Eunju Shin

Tel: +46 46 222 05 55 Fax: +46 46 222 05 59 E-mail: Eunju.Shin@med.lu.se

Research interests

Parkinson’s disease (PD) is a neurodegenerative disease associated with a profound loss of the dopaminergic (DA) neurons in the substantia nigra (SN); therefore, current therapeutic strategies are focused on restoration of DA neurotransmission or DA neuron replacement. However, studies of postmortem PD brains have shown that not only DA neurons in the SN but also the norepinephrine (NE) neurons in the locus ceruleus (LC) degenerate, and that the NE neurodegeneration may be as profound, and also precedes degeneration of the midbrain DA neurons. The early involvement of the NE system is also in line with the caudal-to-rostral disease progression predicted by the model proposed by Braak et al.

We propose that the degeneration of the LC will contribute importantly both to the severity and progression of motor symptoms in PD patients. In the present project we propose to test this hypothesis in two alternative and complementary models of PD: the standard 6-OHDA lesion model, and a more recently introduced ?-synuclein model of PD, induced by overexpression of human ?-synuclein in the SN. In the latter model, which has been developed in the Lund laboratory over the last few years, a recombinant adeno-associated viral (AAV) vector containing human ?-synuclein is injected into the SN in adult rats. Using this approach Kirik et al. have shown that the nigral DA neurons undergo progressive degenerative changes and cell loss, accompanied by behavioural impairments. However, similar to what has been observed in the MPTP-induced model, the cell loss is variable, the behavioural changes are modest, and the treated rats slowly recover from the toxic effect of ?-synuclein inclusions.

We are also exploring the role of the NE system in the induction of L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia. Clinically, the dopamine precursor, L-DOPA has been the most common and successful drug to treat the symptoms of PD. However, prolonged administration of L-DOPA produces uncontrolled excessive movement called dyskinesia. L-DOPA administration in DA-depleted animals also generates dyskinesia. Furthermore, a study has shown that dopamine ?-hydroxylase knockout mice (Dbh-/-, lacks NE production) are more prone to develop dyskinesia than MPTP-treated mice, and restoration of NE could reverse some degree of dyskinesia. Dual lesioned (DA and NE depleted) rats also have shown constantly higher levels of dyskinesia than DA depleted rats measured by the abnormal involuntary movement scale (AIMS). However, some other studies have shown that there was no difference in dyskinetic development between DA-depleted and DA- and NE-depleted animals. Taken together, these studies underline an important role of the NE system in modulating the dyskinetic response to L-DOPA in DA-deficient animals.

• Curriculum Vitae
• Complete list of publications

Visiting address:
Neurobiology Unit
BMC House A Floor 11
(see further details on Visit us)

Mailing address:
Neurobiology Unit, BMC A11
Department of Experimental Medical Science
Lund University
221 84 Lund, Sweden

Print version Tell a friend about this page