Neuroscience
-
The anterior cingulate cortex (ACC) has been demonstrated to play an important role in the affective dimension of pain. Although much evidence has pointed to an increased excitatory synaptic transmission in the ACC in some of the pathological pain state, the inhibitory synaptic transmission in this process has not been well studied. Also, the overall changes of excitatory and inhibitory synaptic transmission have not been comparatively studied in an animal model displaying both long-term persistent nociception and hyperalgesia. ⋯ The recordings of miniature post-synaptic currents demonstrate an increase in frequency of miniature excitatory post-synaptic currents (mEPSCs) and a decrease in both frequency and amplitude of miniature inhibitory post-synaptic currents (mIPSCs) in rats' ACC slice of bee venom treatment. Taken together, the present results demonstrate an unparalleled change between excitatory and inhibitory synaptic transmission in the ACC under a state of peripheral persistent nociception that might be underlying mechanisms of the excessive excitability of the ACC neurons. We propose that the painful stimuli when lasts or becomes persistent may cause a disruption of the balance between excitatory and inhibitory synaptic transmission that can contribute to the functional change in the ACC.
-
The Ts65Dn (TS) mouse is the most widely used model of Down syndrome (DS). This mouse shares many phenotypic characteristics with the human condition including cognitive and neuromorphological alterations. In this study the effects of physical exercise on hippocampal neurogenesis and behavior in TS mice were assessed. 10-12 month-old male TS and control (CO) mice were submitted to voluntary physical exercise for 7 weeks and the effects of this protocol on hippocampal morphology, neurogenesis and apoptosis were evaluated. ⋯ Voluntary physical exercise did not rescue these alterations in TS mice but it did increase the number of doublecortin (DCX)-and phospho histone 3 (PH3)-positive neurons in CO mice. It is concluded that physical exercise produced a modest anxiolytic effect in CO mice and that this was accompanied by an increased number of immature cells in the hippocampal DG. On the other hand, voluntary physical exercise exerted a positive effect on TS mice learning of the platform position in the Morris water maze that seems to be mediated by a neurogenesis-independent mechanism.
-
Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor Fibroblast growth factor-inducible 14 (Fn14) are expressed in neurons. Here we demonstrate that TWEAK induces a dose-dependent increase in neuronal death and that this effect is independent of tumor necrosis factor alpha (TNF-α) and mediated by nuclear factor-kappa B (NF-κB) pathway activation. Incubation with TWEAK induces apoptotic cell death in wild-type (Wt) but not in Fn14 deficient (Fn14(-/-)) neurons. ⋯ Experimental middle cerebral artery occlusion (MCAO) increases the expression of TWEAK and Fn14 mRNA and active caspase-3, and the cleavage of poly(ADP-ribose) polymerase-1 (PARP-1) with accumulation of PAR in the ischemic area in Wt but not Fn14(-/-) mice. Together, these results suggest a model where in response to hypoxia/ischemia the interaction between TWEAK and Fn14 in neurons induces PARP-1 activation with accumulation of PAR polymers and cell death via NF-κB pathway activation. This is a novel pathway for hypoxia/ischemia-induced TWEAK-mediated cell death and a potential therapeutic target for ischemic stroke.
-
Brain damage, such as ischemic stroke, enhances proliferation of neural stem/progenitor cells (NSPCs) in the subventricular zone (SVZ). To date, no reliable in vitro systems, which can be used to unravel the potential mechanisms underlying this lesion-induced effect, have been established. Here, we developed an ex vivo method to investigate how the proliferation of NSPCs changes over time after experimental stroke or excitotoxic striatal lesion in the adult rat brain by studying the effects of microglial cells derived from an injured brain on NSPCs. ⋯ Furthermore, we found that NSPCs derived from injured brains were more likely to differentiate into neurons and oligodendrocytes than astrocytes. Our ex vivo system reliably mimics what is observed in vivo following brain injury. It constitutes a powerful tool that could be used to identify factors that promote NSPC proliferation and differentiation in response to injury-induced activation of microglial cells, by using tools such as proteomics and gene array technology.
-
Traumatic brain injury (TBI) causes massive brain damage. However, the secondary injury and temporal sequence of events with multiple mechanisms after the insult has not been elucidated. Here, we examined the occurrence of apoptosis and a causal relationship between inflammation and apoptosis in the TBI brain. ⋯ Interestingly, the expression profile of CD68 macrophage labeled cells closely resembled that of apoptotic cells after TBI, including the role of inflammatory signaling pathway in the progression of apoptotic cell death. These results taken together suggest that TBI induced upregulation of apoptosis-related genes, concomitant with the detection of apoptotic brain pathology during the 3-48 h post-injury period, which may be likely mediated by inflammation. Therapies designed at abrogating apoptosis and/or inflammation may prove effective when initiated at this subacute TBI phase.