University of Hertfordshire

Dopamine neurons in rat substantia nigra revealed by tyrosine hydroxylase immunohistochemistry

Area of research:

Behavioural therapies for protecting dopamine neurons in a lesion model of Parkinson’s disease

Current research funded by the Parkinson’s Disease Society, UK, is exploring the possibility that physical activity may be neuroprotective and spare dopamine neurons that would otherwise die following a neurotoxic insult in a rat model of Parkinson’s disease. The main hypothesis is that activity will reduce the impact of 6-hydroxydopamine (6OHDA) lesions both anatomically, protecting dopamine neurons that would otherwise be destroyed by the toxin, and functionally, sparing behaviours that would otherwise be impaired as a consequence of the dopamine loss. The research may benefit people living with Parkinson’s disease by determining whether behavioural therapies and exercise regimes have the potential to counter the ongoing disease process by slowing the degeneration of dopamine neurons.

Forced use of a limb during the period immediately following a 6OHDA lesion of the substantia nigra has been reported to protect dopamine levels in the striatum contralateral to the limb (Tillerson et al., 2001). The present project is investigating whether the neuroprotective effect of activity shown in this particular case also applies in a variety of situations that may be more relevant to people with Parkinson’s disease. Activity is manipulated by training on tasks on which responses are required on one side only, by housing in enriched environments and by treating with stimulant drugs such as amphetamine and L-Dopa, and by combinations of drugs and task induced physical activity. The extent of the lesion is determined using tyrosine hydroxylase immunohistochemistry to reveal dopamine neurons in the substantia nigra and High Performance Liquid Chromatography (HPLC) to measure dopamine levels in the striatum. The HPLC analysis in this project benefits from techniques developed for monoamine analysis in concurrent projects investigating cannabinoid-dopamine interactions

Using a task in which rats retrieved food from pots placed to one side of the body, we have found sparing of dopamine neurons in the substantia nigra and dopamine levels in the striatum of rats that made responses on the contralateral side (top figure) compared with rats that made responses on the ipsilateral side (bottom figure) relative to a 6OHDA lesion. The results suggest that physical activity may lessen the impact of a dopamine lesion, whereas inactivity may make the lesion worse.

Link to abstract

"Behavioral activity directed into contralateral space spares dopamine neurons following a unilateral 6-hydroxydopamine lesion of the medial forebrain bundle in rats” presented at the Society for Neuroscience meeting, Atlanta, USA, October 2006: