Mice Fed Fatty Diets For 30 Weeks Show Signs Of Depression, Anxiety, And Alzheimer's

The cheap, readily available, highly processed food we're consuming too much of is bad for us. An interesting new mouse study has backed up the enduring hypothesis that high fat and sugar diets and cognitive decline such as Alzheimer's are linked.

"Obesity and diabetes impair the central nervous system, exacerbating psychiatric disorders and cognitive decline. We demonstrated this in our study with mice," says University of South Australia neuroscientist and biochemist Larisa Bobrovskaya.

The team were looking for a mouse model that can tell us more about the intersection between Alzheimer's disease, type two diabetes and obesity, and oh boy did they find it.

"It is well known that chronic obesity and type 2 diabetes mellitus are often associated with Alzheimer's disease, along with many other comorbidities, including cardiovascular disease, and renal dysfunction," the team write in their new paper.

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"Moreover, obesity and type 2 diabetes are increasingly linked to impaired central nervous system function, by exacerbating psychiatric and cognitive disorders, including mood disorders, cognitive decline and dementias."

In a world where eating 'badly' is already incorrectly seen as a moral failing, this type of finding isn't likely to help anyone with better eating habits, but it is able to give us more tools to be able to investigate this perplexing link, which the team wanted to look into further in mice.

To find out more, the team looked at adult mice with a mutation in the human tau protein (P301L) called pR5 mice, along with control mice (known as wild type).

In humans, the mutation has been associated with dysfunctions that directly cause the kind of nerve degeneration associated with Alzheimer's. Similarly in mice, the genes provide researchers with a way to precisely identify mechanisms that link dementia with other conditions, such as diabetes.

The two groups were fed either a regular or a high fat diet for 30 weeks. Considering lab mice live for around 1.5 years, this is a pretty decent portion of their life.

The control mice fed a high fat diet put on weight, had an increased risk of exhibiting anxiety-like behaviors, and showed higher levels of tau in the brain. Tau is important because it's a protein which can become hyperphosphorylated into 'tau tangles', which is a biomarker of Alzheimer's.

For those mice with the pR5 mutation fed the high fat diet, there was an even larger slew of problems. They were even more vulnerable to obesity, developed glucose intolerance and insulin resistance, had more depression and anxiety-like behaviors, and their brains showed more tau in the form that causes Alzheimer's.

"Our results show that a high fat diet facilitates the development of peripheral insulin resistance and augments cognitive behavior changes and tau pathology in pR5 transgenic mice," the researchers write.

"The possible consequence of high fat diet-induced pathological changes is ultimately, an aggravation of cognitive deficits in these mice."

This might sound a bit worrying for the 42 percent of adult Americans who are obese, or the 37 million Americans who have type 2 diabetes, but understanding these factors – especially using new mouse models – is helpful for scientists to uncover new treatments or recommend science-backed changes.

"Our findings underline the importance of addressing the global obesity epidemic. A combination of obesity, age and diabetes is very likely to lead to a decline in cognitive abilities, Alzheimer's disease and other mental health disorders," Bobrovskaya says.

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