GDNF

Neurosciences Journal Club Motor Neurons
Ligand (receptor) GDNF (not known) Survival in vivo ++++ Protect/rescue in vivo Neonatal axotomy: survival, no  atrophy Adult axotomy: ChAT phenotype

Ogan Gurel, CC4 7 September 1995 Dopaminergic Neurons
Survival in vivo +++ Protect/rescue in vivo Adult axotomy: survival, TH  phenotype MPTP toxicity: protection and  recovery of TH, dopamine  metabolites, motor behaviors ­ Adult axotomy: survival

CNTF (CNTFR­α) NGF (TrkA) BDNF (TrkB) NT­4/5 (TrkB) FGF (FGFR) PDGF  (PDGFR) IGF­1 (IGF­1R)

++(+)

Neonatal axotomy: survival Efficacy in mice with motor  neuron disease: pmn, Wobbler

­ ++++ ++++ +(+) Not  known Not  known Not known Neonatal axotomy: survival; Adult axotomy: ChAT phenotype Adult axotomy: ChAT phenotype +++ ++++ Indirect ++ + Adult axotomy: survival, TH  phenotype Adult axotomy: survival, TH  phenotype MPTP toxicity: survival, TH  phenotype dopamine Not known Not known

Tomac A, et al., Nature, Vol 373,  26 Jan 1995, pp. 335–339.
Used   MPTP   to   induce   dopamine   (DA)  depletion   in   the   striatum   and   loss   of  DA cell bodies in the substantia nigra  (SN). Fig 1 Biochemistry:     Protection   and  regeneration   of   striatal   dopamine  levels   with   SN   or   striatal   injections  of  GDNF;  striatum   >   SN   (GDNF   may   work  as a target­derived GF), also  increase  DA   metabolites,   also   contralateral  effects (due to diffusion?). Fig 2 Immunohistochemistry:   Protection  & regeneration of striatum by GDNF. Fig 3 Motor behavior: protection and regeneration with increased activity over control.

Beck KD, et al., Nature, Vol 373, 26 Jan 1995, pp. 339–341.
Used transection of medial forebrain bundle to induce loss of DA neurons in the SN. Fig 1/ 2 Table 2 Immunohistochemistry: demonstrating ↑ in TH+ neurons in SN treated with GDNF GDNF (not TGFα, bFGF or NT­4/5)

Yan Q, et al.,  Nature, Vol 373, 26 Jan 1995, pp. 341–344.

Used transection of facial nerve to induce loss of motor neurons (facial nucleus) Fig 1 Autoradiography  of  125I labelled GDNF showed uptake by motor neurons in a specific,  saturable receptor­mediated fashion Fig 2 Immunohistochemistry: demonstrating prevention in neonates of axotomy­induced motor  neuron death by GDNF Fig 3 Immunohistochemistry:   Loss   of   AChT   activity   in   adult   mice   facial   nuclei   is   also  prevented by GDNF

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