PMID- 12031278
OWN - NLM
STAT- MEDLINE
DCOM- 20020716
LR  - 20220330
IS  - 0361-9230 (Print)
IS  - 0361-9230 (Linking)
VI  - 57
IP  - 6
DP  - 2002 Apr
TI  - Neuroprotection by neurotrophins and GDNF family members in the excitotoxic model 
      of Huntington's disease.
PG  - 817-22
AB  - Huntington's disease is a neurodegenerative disorder characterized by a selective 
      degeneration of striatal projection neurons, which deal with choreic movements. 
      Neuroprotective therapy could be achieved with the knowledge of the specific 
      trophic requirements of these neuronal populations. Thus, the induction of 
      endogenous trophic response or the exogenous administration of neurotrophic 
      factors may help to prevent or stop the progression of the illness. 
      Excitotoxicity has been implicated in the etiology of Huntington's disease, 
      because intrastriatal injection of glutamate receptor agonists reproduces some of 
      the neuropathological features of this disorder. Activation of glutamate 
      receptors in the striatum differentially regulates the expression of 
      neurotrophins, glial cell line-derived neurotrophic factor (GDNF), neurturin, and 
      their receptors in the striatum and in its connections, cortex, and substantia 
      nigra, showing a selective trophic response against excitotoxic insults. 
      Transplantation of cells genetically engineered to release neurotrophic factors 
      in the striatum has been used to study the neuroprotective effects of 
      neurotrophin and GDNF family members in the excitotoxic model of Huntington's 
      disease. Neurotrophins (brain-derived neurotrophic factor [BDNF], neurotrophin-3, 
      and neurotrophin-4) protected striatal projection neurons against quinolinic or 
      kainic acid treatment. However, GDNF family members showed a more specific 
      action. Neurturin only protected gamma-aminobutyric acid (GABA)/enkephalinergic 
      neurons that project to the external segment of the globus pallidus, whereas GDNF 
      exerts its effects on GABA/substance P positive neurons, which project to the 
      substantia nigra pars compacta and the internal segment of the globus pallidus. 
      In conclusion, the trophic requirements of each population of striatal projection 
      neurons are due to a complex interaction between several neurotrophic factors, 
      such as neurotrophins and GDNF family members, which can be modified, in 
      different pathological conditions. Moreover, these neurotrophic factors may be 
      able to provide selective protection for basal ganglia circuits, which are 
      affected in striatonigral degenerative disorders, such as Huntington's disease or 
      multisystem atrophy.
FAU - Alberch, J
AU  - Alberch J
AD  - Departament de Biologia Cel.lular i Anatomia Patologica, Facultat de Medicina, 
      IDIBAPS, Universitat de Barcelona, Barcelona, Spain. alberch@medicina.ub.es
FAU - Perez-Navarro, E
AU  - Perez-Navarro E
FAU - Canals, J M
AU  - Canals JM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United States
TA  - Brain Res Bull
JT  - Brain research bulletin
JID - 7605818
RN  - 0 (GDNF protein, human)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Neurotoxins)
RN  - 0 (Receptors, Glutamate)
SB  - IM
MH  - Animals
MH  - Basal Ganglia/metabolism/physiopathology/*surgery
MH  - Glial Cell Line-Derived Neurotrophic Factor
MH  - Humans
MH  - Huntington Disease/metabolism/physiopathology/*therapy
MH  - Models, Neurological
MH  - Nerve Growth Factors/metabolism/*therapeutic use
MH  - Nerve Tissue Proteins/metabolism/*therapeutic use
MH  - Neurons/*metabolism/pathology
MH  - Neuroprotective Agents/metabolism/*therapeutic use
MH  - Neurotoxins/*metabolism
MH  - Receptors, Glutamate/drug effects/*metabolism
RF  - 69
EDAT- 2002/05/29 10:00
MHDA- 2002/07/18 10:01
CRDT- 2002/05/29 10:00
PHST- 2002/05/29 10:00 [pubmed]
PHST- 2002/07/18 10:01 [medline]
PHST- 2002/05/29 10:00 [entrez]
AID - S0361923001007754 [pii]
AID - 10.1016/s0361-9230(01)00775-4 [doi]
PST - ppublish
SO  - Brain Res Bull. 2002 Apr;57(6):817-22. doi: 10.1016/s0361-9230(01)00775-4.