Neuroprotection in the rat Parkinson model by intrastriatal GDNF gene transfer using a lentiviral vector.

• We used a recombinant lentiviral vector (rLV) for gene delivery of GDNF to the striatum, and assessed its neuroprotective effects in the intrastriatal 6-hydroxydopamine (6-OHDA) lesion model.The level of GDNF expression obtained with the rLV-GDNF vector was dose-related and ranged between 0.9-9.3 ng/mg tissue in the transduced striatum, as determined by ELISA, and 0.2-3.0 ng/mg tissue were detected in the ipsilateral substantia nigra (SN), due to anterograde transport of the GDNF protein. GDNF expression was apparent at 4 days and maintained for > 8 months after injection. Striatal delivery of rLV-GDNF efficiently protected the nigral dopamine (DA) neurons and their projection, against the 6-OHDA lesion (65-77% of intact side). Sprouting of the lesioned axons was observed along the nigrostriatal pathway, precisely corresponding to the areas containing anterogradely transported GDNF.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Nyckelord

Lentivirus : genetics

Luminescent Proteins : pharmacokinetics

Motor Activity : drug effects

Nerve Tissue Proteins : genetics

Nerve Tissue Proteins : pharmacokinetics

Nerve Tissue Proteins : therapeutic use

Neurons : drug effects

Neurons : metabolism

Neuroprotective Agents : therapeutic use

Oxidopamine : pharmacology

Parkinson Disease : pathology

Parkinson Disease : physiopathology

Parkinson Disease : therapy

Rats

Sprague-Dawley

Substantia Nigra : drug effects

Substantia Nigra : pathology

Support

Non-U.S. Gov't

Tyrosine 3-Monooxygenase : metabolism

Indicators and Reagents : pharmacokinetics

Genetic Vectors

Gene Transfer Techniques

Female

Dopamine : metabolism

Corpus Striatum : pathology

Corpus Striatum : drug effects

Animal

Publikations- och innehållstyp

art (ämneskategori)

ref (ämneskategori)