Biomaterial Database

Long-term protection of the rat nigrostriatal dopaminergic system by glial cell line-derived neurotrophic factor against 6-hydroxydopamine in vivo. 1998

A M Sullivan, and J Opacka-Juffry, and S B Blunt

MRC Cyclotron Unit, Hammersmith Hospital, London, UK.

Glial cell-line-derived neurotrophic factor (GDNF) has been shown to enhance the survival of dopaminergic neurones both in vitro and in vivo, and to protect the rodent dopaminergic system from neurotoxic damage. However, most previous studies have only examined the short-term protective effects of GDNF. We have investigated the long-term effects of GDNF on a 6-hydroxydopamine (6-OHDA)-induced lesion of the rat medial forebrain bundle (MFB), which results in complete and irreversible destruction of the nigrostriatal pathway, and is a robust model of Parkinson's disease. GDNF was administered ipsilaterally above the substantia nigra and into the lateral ventricle immediately before a unilateral 6-OHDA injection into the MFB. The effects of GDNF were examined in vivo by behavioural testing and positron emission tomography (PET) at weekly intervals, for 12 weeks. GDNF prevented the development of amphetamine-induced rotations at all time-points. PET studies, using [11C]-RTI-121 as a tracer for the dopamine transporter, indicated that GDNF prevented 6-OHDA-induced reduction of dopamine reuptake sites in the ipsilateral striatum. Post-mortem neurochemical analysis at 13 weeks after surgery found that GDNF significantly inhibited 6-OHDA-induced loss of dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid in the ipsilateral striatum. Immunocytochemistry showed that GDNF reduced 6-OHDA-induced loss of tyrosine hydroxylase-positive neurones in both the substantia nigra pars compacta and ventral tegmental area. We have shown that a single treatment with GDNF can confer long-term protective effects against a 6-OHDA lesion, which suggests that this factor may be useful for the treatment of Parkinson's disease.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D009414	Nerve Growth Factors	Factors which enhance the growth potentialities of sensory and sympathetic nerve cells.	Neurite Outgrowth Factor,Neurite Outgrowth Factors,Neuronal Growth-Associated Protein,Neuronotrophic Factor,Neurotrophic Factor,Neurotrophic Factors,Neurotrophin,Neurotrophins,Growth-Associated Proteins, Neuronal,Neuronal Growth-Associated Proteins,Neuronotrophic Factors,Neurotrophic Protein,Neurotrophic Proteins,Proteins, Neuronal Growth-Associated,Factor, Neurite Outgrowth,Factor, Neuronotrophic,Factor, Neurotrophic,Factors, Nerve Growth,Factors, Neurite Outgrowth,Factors, Neuronotrophic,Factors, Neurotrophic,Growth Associated Proteins, Neuronal,Growth-Associated Protein, Neuronal,Neuronal Growth Associated Protein,Neuronal Growth Associated Proteins,Outgrowth Factor, Neurite,Outgrowth Factors, Neurite,Protein, Neuronal Growth-Associated
D009419	Nerve Tissue Proteins		Proteins, Nerve Tissue,Tissue Proteins, Nerve
D009474	Neurons	The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.	Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D003342	Corpus Striatum	Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE.	Lenticular Nucleus,Lentiform Nucleus,Lentiform Nuclei,Nucleus Lentiformis,Lentiformis, Nucleus,Nuclei, Lentiform,Nucleus, Lenticular,Nucleus, Lentiform,Striatum, Corpus
D004298	Dopamine	One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.	Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D006719	Homovanillic Acid	A 3-O-methyl ETHER of (3,4-dihydroxyphenyl)acetic acid.	3-Methoxy-4-Hydroxyphenylacetic Acid,4-Hydroxy-3-Methoxyphenylacetic Acid,3 Methoxy 4 Hydroxyphenylacetic Acid,4 Hydroxy 3 Methoxyphenylacetic Acid,Acid, 3-Methoxy-4-Hydroxyphenylacetic,Acid, 4-Hydroxy-3-Methoxyphenylacetic,Acid, Homovanillic
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001522	Behavior, Animal	The observable response an animal makes to any situation.	Autotomy Animal,Animal Behavior,Animal Behaviors
D013378	Substantia Nigra	The black substance in the ventral midbrain or the nucleus of cells containing the black substance. These cells produce DOPAMINE, an important neurotransmitter in regulation of the sensorimotor system and mood. The dark colored MELANIN is a by-product of dopamine synthesis.	Nigra, Substantia,Nigras, Substantia,Substantia Nigras