Monoaminergic regulation of Sonic hedgehog signaling cascade expression in the adult rat hippocampus

Department of Biological Sciences, Tata Institute of Fundamental Research (TIFR), Homi Bhabha Road, Mumbai 400005, India.
Neuroscience Letters (Impact Factor: 2.03). 05/2009; 453(3):190-4. DOI: 10.1016/j.neulet.2009.02.034
Source: PubMed


Monoamines are implicated in the modulation of adult hippocampal neurogenesis in depression models and following chronic antidepressant treatment. Given the key role of Sonic hedgehog (Shh) in adult neurogenesis, we examined whether monoaminergic perturbations regulate the expression of Shh or its co-receptors Smoothened (Smo) and Patched (Ptc). Combined depletion of both serotonin and norepinephrine with para-chlorophenylalanine (PCPA) resulted in a significant decrease in Smo and Ptc mRNA within the dentate gyrus subfield of the hippocampus. However, selective depletion of serotonin, using the serotonergic neurotoxin 5,7-dihyrdroxytryptamine (5,7-DHT), or norepinephrine, using the noradrenergic neurotoxin DSP-4, did not alter expression of Shh and its co-receptors, Smo and Ptc. Acute treatment with the monoamine releasing agent, para-chloroamphetamine (PCA) significantly upregulated Smo mRNA within the dentate gyrus. However, acute or chronic treatment with pharmacological antidepressants that modulate monoaminergic neurotransmission did not regulate Shh cascade expression. These results indicate that robust changes in monoamine levels can regulate the expression of the Shh signaling cascade in the adult rodent brain.

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    • "s . These results thus indicate that robust changes in monoamine levels may be needed to alter the expression of the Shh signaling cascade in the adult rodent brain ( Rajendran et al . 2009 ) . Acute and chronic treatments with pharmacological antidepressants that modulate monoaminergic neurotrans - mission do not regulate Shh cascade expression ( Rajendran et al . 2009 ) . In contrast electroconvulsive seizures , a potent treatment for major depressive disorders , induce a rapid up - regulation of the transcriptional target Ptc , but also a rapid and robust reduction in Smo transcription in the dentate gyrus ( Banerjee et al . 2005 ) . Moreover , Cyclopamine is able to block electroconvulsive seizures"
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    • "More recently, Shh was found to be a crucial signal for adult neurogenesis, particularly in maintaining stem cell selfrenewal and acting as a mitogen in the SVZ and SGZ (Palma et al., 2005; Ahn and Joyner, 2005; Wang et al., 2007; Han et al., 2008). Changes in monoamine levels in vivo through chemical depletion have been shown to regulate the expression of the Shh signaling cascade in the adult rodent brain measured with in situ hybridization (Rajendran et al., 2009). The same group also reported that electroconvulsive seizures upregulated Shh signaling pathways at the mRNA level in the SGZ (Banerjee et al., 2005). "
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