Neuroscience
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Deep brain stimulation (DBS) of the medial forebrain bundle (MFB) induces rapid improvement of depressive symptoms in patients suffering from treatment-refractory major depressive disorder (MDD). It has been hypothesized that activation of the dopamine (DA) system contributes to this effect. To investigate whether DBS in the MFB affects DA release in the striatum, we combined DBS with fast-scan cyclic voltammetry (FSCV) in freely moving rats. ⋯ These findings suggest that effects of DBS in the MFB are mediated by an acute change in extracellular DA concentration, but more research is needed to further explore the potentially sustained duration of this effect. Together, our results provide both support and refinement of the hypothesis that MFB DBS activates the DA system: DBS induces an increase in overall ambient concentration of DA, but spontaneous or reward-associated more rapid, phasic DA dynamics are not enhanced. This knowledge improves our understanding of how DBS affects brain function and may help improve future therapies for depressive symptoms.
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Neurogenesis in the subventricular zone (SVZ) plays a vital role in neurologic recovery after stroke. However, only a small fraction of newly generated neuroblasts from the SVZ will survive long-term. Successful migration and survival of neuroblasts requires angiogenesis, lesion-derived chemo-attractants, and appropriate local microenvironments, which are partly regulated by the platelet-derived growth factor receptor (PDGFR) signaling pathway. ⋯ Crenolanib treatment increased the apoptosis of pericytes and decreased the pericyte/vascular coverage, but had no effects on apoptosis of astrocytes. We conclude that the PDGFR signaling pathway plays a vital role in the SVZ neurogenesis after stroke. It can also affect angiogenesis, lesion-derived chemo-attractants, and the local microenvironment, which are all important to stroke-induced neurogenesis.
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The transition from multipotent neural stem cells (NSCs) to terminally differentiated neurons is a multistep process, and the transition is finely regulated by transcription factors with basic helix-loop-helix (bHLH) motifs. Melatonin is an endogenous neurohormone with profound neurotrophic and neuroprotective effects both during the embryonic developmental stage and adulthood. The effects of melatonin on the differentiation of NSCs have been reported, and these effects may be responsible for its neuroprotective properties. ⋯ Increased H3K14 acetylation altered the chromatin state of the promoters of bHLH factors Neurogenin1 and NeuroD1 and activated their transcription; then, Neurogenin1 and NeuroD1 initiated and sustained the commitment to neuronal fates. As we know, CBP/p300 is an important class of histone acetyltransferases that acetylate histone H3K14, we found that melatonin activated the histone acetyltransferase activity of CREB-binding protein (CBP)/p300 via ERK signaling pathways. For the first time, we systematically showed the molecular mechanism of action of melatonin, which suggested that melatonin functions as a regulator of the acetylation-dependent gene expression network.
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Secondary neuronal degeneration (SND) occurring in Traumatic brain injury (TBI) consists in downstream destructive events affecting cells that were not or only marginally affected by the initial wound, further increasing the effects of the primary injury. Glutamate excitotoxicity is hypothesized to play an important role in SND. TBI is a common cause of olfactory dysfunction that may be spontaneous and partially recovered. ⋯ A lack of correlation between OB volumes and olfactory function was observed. An increase in SVZ neurogenesis (Ki67+ cells, PSANCAM+ cells (p<0.01) associated with an increase in OB glomerular dopaminergic immunostaining (p<0.05) were related to olfactory function recovery. The present results show that changes in OB volumes cannot explain the recovery of the olfactory function and suggest a relevant role for dopaminergic OB interneurons in the pathophysiology of recovery of loss of smell in TBI.
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The present study characterized quantitatively sexual dimorphic development of gyrification by MRI-based morphometry. High spatial-resolution 3D MR images (using RARE sequence with short TR and minimum TE setting) were acquired from fixed brain of male and female ferrets at postnatal days (PDs) 4-90 using 7-tesla preclinical MRI system. The gyrification index was evaluated either throughout the cerebral cortex (global GI) or in representative primary sulci (sulcal GI). ⋯ In the sulcal GI, sulcus-specific male-over-female GI was revealed in the rhinal fissure, and presylvian sulcus on PD 42, and additionally in the coronal, splenial, lateral, and caudal suprasylvian sulci on PD 90. The current results suggest that age-related sexual dimorphism of the gyrification was biphasic in the ferret cortex. A male-over-female gyrification was allometric by PD 21, and was thereafter specific to primary sulci located on phylogenetically newer multimodal cortical regions.