Disease relevance of Pspn

• Here, we report that mice lacking Pspn by homologous recombination show normal development and behavior, but are hypersensitive to cerebral ischemia [1].
• Neuronal cell death can be prevented or markedly attenuated by administration of recombinant human PSP in vivo before ischemia in both mouse and rat models [1].
• We find that glutamate-induced Ca(2+) influx, thought to be a major component of ischemic neuronal cell death, can be regulated directly by the Persephin protein (PSP) and that PSP can reduce hypoxia/reperfusion cell death in vitro [1].
• Here we show that neurturin, artemin and GDNF, but not persephin, promote axonal initiation in cultured dorsal root ganglion neurons from young adult mice [2].
• They indicate that PSP is a recurrent toxicity in molluscs along the Mediterranean shore of Morocco [3].

High impact information on Pspn

• Our findings support the view that PSP signaling can exert an important control function in the context of stroke and glutamate-mediated neurotoxicity, and also suggest that future therapeutic approaches may involve this novel trophic protein [1].
• Taken together, these data indicate that PSP is a potent modulator of excitotoxicity in the central nervous system with pronounced neuroprotective activity [1].
• Human glial cell line-derived neurotrophic factor receptor alpha 4 is the receptor for persephin and is predominantly expressed in normal and malignant thyroid medullary cells [4].
• Neurturin, artemin and persephin are homologs of GDNF, and their impact on axonal regeneration in adults has not been studied yet [2].
• Glial cell line-derived neurotrophic factor family receptor (GFRalpha) 4, the binding receptor for persephin, is coexpressed with the signaling Ret receptor tyrosine kinase predominantly in thyroid calcitonin-producing C cells [5].

Biological context of Pspn

• However, in 33% of cells studied in Kcna1-null slices bathed in normal extracellular medium, orthodromic stimulation evoked synaptically driven bursts of action potentials that followed a short-latency excitatory postsynaptic potential (EPSP)-inhibitory PSP (IPSP) sequence [6].
• Although it is clear that female sexual behavior, including pacing behavior, is important for induction of P/PSP, there has been no concerted effort to examine whether or how common mechanisms may control both functions [7].
• High-level parotid gland expression of the PSP gene was indicated to depend on a novel regulatory region situated between -8.0 and -6.5 kb [8].
• This region was shown to activate a heterologus SV40 early promoter in the parotid glands of transgenic mice, suggesting that the PSP gene is controlled by enhancer sequences [8].
• This paper will review both new and old data that address the question of whether brain mechanisms involved in reproductive function act in a coordinated way to control female sexual behavior and the induction of pregnancy/pseudopregnancy (P/PSP) by vaginocervical stimulation [7].

Anatomical context of Pspn

• To begin to address this issue, we have studied expression and putative functions of GDNF, NTN, PSP, and their receptors in two cell lines representing models for oligodendrocyte progenitor cells (OLI-neu) and immature oligodendrocytes (OLN-93), respectively [9].
• The murine PSP gene is expressed at a high-level in the parotid glands [8].
• Immunostaining of tumor tissues with antibody against the endothelial cell marker (Factor VIII) demonstrated a positive correlation in that both the vascular density and tumor weight were lower in mice treated with PSP [10].

Associations of Pspn with chemical compounds

• PSP toxin, anatoxin-a, homoanatoxin-a and microcystins were not detected when pond water from a diseased pond was tested [11].
• Spatial and temporal evolution of PSP toxins along the Atlantic shore of Morocco [12].
• NIH/Ola mice were given two intraperitoneal injections with ovalbumin (OVA; 10 microg) alone or OVA in combination with PSP, polytetrafluoroethylene (teflon), titanium dioxide (TiO(2)) or amorphous silica particles (2.8x10(10)-2.8x10(12)) [13].

Other interactions of Pspn

• This approach has assisted the identification of four collecting-duct morphogens: hepatocyte growth factor, glial cell line-derived neurotrophic factor, nerturin and persephin [14].

References