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Behavioral effects of persistent lymphocytic choriomeningitis virus infection in mice
1Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037.
Abstract:
Lymphocytic choriomeningitis virus (LCMV) is a nonlytic murine virus that provides a valuable model system for studying the behavioral correlates of CNS viral infection. Newborn or immunosuppressed mice infected with LCMV develop a persistent tolerant infection characterized by continuous viral production. Virus can be found in various body organs including lung, liver, kidney, and brain. In brain, neurons are the predominant CNS cells infected and the greatest number of persistently infected neurons are found in the cerebral cortex, hippocampus, other limbic structures and parts of the hypothalamus. Despite continuous infection throughout the animal's life, neurons show no structural injury or dropout. Mice from the DBA/2J strain were infected with LCMV (1000 plaque-forming units) within 18 h of birth and tested for behavioral function as adults. Plaque assays indicated persistent infection in virus-injected mice. Mice were tested for their ability to learn a Y-maze spatial discrimination to avoid the onset of a mild footshock (0.43 mA). The number of correct avoidance responses made during training was taken as a measure of acquisition performance. The virus-infected mice showed a deficit in acquisition of the Y-maze discrimination compared to that seen in vehicle-injected and noninjected controls. Following additional training to reach control levels of performance, the infected mice and the controls were injected with the cholinergic antagonist scopolamine. Scopolamine (2.0 mg/kg) disrupted the performance of the infected mice significantly more than control performance, suggesting that a cholinergic dysfunction accounted for some of the learning deficit. A separate group of virus-infected mice exhibited hypoactivity during the first exposure to a locomotor testing apparatus.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Lymphocytic choriomeningitis virus (LCMV) infection in newborn mice causes persistent brain infection and learning deficits. This viral CNS infection impairs spatial learning and may involve cholinergic dysfunction.
Area of Science:
- Neuroscience
- Virology
- Behavioral Science
Background:
- Lymphocytic choriomeningitis virus (LCMV) establishes persistent, non-lytic infections in the central nervous system (CNS).
- Neurons, particularly in the cerebral cortex and hippocampus, are the primary CNS cells infected by LCMV.
- Despite persistent viral presence, infected neurons show no structural damage or loss.
Purpose of the Study:
- To investigate the behavioral consequences of persistent LCMV infection in the CNS.
- To assess learning and memory deficits in LCMV-infected mice.
- To explore the role of cholinergic systems in LCMV-induced behavioral impairments.
Main Methods:
- Newborn DBA/2J mice were infected with LCMV and tested as adults for behavioral function.
- Y-maze spatial discrimination task was used to measure learning acquisition.
- Plaque assays confirmed persistent viral infection.
- Scopolamine, a cholinergic antagonist, was administered to assess its effect on performance.
- Locomotor activity was measured in a separate cohort of infected mice.
Main Results:
- LCMV-infected mice exhibited significant deficits in acquiring the Y-maze spatial discrimination task.
- Scopolamine administration more severely disrupted the performance of infected mice compared to controls.
- Infected mice showed hypoactivity during initial exposure to a locomotor testing apparatus.
Conclusions:
- Persistent LCMV infection in the CNS leads to deficits in learning and memory.
- Cholinergic dysfunction likely contributes to the observed learning impairments.
- LCMV infection in mice serves as a valuable model for studying CNS viral infections and their behavioral effects.