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Stereotaxic microinjection of HSV-1 selectively decreases striatal dopamine concentrations in mice
1Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany 12201.
Abstract:
BALB/c mice were stereotaxically injected in the striatum with either the MP or MacIntyre strain of herpes simplex type 1. Three days later, at a time when the animals were free from overt signs of infection, they were killed by cervical dislocation and the striatum was rapidly removed. Concentrations of dopamine, norepinephrine, serotonin and their metabolites were subsequently determined by means of high-performance liquid chromatography with electrochemical detection. With both strains of virus, dopamine levels were reduced and the ratio of homovanillic acid to dopamine was elevated in MP-inoculated mice. Norepinephrine, serotonin and its metabolites were unaffected. Immunoperoxidase staining in separate, identically treated animals indicated that the infection was confined to the striatum and necrosis was minimal at this point in time. These results demonstrate that dopamine metabolism can be affected by herpes simplex in the absence of immunocytochemical evidence of infection of the cell bodies of dopaminergic neurons or cellular death.
Insights
Herpes simplex virus type 1 infection in mice reduced dopamine levels in the striatum. This viral effect on dopamine metabolism occurred without significant cell damage or infection of dopaminergic neurons.
Area of Science:
- Neuroscience
- Virology
- Biochemistry
Background:
- Herpes simplex virus (HSV) can cause neurological complications.
- The impact of HSV on neurotransmitter systems, particularly dopamine, is not fully understood.
Purpose of the Study:
- To investigate the effect of HSV type 1 infection on dopamine metabolism in the mouse striatum.
- To determine if HSV infection alters norepinephrine and serotonin levels.
Main Methods:
- BALB/c mice were stereotaxically injected with HSV-1 (MP or MacIntyre strain) in the striatum.
- Neurotransmitter and metabolite concentrations (dopamine, norepinephrine, serotonin) were measured using high-performance liquid chromatography with electrochemical detection.
- Immunoperoxidase staining was used to assess viral spread and neuronal damage.
Main Results:
- HSV-1 infection led to reduced dopamine levels and an elevated homovanillic acid to dopamine ratio in the striatum.
- Norepinephrine and serotonin levels, along with their metabolites, remained unaffected by the infection.
- Viral infection was confined to the striatum with minimal necrosis observed at three days post-infection.
Conclusions:
- Herpes simplex virus type 1 can alter dopamine metabolism in the striatum.
- These metabolic changes occur early in infection, preceding significant neuronal damage or detectable infection of dopaminergic neuron cell bodies.