Unilateral lesions of the Nigrostriatal pathway

Hsuan L.

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Unilateral lesions of the Nigrostriatal pathway

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Abstract

The nigrostriatal system through the basal ganglia is essential for regulating motor movement. Normal motor behavior requires a delicate balance between the excitatory direct pathway and the inhibitory indirect pathway modulated by the D1 and D2 receptors, respectively. Unilateral destruction of the striatum or its dopaminergic inputs changes unidirectional behavior in animals. The most common method of inducing a unilateral lesion is through the injection of the neurotoxin 6-OHDA in substantia nigra pars compacta (SNc). This lesion causes a lateralized destruction of dopamine neurons as well as a loss of striatal dopamine innervation. The anatomical and behavioral effects of amphetamine and apomorphine were examined to investigate the role of dopamine neurons in the nigrostriatal pathway. Amphetamine induced net ipsiversive rotations while apomorphine induced net contraversive rotation with increasing time after 6-OHDA lesions. The role of lesion size has contributed substantially to the rotational behavior of both drugs. Furthermore, behavioral effects of this lesion are similar to motor symptoms and neuropathology seen in patients with Parkinson's Disease. Hence, the 6-OHDA lesion may be a relevant model for finding the treatment of Parkinson's disease.

Abstract.
Introduction.
Materials and methods.
1. Animals.
2. Surgery.
Behavioral testing.
1. Preoperative testing.
2. Postoperative testing.
Histology.
1. Intracardial perfusion.
2. Sectioning and staining.
3. Anatomical analysis.
Statistical analysis.
1. Behavioral analysis.
2. Anatomical analysis.
Pargyline versus no Pargyline-injected group.
Correlation between percentage of cell loss and rotational behavior.
Discussion.
Role of lesion size.
Conclusion.

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[...] In experimental animals, the total number of rotations was five times greater post-amphetamine injection than pre-injection 4.049 Similarly, in control rats the total number of rotations was three times greater post-amphetamine injection than pre-injection 2.530 After establishing the baseline response to amphetamine, experimental rats with unilateral 6-OHDA lesions developed significant ipsilateral rotation bias 6-7 days as well as 10-11 days post-surgery following amphetamine injection, while the control group showed no variation in net ipsiversive rotations pre- and post-operatively (Figure 5). [...]

[...] Furthermore, studies have shown that a unilateral lesion of the nigrostriatal pathway induces postural asymmetry (Ungerstedt, 1971). The role of dopamine neurons and the effect of 6-OHDA lesions in SNc have been investigated with respect to rotational behavior under amphetamine and apomorphine. The effect of these drugs, however, varied depending on the placement and the extent of the lesion produced. Results from other studies have suggested that 6-OHDA injected into the SN pars compacta can effectively induce lesions to DA neurons (Fornaguera et al., 1994). [...]

[...] Histology The Nissl stain was used to determine the completeness of 6-OHDA lesions of the nigrostriatal pathway. We found that the experimental group had a significantly greater percentage of cell loss in SNc than the control group. This present study has shown that injection of 6-OHDA into the SNc selectively destroys DA neurons. Rotational behavior under amphetamine In the present study, we have demonstrated that amphetamine increases motor output and have determined the animals' preferred direction of rotation under amphetamine. [...]

[...] However, the difference was due to a significant increase of total rotation number in post-injection compared to pre-injection in the experimental group 2.146 ) as well as in the control group 2.164 Having the baseline response to apomorphine, animals with unilateral 6-OHDA lesions showed a marked contralatral rotation bias 13 days post-surgery, but the control rats did not show a significant change in the number of net contraversive rotations pre- and post-operatively (Figure 8). A two-way analysis showed that there was not a significant main effect of net contraversive rotations between control versus lesioned groups, timeframe relative to the surgical day, and interaction between these two variables. [...]

[...] Unilateral lesions of the Nigrostriatal pathway ABSTRACT The nigrostriatal system through the basal ganglia is essential for regulating motor movement. Normal motor behavior requires a delicate balance between the excitatory direct pathway and the inhibitory indirect pathway modulated by the D1 and D2 receptors, respectively. Unilateral destruction of the striatum or its dopaminergic inputs changes unidirectional behavior in animals. The most common method of inducing a unilateral lesion is through the injection of the neurotoxin 6-OHDA in substantia nigra pars compacta (SNc). [...]

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