Voluntary exercise reduces the neurotoxic effects of 6-hydroxydopamine in maternally separated rats

Abstract

Maternal separation has been associated with development of anxiety-like behaviour and learning impairments in adult rats. This has been linked to changes in brain morphology observed after exposure to high levels of circulating glucocorticoids during the stress-hyporesponsive period (P4 to P14). In the present study, adult rats that had been subjected to maternal separation (180 min/day for 14 days) during the stress-hyporesponsive period, received unilateral infusions of a small dose of 6-hydroxydopamine (6-OHDA, 5 μg/4 μl saline) into the medial forebrain bundle. The results showed that voluntary exercise had a neuroprotective effect in both non-stressed and maternally separated rats in that there was a decrease in forelimb akinesia (step test) and limb use asymmetry (cylinder test). Maternal separation increased forelimb akinesia and forelimb use asymmetry and reduced the beneficial effect of exercise on forelimb akinesia. It also reduced exploratory behaviour, consistent with anxiety-like behaviour normally associated with maternal separation. Exercise appeared to reduce dopamine neuron destruction in the lesioned substantia nigra when expressed as a percentage of the non-lesioned hemisphere. However, this appeared to be due to a compensatory decrease in completely stained tyrosine hydroxylase positive neurons in the contralateral, non-lesioned substantia nigra. In agreement with reports that maternal separation increases the 6-OHDA-induced loss of dopamine terminals in the striatum, there was a small increase in dopamine neuron destruction when expressed as a percentage of the non-lesioned hemisphere but there was no difference in dopamine cell number, suggesting that exposure to maternal separation did not exacerbate dopamine cell loss.

Early use of oleanolic acid provides protection against 6-hydroxydopamine induced dopamine neurodegeneration

“…This is in support of existing literature suggesting that 6-OHDA elicits selective destruction of dopamine neurons, thus mimicking the human condition in rodents (Martıé t al., 2002;Mabandla and Russell, 2010). We also showed that oleanolic acid treatment attenuated the effect of the neurotoxin 6-OHDA on dopamine neurons when given 7 days and 1 day post-lesion.…”

“…The limb-use asymmetry (cylinder) test was used to assess explorative behavior of the rat placed in a transparent cylinder (20 cm diameter and 30 cm height) and videotaped for a period of 5 min (Tillerson et al, 2002;Mabandla, 2010). The cylinder test assesses the use of one or both forelimbs for vertical exploration and landing (Cenci, 2002).…”

“…The forelimb akinesia (step) test was used to investigate movement initiation (Schallert et al, 1992;Mabandla, 2010). Each animal was held above the table by its torso with its hindquarters raised such that the rat's body weight was supported by the forelimb being tested.…”

Stress, depression and Parkinson's disease

“…Maternal care disruption can have other long-term effects, such as the appearance of depressive symptoms in adult animals (Matthews and Robbins, 2003). Conversely, exercise can be neuroprotective in PD in both basic and clinical studies (Mabandla et al, 2010). Rats subjected to maternal separation during the neonatal stress hyporesponsive period of development and later allowed to voluntarily exercise showed reduced forelimb akinesia and forelimb-use asymmetry compared to non-exercised rats (Mabandla et al, 2010).…”

The neuroprotective effects of voluntary exercise in a restraint stress model

“…Physical activity increases the number of new cells and improves performance in learning 24 . Exercise also appears to protect neurons from destruction in the substantia nigra of maternally separated rat pups 25 . However, the protective effects of voluntary exercise on cell formation in the striatum have not yet been investigated.…”