High-fat diet and aging interact to produce neuroinflammation and impair hippocampal- and amygdalar-dependent memory

Abstract

More Americans are consuming diets higher in saturated fats and refined sugars than ever before, and based on increasing obesity rates, this is a growing trend among older adults as well. While high saturated fat diet (HFD) consumption has been shown to sensitize the inflammatory response to a subsequent immune challenge in young adult rats, the inflammatory effect of HFD in the already-vulnerable aging brain has not yet been assessed. Here, we explored whether short-term (3 days) consumption of HFD would serve as a neuroinflammatory trigger in aging animals, leading to cognitive deficits. HFD impaired long-term contextual (hippocampal-dependent) and auditory-cued fear (amygdalar-dependent) memory in aged, but not young adult rats. Short-term memory performance for both tasks was intact, suggesting that HFD impairs memory consolidation processes. Microglial markers of activation Iba1 and cd11b were only increased in the aged rats, while MHCII was further amplified by HFD. Furthermore, these HFD-induced long-term memory impairments were accompanied by IL-1β protein increases in both hippocampus and amygdala in aged rats. Central administration of IL-1RA in aged rats following conditioning mitigated both contextual and auditory-cued fear memory impairments caused by HFD, strongly suggesting that IL-1β plays a critical role in these effects. Voluntary wheel running, known to have anti-inflammatory effects in the hippocampus, rescued hippocampal-dependent but not amygdalar-dependent memory impairments caused by HFD. Together, these data suggest that short-term consumption of HFD can lead to memory deficits and significant brain inflammation in the aged animal, and strongly suggest that appropriate diet is crucial for cognitive health.

Dysfunctional cerebrovascular tone contributes to cognitive impairment in a non-obese rat model of prediabetic challenge: Role of suppression of autophagy and modulation by anti-diabetic drugs

“…On the one hand, MHC-fed rats showed increased expression of CD68 and IBA-1, both markers of microglial activation associated with chronic neuroinflammation(72), in the CA1 area of the hippocampus. On the other hand, increased apoptotic changes in MHC-fed rat hippocampus appeared as increased TUNEL staining and higher caspase-3 activity.Similar observations are common in recent literature whereby neuroinflammation and microglial activation(73)(74)(75), together with hippocampal apoptosis(76,77), occur in association with high fat diet-induced cognitive decline. The previous studies provided observational evidence for the aforementioned association.…”

TLR4 inhibitor TAK-242 attenuates the adverse neural effects of diet-induced obesity

“…The age at which rodents are exposed to diet-induced obesity may be a factor. For example, one study found significant effects of HFD on behavior in mice started on diet at 5 weeks of age, but not in animals started at 8 weeks [ 129 ], whereas another found behavioral impairments in response to HFD in aged but not young adult rats [ 130 ]. These studies suggest that the age at which exposure to HFD occurs may be important in determining whether behavioral deficits are observed.…”

Improving Effects of Hop-Derived Bitter Acids in Beer on Cognitive Functions: A New Strategy for Vagus Nerve Stimulation

“…Obesity or excess body weight negatively correlates with cognitive function and with the volume of several brain regions including hippocampus [20,21]. In animal studies, high fat diet feeding induces neuroinflammation, which leads to the cognitive decline [22]. These findings suggest that preventing type II diabetes and obesity would be effective approaches in dementia prevention.…”