DEPLETION OF NIGROSTRIATAL AND FOREBRAIN TYROSINE HYDROXYLASE BY S-ADENOSYLMETHIONINE: A MODEL THAT MAY EXPLAIN THE OCCURRENCE OF DEPRESSION IN PARKINSON'S DISEASE
Section snippets
Materials and Methods
Sprague-Dawley male rats weighing 250–350 g (Harlam Labs, OH) were used in the experiments. The rats were acclimatized for about 1 wk in a colony room with 12-h light and 12-h dark cycle. Water and food were supplied ad libitum. Groups of rats were anesthetized by intraperitoneal injection of chloral hydrate (400 mg/kg). A stainless steel guide cannula was stereotaxically placed in the brain for the injection into the lateral ventricle of each rat. The cannula was affixed with dental cement,
Results
Rats injected with 1 μmole of SAM and sacrificed 3 days later had a reduction of tyrosine hydroxylase (TH)-immunoreactivity (IR) in the substantia nigra (SN) (Fig. 1). The depletion was more pronounced (lower intensity) in the SN ipsilateral to the injected ventricle (Fig. 1D), as compared to the contralateral SN (Fig. 1C). Both SNs of the SAM-injected rat (Fig. 1C and D) showed lower TH-IR than the matching SNs of the PBS controls (Fig. 1A and B). A higher magnification of the SN highlighting
Discussion
The results show that SAM depleted TH in the substantia nigra and the caudate nucleus/neostriatum and in fibers located in the frontal cortex or frontal lobe. The reduction of TH-IR in the caudate nucleus (Fig. 4) was moderate as compared to the dramatic reduction of TH-IR in the SN (Fig. 3). The SN projects to the caudate nucleus and SAM damages SN neurons [13], therefore the moderate reduction of TH-IR in the caudate may indicate an increase of TH transport to the nerve terminals, which
Acknowledgements
This work was supported by RR 03020 and by NIH RO1 No. NS28432 and NS31177.
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