Despite the negative acceleration results in this study, the main finding suggests that hyperactive hypothalamic pituitary thyroid axis may be associated with better antidepressant response. Further research is needed to further explore this potential marker. Acknowledgments The study was funded from
by a grant from the American Foundation of Suicide Prevention (AFSP) PI: MAF. Conflict of Interest None declared.
Neurotrophic factors regulate Inhibitors,research,lifescience,medical plasticity, promote survival, and protect adult neurons from toxins and injury (reviewed by Petrova et al. 2004 and Lindholm and Saarma 2010). They are therefore considered potential drug candidates for the treatment of neurodegenerative diseases, such as Parkinson’s
disease (PD), where progressive loss of midbrain dopamine (DA) neurons affects motor performance (Dauer and Przedborski 2003). Cerebral dopamine neurotrophic Inhibitors,research,lifescience,medical factor (CDNF) and mesencephalic astrocyte–derived neurotrophic factor (MANF) represent an evolutionary conserved family of neurotrophic factors (Lindholm et al. 2007; Parkash et al. 2009; Lindholm and Saarma 2010). In a rat 6-hydroxydopamine (6-OHDA) model of PD, single injections of CDNF and MANF proteins were able to restore function and increase survival of midbrain DA neurons (Lindholm et al. 2007; Voutilainen et Inhibitors,research,lifescience,medical al. 2009). In the same model, also a 2-week continuous infusion of CDNF attenuated the degeneration of the nigrostriatal DAergic system (Voutilainen Inhibitors,research,lifescience,medical et al. 2011). CDNF had also a significant neuroprotective and neurorestorative ��-catenin signaling effect in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD (Airavaara et al. 2012). In addition, MANF had survival-promoting effect on DA neurons in vitro (Petrova et al. 2003), and intracellularly delivered MANF
was able to block Bax-induced neuronal apoptosis (Hellman et al. 2011). The invertebrate analog Drosophila melanogaster MANF (DmMANF) has also been proven to be crucial for the maturation of the nervous system and Inhibitors,research,lifescience,medical for the maintenance of DAergic neurons in D. melanogaster (Palgi et al. 2009). These observations point out a possible implication for CDNF/MANF family of neurotrophic factors all in the treatment of PD. Glial cell line–derived neurotrophic factor (GDNF) has been considered the most promising neurotrophic factor, showing positive effects in several animal models of PD (Hoffer et al. 1994; Kearns and Gash 1995; Tomac et al. 1995a; Gash et al. 1996; Zhang et al. 1997; Kirik et al. 2004), but not in the α-synuclein model of PD (Decressac et al. 2011). Controversial results from clinical trials with GDNF (Gill et al. 2003; Nutt et al. 2003; Slevin et al. 2005; Lang et al. 2006) have pointed out the importance of effective and reliable administration techniques (discussed by Sherer et al. 2006; Ramaswamy et al. 2009).