Neuroscience
-
Maintaining standing balance involves multisensory processing and integration to produce dynamic motor responses. Electrical vestibular stimulation (EVS) delivered over the mastoid processes can be used to explore the vestibular control of balance. The purpose of this study was to determine whether intrinsic foot muscles exhibit vestibular-evoked balance responses and to characterize the traits associated with these responses. ⋯ When vision was occluded, the EVS-EMG and EVS-AP forces coherence function amplitude increased at low frequencies (<2 Hz) and was accompanied by a heightened medium-latency peak amplitude for all muscles as well as the whole-body balance response (AP forces) compared to when static visual cues were present. The enhanced coherence amplitudes at lower frequencies may highlight a mechanism for the increase in postural sway from vision to occluded vision. The current findings indicate that the vestibular control of standing balance can be represented by the intrinsic foot muscles and implicate a postural role for these muscles in modulating quiet standing.
-
Epigenetic modulation participates in the mechanism of multiple types of pathological pain, so targeting the involved regulators may be a promising strategy for pain treatment. Our previous research identified the analgesic effect of the histone deacetylase (HDAC) inhibitor trichostatin A (TSA) on mechanical hyperalgesia in a rat model of bone cancer pain (BCP) via restoration of μ-opioid receptor (MOR) expression. However, the specific types of HDACs contributing to BCP have not been explored. ⋯ Notably, HDAC2 knock-down did not restore MOR expression, but it robustly reversed the down-regulation of potassium-chloride cotransporter 2 (KCC2). The impaired KCC2 expression is a vital mechanism of many types of pathological pain. Therefore, our results demonstrated that HDAC2 in spinal cord contributed to the mechanical hyperalgesia in BCP rats, and this effect may be associated with KCC2 modulation.
-
Steroids have been demonstrated to play profound roles in the regulation of hippocampal function by acting on their receptors, which need coactivators for their transcriptional activities. Previous studies have shown that steroid receptor coactivator-1 (SRC-1) is the predominant coactivator in the hippocampus, but its exact role and the underlying mechanisms remain unclear. In this study, we constructed SRC-1 RNA interference (RNAi) lentiviruses, injected them into the hippocampus of male mice, and then examined the changes in the expression of selected synaptic proteins, CA1 synapse density, postsynaptic density (PSD) thickness, and in vivo long-term potentiation (LTP). ⋯ The in vivo results showed that SRC-1 knockdown significantly decreased the expression of synaptic proteins and CA1 synapse density as well as PSD thickness; SRC-1 knockdown also significantly impaired in vivo LTP and disrupted spatial learning and memory. The in vitro results showed that while the expression of synaptic proteins was significantly decreased by SRC-1 knockdown, pCREB expression was also significantly decreased. The above results suggest a pivotal role of SRC-1 in the regulation of hippocampal synaptic plasticity and spatial learning and memory, strongly indicating SRC-1 may serve as a novel therapeutic target for hippocampus-dependent memory disorders.
-
Both chemical and physical microenvironments appear to be important for lineage specification of umbilical cord mesenchymal stem cells (UCMSCs). However, physical factors such as the elastic modulus in traumatic brain injury (TBI) are seldom studied. Intracranial hypertension and cerebral edema after TBI may change the brain's physical microenvironment, which inhibits neural lineage specification of transplanted UCMSCs. ⋯ The results showed that mild hypothermia significantly reduced intracranial pressure and brain water content, indicating modulation of the elastic modulus by mild hypothermia. An examination with atomic force microscopy (AFM) in a cell injury model in vitro further verified hypothermia-regulated elastic modulus. In this study, we found a novel role of mild hypothermia in modulating the elastic modulus of the injured brain, resulting in the promotion of neural lineage specification of UCMSCs, which suggested that the combination of mild hypothermia had more advantages in cell-based therapy after TBI.
-
Recently, it has been shown that serotonin 5-HT1A receptor interacts with dopamine D2 receptor in vitro. However, the existence of 5-HT1A-D2 heteromers in native tissue remains unexplored. In the present study, we investigated 5-HT1A-D2 receptor heteromerization in mice treated acutely or chronically with paroxetine (10 mg/kg) or risperidone (0.05 mg/kg). ⋯ These changes were not accompanied by any changes in the expression of mRNAs (measured by in situ hybridization) or densities of 5-HT1A and D2 receptors (quantified by receptor autoradiography with [3H]8-OH-DPAT and [3H]domperidone, respectively), what all indicated that paroxetine and risperidone facilitated 5-HT1A-D2 heteromer formation independently of the receptor expression. In vitro homogenous time-resolved FRET (HTRF) study confirmed the ability of tested drugs to influence the human 5-HT1A-D2 heteromer formation. The obtained data indicate that the increase in 5-HT1A-D2 receptor heteromerization is a common molecular characteristic of paroxetine and low-dose risperidone treatment.