Behavioural deficits and serotonin depletion in adult rats after transient infant nasal viral infection.
Dysfunction of subcortical serotoninergic neurons has been implicated in some behaviour disturbances. The serotoninergic neurons in the dorsal and median raphe project widely in the brain. They innervate the olfactory bulbs and can be targets for exogenous agents attacking the olfactory epithelium and bulbs. We report here an injury to the serotoninergic neurons after intranasal infection in 12-day-old rats with a temperature-sensitive mutant of vesicular stomatitis virus. The brain infection was focal and transient. Viral antigens could no longer be detected 13-15 days after infection. In spite of this the animals, as adults, had a severe serotonin depletion in the cerebral cortex and hippocampus, and showed abnormal locomotor and explorative behaviour as well as learning deficits. The neocortex was histologically intact and parameters related to other neurotransmitters such as dopamine, noradrenaline, GABA and acetylcholine showed no marked changes. A relatively selective damage to serotoninergic nuclei as a result of virus neuroinvasion through a natural portal of entry, may constitute a new pathogenetic mechanism for cortical dysfunction and behavioural deficits.
Department of Geriatric Medicine, Karolinska Institute, Huddinge Hospital, Sweden.
A K
AK
Mohammed
O
O
Magnusson
J
J
Maehlen
F
F
Fonnum
E
E
Norrby
M
M
Schultzberg
K
K
Kristensson
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000503:physiopathology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003071:Cognition; D004298:Dopamine / Q000378:metabolism; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D009043:Motor Activity; D009154:Mutation; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics; D014777:Virus Diseases / Q000503:physiopathology / Q000523:psychology*
D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid