Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, clinical and animal studies have shown that neuronal and glial plasticity are important for the therapeutic action of antidepressants. Thus, it has been suggested that neurotrophic factors or growth factors, which are potent regulators for neuronal and glial plasticity, might be involved in the effect of antidepressants. Post-mortem studies provide evidence for glial reduction in different brain areas in mood disorders. Therefore, we focused on glial cell line-derived neurotrophic factor (GDNF) in mood disorders, because GDNF plays an important role in neurogenesis and high-ordered brain function, such as learning and memory. GDNF family ligands have shown promise of efficacy for neurodegenerative disorders such as Parkinson's disease, suggesting that GDNF family ligands exist in the closest position to clinical development for treatment of diseases of the central nervous system. We reported that total GDNF levels in whole blood in patients with mood disorders were significantly lower than those in healthy control subjects (Takebayashi et al, 2006), and antidepressants increased GDNF production through monoamine-independent activation of protein tyrosine kinase (PTK) and extracellular signal-regulated kinase (ERK) in glial cells (Hisaoka et al, 2007). Clarifying the monoamine-independent novel target of antidepressants in glia might contribute to the development of more efficient therapeutics for depression.
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PMID:[Glia as targets for antidepressants: an involvement in glial cell line-derived neurotrophic factor]. 1815 38

Glutamate AMPA receptors are critical for sensory transmission at the spinal cord dorsal horn (DH). Plasma membrane AMPA receptor endocytosis that can be induced by insulin may underlie long term modulation of synaptic transmission. Insulin receptors (IRs) are known to be expressed on spinal cord DH neurons, but their possible role in sensory transmission has not been studied. In this work the effect of insulin application on fast excitatory postsynaptic currents (EPSCs) mediated by AMPA receptors evoked in DH neurons was evaluated. Acute spinal cord slices from 6 to 10 day old mice were used to record EPSCs evoked in visually identified superficial DH neurons by dorsal root primary afferent stimulation. AMPA EPSCs could be evoked in all of the tested neurons. In 75% of the neurons the size of the AMPA EPSCs was reduced to 62.1% and to 68.9% of the control values when 0.5 or 10 microM insulin was applied. There was no significant change in the size of the AMPA EPSCs in the remaining 25% of DH neurons. The membrane permeable protein tyrosine kinase inhibitor, lavendustin A (10 microM), prevented the insulin induced AMPA EPSC depression. Our results suggest a possible role of the insulin pathway in modulation of sensory and nociceptive synaptic transmission in the spinal cord.
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PMID:Modulation of AMPA excitatory postsynaptic currents in the spinal cord dorsal horn neurons by insulin. 2000 24

Proline-rich tyrosine kinase 2 (PYK2), also known as cell adhesion kinase beta or protein tyrosine kinase 2b, is a calcium-dependent signaling protein involved in cell migration. Phosphorylation of residue Y402 is associated with activation of PYK2 and leads to the recruitment of downstream signaling molecules. PYK2 was previously implicated in long-term potentiation (LTP); however, the role of PYK2 in long-term depression (LTD) is unknown. Here, we report that PYK2 is activated by NMDA receptor stimulation (chemical LTD) in cultured neurons. Small hairpin RNA-mediated knockdown of PYK2 blocks LTD, but not LTP, in hippocampal slice cultures. We find that the Y402 residue and, to a lesser extent, PYK2 kinase activity contribute to PYK2's role in LTD. Knockdown experiments indicate that PYK2 is required to suppress NMDA-induced extracellular signal-regulated kinase (ERK) phosphorylation. Overexpression of PYK2 depresses NMDA-induced ERK phosphorylation and inhibits LTP, but not LTD. Our data indicate that PYK2 is critical for the induction of LTD, possibly in part by antagonizing ERK signaling in hippocampal neurons.
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PMID:Proline-rich tyrosine kinase 2 regulates hippocampal long-term depression. 2082 62


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