2024-03-29T05:04:50Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/502622017-02-27T16:38:22Zcom_10261_11773com_10261_1col_10261_11774
Hidalgo Figueroa, María
Bonilla, Sonia
Gutiérrez, Francisco
Pascual Bravo, Alberto
López-Barneo, José
2012-05-28T13:03:00Z
2012-05-28T13:03:00Z
2012-01-18
Journal of Neuroscience 32(3): 864-872 (2012)
0270-6474
PMID: 22262884
http://hdl.handle.net/10261/50262
10.1523/JNEUROSCI.2693-11.2012
1529-2401
Glial cell line-derived neurotrophic factor (GDNF) is absolutely required for survival of dopaminergic (DA) nigrostriatal neurons and protect them from toxic insults. Hence, it is a promising, albeit experimental, therapy for Parkinson's disease (PD). However, the source of striatal GDNF is not well known. GDNF seems to be normally synthesized in neurons, but numerous reports suggest GDNF production in glial cells, particularly in the injured brain. We have studied in detail striatal GDNF production in normal mouse and after damage of DA neurons with MPTP. Striatal GDNF mRNA was present in neonates but markedly increased during the first 2–3 postnatal weeks. Cellular identification of GDNF by unequivocal histochemical methods demonstrated that in normal or injured adult animals GDNF is expressed by striatal neurons and is not synthesized in significant amounts by astrocytes or microglial cells. GDNF mRNA expression was not higher in reactive astrocytes than in normal ones. Approximately 95% of identified neostriatal GDNF-expressing cells in normal and injured animals are parvalbumin-positive (PV+) interneurons, which only represent ∼0.7% of all striatal neurons. The remaining 5% of GDNF+ cells are cholinergic and somatostatin+ interneurons. Surprisingly, medium spiny projection neurons (MSNs), the vast majority of striatal neurons that receive a strong DA innervation, do not express GDNF. PV+ interneurons constitute an oscillatory functional ensemble of electrically connected cells that control MSNs' firing. Production of GDNF in the PV+ neurons might be advantageous to supply synchronous activity-dependent release of GDNF in broad areas of the striatum. Stimulation of the GDNF-producing striatal PV+ ensemble in PD patients could have therapeutic effects.
eng
openAccess
Dopamine
Glial cell line
Nerve tissue proteins
Parvalburnings
Green fluorescent proteins
Choline O-acetyltransferase
GDNF Is Predominantly Expressed in the PV+ Neostriatal Interneuronal Ensemble in Normal Mouse and after Injury of the Nigrostriatal Pathway
artículo