Neuroscience
-
Following spinal cord trauma, axonal regeneration in the mammalian spinal cord does not occur and functional recovery may be further impeded by retrograde neuronal death. By contrast, lampreys recover after spinal cord injury (SCI) and axons re-connected to their targets in spinal cord. However, the identified reticulospinal (RS) neurons located in the lamprey brain differ in their regenerative capacities - some are good regenerators, and others are bad regenerators - despite the fact that they have analogous projection pathways. ⋯ Here we report that, after SCI, expression of RGMa mRNA was upregulated around the transection site, while its receptor Neogenin continued to be synthesized almost inclusively in the "bad-regenerating" RS neurons. Inhibition of Neogenin by MO prohibited activation of caspases and improved the survival of RS neurons at 10 weeks after SCI. These data provide new evidence in vivo that Neogenin is involved in retrograde neuronal death and failure of axonal regeneration after SCI.
-
Tinnitus is thought to be triggered by aberrant neural activity in the central auditory pathway and is often accompanied by comorbidities of emotional distress and anxiety, which imply maladaptive functional connectivity to limbic structures, such as the amygdala and hippocampus. Tinnitus patients with normal audiograms can also have accompanying anxiety and depression, clinically. To test the role of functional connectivity between the central auditory pathway and limbic structures in patients with tinnitus with normal audiograms, we developed a murine noise-induced tinnitus model with a temporary threshold shift (TTS). ⋯ We found increased fMRI responses with amplitude of low-frequency fluctuation (ALFF) in the auditory cortex and decreased ALFF in the amygdala and hippocampus at day 1, but decreased ALFF in the auditory cortex and increased ALFF in the amygdala at day 28 post-noise exposure in tinnitus mice. Decreased functional connectivity between auditory brain regions and limbic structures was demonstrated at day 28 in tinnitus mice. Therefore, aberrant neural activities in tinnitus mice with TTS involved not only the central auditory pathway, but also limbic structures, and there was maladaptive functional connectivity between the central auditory pathway and limbic structures, such as the amygdala and hippocampus.
-
Thrombospondins (TSPs) are cell adhesion molecules that play an important role in the maintenance of hearing and afferent synaptic connections. Based on their reported function in restoring synaptic connections after stroke, we tested a potential role for TSP1 and TSP2 genes in repairing cochlear synapses following noise injury. We observed a tonotopic gradient in the expression of TSP1 and TSP2 mRNA in control mouse cochleae and an upregulation of these genes following noise exposure. ⋯ Noise trauma affecting mid to high frequencies triggered severe seizures in the TSP2-/- mice. We found that decreased susceptibility to audiogenic seizures in TSP1-/- mice was correlated with increased TSP2 protein levels in their inner ears, suggesting that TSP2 might functionally compensate for the loss of TSP1 in these mice. Our data indicate that TSP1 and TSP2 are both involved in susceptibility to NIHL, with TSP2 playing a more prominent role.
-
Lipoxin A4 (LXA4) has been reported to reduce inflammation in experimental subarachnoid hemorrhage (SAH), but the mechanism remains unclear. In this study, we investigated the role of LXA4 in inflammation-mediated cerebrovascular endothelial dysfunction and the potential mechanism after SAH. SAH was induced by endovascular perforation in male Sprague-Dawley rats, and recombinant LXA4 was injected intracerebroventricularly 1.5 h after the operation. ⋯ The administration of LXA4 significantly ameliorated endothelial dysfunction, recovered microflow, and suppressed the inflammation and infiltration of neutrophils in SAH rats. The underlying mechanism of this outcome may involve the LXA4/FPR2/ERK1/2 pathway. LXA4 might be a promising candidate for acute SAH treatment.
-
It is commonly recognized that physical exercise positively affects several CNS regions and improves cognitive abilities. For example, exercise is associated with an increase in neurogenesis and facilitation of long-term potentiation in the hippocampus. Conversely, animal models for depression are associated with a decrease in neurogenesis and a reduction of long-term potentiation in the hippocampus. ⋯ Unexpectedly, in dexamethasone-exposed animals, dentate gyrus long-term potentiation was facilitated, whereas long-term potentiation in CA1 was unaffected by prenatal dexamethasone or by 10 or 21 days of voluntary running. Irrespective of age, prenatal dexamethasone and running had limited effects on synaptic transmission and presynaptic release in CA1 and dentate gyrus. In summary, running facilitates dentate gyrus long-term potentiation in adult animals that resembles the effects of prenatal dexamethasone.