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Effect of exercise on dopamine neuron survival in prenatally stressed rats

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Abstract

Prenatal stress has been associated with increased vulnerability to psychiatric disturbances including schizophrenia, depression, attention-deficit hyperactivity disorder and autism. Elevated maternal circulating stress hormones alter development of neural circuits in the fetal brain and cause long-term changes in behaviour. The aim of the present study was to investigate whether mild prenatal stress increases the vulnerability of dopamine neurons in adulthood. A low dose of 6-hydroxydopamine (6-OHDA, 5 µg/4 µl saline) was unilaterally infused into the medial forebrain bundle of nerve fibres in the rat brain in order to create a partial lesion of dopamine neurons which was sufficient to cause subtle behavioural deficits associated with early onset of Parkinson’s disease without complete destruction of dopamine neurons. Voluntary exercise appeared to have a neuroprotective effect resulting in an improvement in motor control and decreased asymmetry in the use of left and right forelimbs to explore a novel environment as well as decreased asymmetry of tyrosine hydroxylase-positive cells in the substantia nigra pars compacta and decreased dopamine cell loss in 6-OHDA-lesioned rats. Prenatal stress appeared to enhance the toxic effect of 6-OHDA possibly by reducing the compensatory adaptations to exercise.

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Acknowledgements

This work was supported by the University of Cape Town and the National Institutes of Health (NIH) Fogarty International Center grants R21DA018087 & R01TW008040 to Michael J. Zigmond, principal investigator. The authors wish to express their thanks to Ms Shula Johnson for technical support and to Dr Michael Zigmond, Dr Amanda Smith and Ms Sandy Castro for their invaluable advice and training provided for Dr Musa Mabandla. This work forms part of the PhD thesis of Dr Musa Mabandla.

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Correspondence to Vivienne A. Russell.

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Mabandla, M.V., Kellaway, L.A., Daniels, W.M.U. et al. Effect of exercise on dopamine neuron survival in prenatally stressed rats. Metab Brain Dis 24, 525–539 (2009). https://doi.org/10.1007/s11011-009-9161-6

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