GDNF

links: reference: 10-18-2021

Glial cell line-derived neurotrophic factor #

• Elevated endogenous GDNF induces altered dopamine signalling in mice and correlates with clinical severity in schizophrenia
  • 2-3x GDNF = increased striatal presynaptic dopamine leading to reduction of PFC dopamine.
    • I have heard Jarvoss say that this 2x increas is the threshold needed, and increases in GDNF lower than that may not lead to abnormalities. He may just be talking out his ass though
  • In striatal interneurons, A2A -> cAMP -> GDNF -> activation of GDNF receptor RET in SN dopamine neurons -> Dopamine release in the dorsal striatum
    • Leads to reduced Mesocortical Pathway dopamine innervation and dopamine signalling in the prefrontal cortex, via a yet unknown mechanism.
      • Reduced number of “DAT+” dopaminergic synaptic boutons in the mPFC and in the association cortex in the GDNF transgenic mice.
  • Chronic Istradefylline normalized striatal GDNF, reducing DA release from Substantia Nigra, and/thus normalizing DA signalling in Nigrostriatal Pathway.
    • What I don’t know is how istra directly leads to an increase/normalization in Mesocortical Pathway doapmine.
    • I might add this is chronic istradefylline as well.
• Mainly acts via the RTK RET (rearranged during transfection).
• DNSP11 is a GDNF mimetic peptide that Picard is working on or something. Says it’s incredible.