Soluble beta amyloid(1-42): a critical player in producing behavioural and biochemical changes evoking depressive-related state?
OBJECTIVE
Depression is common in early phases of Alzheimer's disease (AD) and may represent prodromal symptoms of dementia. Recent reports suggest that early memory deficits and neuropsychiatric symptoms are caused by soluble rather than aggregated betaamyloid (Abeta). Thus, we investigated the effects of soluble Abeta(1-42) on working memory and depressive/anxiety-related behaviour in rats and on 5-hydroxytryptaminergic neurotransmission and neurotrophin content in various brain regions.


METHODS
Behavioural reactivity to novel object recognition, open field, elevated plus maze and forced swimming test were assessed 7 days after i.c.v. injection of Abeta(1-42) or its vehicle. BDNF (brain-derived neurotrophic factor) and NGF (nerve growth factor) mRNA and protein levels and 5-hydroxytriptamine (5-HT) content were measured in the prefrontal cortex (PFC), striatum (STR) and nucleus accumbens (NAc).


RESULTS
Abeta(1-42) did not affect the ability to distinguish between familiar and novel objects, but Abeta-treated rats exhibited an increase in forced swimming immobility. No differences were revealed between experimental groups in the elevated plus maze test or in self-grooming (evaluated in the open field). In the PFC, but not STR or NAc, Abeta-injected rats exhibited a selective reduction in 5-HT content, BDNF and NGF expression.


CONCLUSIONS
Our data suggest that soluble Abeta-treated rats have a depressive, but not anxiogenic-like, profile, accompanied by brain region-dependent alterations in the expression of neurotrophins and 5-hydroxytryptaminergic neurotransmission. Hence, these alterations induced by soluble Abeta might be sensitive indicators of early phases of AD and possible risk factors for the expression of neuropsychiatric symptoms in AD.
Colaianna
M
M
Department of Biomedical Sciences, University of Foggia, Italy.
Tucci
P
P
Zotti
M
M
Morgese
M G
MG
Schiavone
S
S
Govoni
S
S
Cuomo
V
V
Trabace
L
L
D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D001522:Behavior, Animal / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers; D003863:Depression / Q000139:chemically induced*; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism
D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; D017931:DNA Primers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D012701:Serotonin; D020932:Nerve Growth Factor