Heart failure impairs mood and memory in male rats and down-regulates the expression of numerous genes important for synaptic plasticity in related brain regions

Chronic heart failure (HF) is a serious disorder that afflicts more than 26 million patients worldwide. HF is comorbid with depression, anxiety and memory deficits that have serious implications for quality of life and selfcare in patients who have HF. Still, there are few studies that have assessed the effects of severely reduced ejection fraction (<= 40 %) on cognition in non-human animal models. Moreover, limited information is available regarding the effects of HF on genetic markers of synaptic plasticity in brain areas critical for memory and mood regulation. We induced HF in male rats and tested mood and anxiety (sucrose preference and elevated plus maze) and memory (spontaneous alternation and inhibitory avoidance) and measured the simultaneous expression of 84 synaptic plasticity-associated genes in dorsal (DH) and ventral hippocampus (VH), basolateral (BLA) and central amygdala (CeA) and prefrontal cortex (PFC). We also included the hypothalamic paraventricular nucleus (PVN), which is implicated in neurohumoral activation in HF. Our results show that rats with severely reduced ejection fraction recapitulate behavioral symptoms seen in patients with chronic HF including, increased anxiety and impaired memory in both tasks. HF also downregulated several synaptic-plasticity genes in PFC and PVN, moderate decreases in DH and CeA and minimal effects in BLA and VH. Collectively, these findings identify candidate brain areas and molecular mechanisms underlying HF-induced disturbances in mood and memory.