDI), cervical range of motion and muscle stiffness. Results After 3 weeks of treatment, VAS, NDI scores and the cervical range of motion were significantly better than before (P < 0.05). The range of anterior flexion and extension was significantly larger than the control group (P < 0.05), but the range of other motions were not certain. The muscle stiffness in KT group were significantly lower than the control group. Conclusion Kinesio taping combined with multi-angle isometric resistance training can further alleviate the clinical symptoms and correct the neck abnormal posture. But its effects on the range of cervical motion remain uncertain

Effect of Tetramethylpyrazine on Neuroplasticity after Transient Focal Cerebral Ischemia Reperfusion in Rats

Tetramethylpyrazine (TMP) has been widely used in ischemic stroke in China. The regulation of neuroplasticity may underlie the recovery of some neurological functions in ischemic stroke. Middle cerebral artery occlusion (MCAO) model was established in this study. Rats were divided into three groups: sham group, model group, and TMP group. The neurological function was evaluated using modified neurological severity score (mNSS). Following the neurological function test, expression of synaptophysin (SYP) and growth-associated protein 43 (GAP-43) were analyzed through immunohistochemistry at 3 d, 7 d, 14 d, and 28 d after MCAO. Finally, the synaptic structural plasticity was investigated using transmission electron microscopy (TEM). The TMP group showed better neurological function comparing to the model group. SYP levels increased gradually in ischemic penumbra (IP) in the model group and could be enhanced by TMP treatment at 7 d, 14 d, and 28 d, whereas GAP-43 levels increased from 3 d to 7 d and thereafter decreased gradually from 14 d to 28 d in the model group, which showed no significant improvement in the TMP group. The results of TEM showed a flatter synaptic interface, a thinner postsynaptic density (PSD), and a wider synaptic cleft in the model group, and the first two alterations could be ameliorated by TMP. Then, a Pearson’s correlation test revealed mNSS markedly correlated with SYP and synaptic ultrastructures. Taken together, TMP is capable of promoting functional outcome after ischemic stroke, and the mechanisms may be partially associated with regulation of neuroplasticity