Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:A7KAX9 (grit)
 1,275 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In pigeons, asymmetric photic stimulation around hatch induces functional visual asymmetries that are accompanied by left-right differences in tectal cell sizes. Different aspects of light-dependent neuronal differentiation are known to be mediated by the brain-derived neurotrophic factor (BDNF). Therefore, we investigated by means of single or triple BDNF- or saline-injections into the right eye of dark-incubated pigeon hatchlings if ocular BDNF enrichment mimics the effects of biased visual input. As adults, the birds were tested in a grit-grain discrimination task to estimate the degree and direction of visual lateralization followed by a morphometric analysis of retinal and tectal cells. The grit-grain discrimination task demonstrated that triple BDNF-injections enhanced visuoperceptual and visuomotor functioning of the left eye system. Morphometric analysis showed bilateral cell-type dependent effects within the optic tectum. While single-BDNF injections increased cell body sizes of calbindin-positive efferent neurons, triple-injections decreased cell sizes of parvalbumin-positive cells. Moreover, single BDNF-injections increased retinal cell sizes within the contralateral eye. Analysis of BDNF-induced intracellular signaling demonstrated enhanced downstream Ras activation for at least 24 h within both tectal halves whereas activity changes within the contralateral retina could not be detected. This points to primarily tectal effects of ocular BDNF. In sum, exogenous BDNF modulates the differentiation of retinotectal circuitries and dose-dependently shifts lateralized visuomotor processing towards the noninjected side. Since these effects are opposite to embryonic light stimulation, it is unlikely that the impact of light onto asymmetry formation is mediated by retinal BDNF.
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PMID:Breaking the balance: ocular BDNF-injections induce visual asymmetry in pigeons. 1850 70

A crucial step in the development of the vertebrate visual system is the branching of retinal ganglion cell (RGC) axons within their target, the superior colliculus/tectum. A major player in this process is the neurotrophin brain-derived neurotrophic factor (BDNF). However, the molecular basis for the signaling pathways mediating BDNF action is less well understood. As BDNF exerts some of its functions by controlling the expression of microRNAs (miRNAs), we investigated whether miRNAs are also involved in BDNF-mediated retinal axon branching. Here, we demonstrate that the expression pattern of miRNA-132 in the retina is consistent with its involvement in this process, and that BDNF induces the upregulation of miRNA-132 in retinal cultures. Furthermore, in vitro gain-of-function and loss-of-function approaches in retinal cultures reveal that miRNA-132 mediates axon branching downstream of BDNF. A known target of miRNA-132 is the Rho family GTPase-activating protein, p250GAP. We find that p250GAP is expressed in RGC axons and mediates the effects of miRNA-132 in BDNF-induced branching. BDNF treatment or overexpression of miRNA-132 leads to a reduction in p250GAP protein levels in retinal cultures, whereas the overexpression of p250GAP abolishes BDNF-induced branching. Finally, we used a loss-of-function approach to show that miRNA-132 affects the maturation of RGC termination zones in the mouse superior colliculus in vivo, while their topographic targeting remains intact. Together, our data indicate that BDNF promotes RGC axon branching during retinocollicular/tectal map formation via upregulation of miRNA-132, which in turn downregulates p250GAP.
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PMID:BDNF promotes axon branching of retinal ganglion cells via miRNA-132 and p250GAP. 2443 55

Electroacupuncture (EA) has shown protective effects on cognitive decline. However, the underlying molecular mechanisms are ill-understood. The present study was undertaken to determine whether the cognitive function was ameliorated in cerebral hypoperfusion rats following EA and to investigate the role of PKA/CREB pathway. We used a rat 2-vessel occlusion (2VO) model and delivered EA at Baihui (GV20) and Dazhui (GV14) acupoints. Morris water maze (MWM) task, electrophysiological recording, Golgi silver stain, Nissl stain, Western blot, and real-time PCR were employed. EA significantly (1) ameliorated the spatial learning and memory deficits, (2) alleviated long-term potentiation (LTP) impairment and the reduction of dendritic spine density, (3) suppressed the decline of phospho-CREB (pCREB) protein, brain-derived neurotrophic factor (BDNF) protein, and microRNA132 (miR132), and (4) reduced the increase of p250GAP protein of 2VO rats. These changes were partially blocked by a selective protein kinase A (PKA) inhibitor, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoline-sulfonamide (H89), suggesting that the PKA/CREB pathway is potentially involved in the effects of EA. Moreover, any significant damage to the pyramidal cell layer of CA1 subregion was absent. These results demonstrated that EA could ameliorate learning and memory deficits and alleviate hippocampal synaptic plasticity impairment of cerebral hypoperfusion rats, potentially mediated by PKA/CREB signaling pathway.
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PMID:Electroacupuncture Ameliorates Learning and Memory and Improves Synaptic Plasticity via Activation of the PKA/CREB Signaling Pathway in Cerebral Hypoperfusion. 2782 66