부산대학교 도서관

Background and purpose: 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 βamyloid (Aβ). Thus, we investigated the effects of soluble Aβ1-42 on working memory and depressive/anxiety-related behaviour in rats and on 5-hydroxytryptaminergic neurotransmission and neurotrophin content in various brain regions. Experimental approach: 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 Aβ1-42 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). Key results: Aβ1-42 did not affect the ability to distinguish between familiar and novel objects, but Aβ-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, Aβ-injected rats exhibited a selective reduction in 5-HT content, BDNF and NGF expression. Conclusions and implications: Our data suggest that soluble Aβ-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 Aβ might be sensitive indicators of early phases of AD and possible risk factors for the expression of neuropsychiatric symptoms in AD. [ABSTRACT FROM AUTHOR]