Soluble betaamyloid(1-42): a critical player in producing behavioural and biochemical changes evoking depressive-related state?

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 bamyloid (Ab). Thus, we investigated the effects of soluble Ab1-42 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 Ab1-42 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: Ab1-42 did not affect the ability to distinguish between familiar and novel objects, but Ab-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, Ab-injected rats exhibited a selective reduction in 5-HT content, BDNF and NGF expression. Conclusions and implications: Our data suggest that soluble Ab-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 Ab might be sensitive indicators of early phases of AD and possible risk factors for the expression of neuropsychiatric symptoms in AD.