The Link Between a High Salt Diet and Impaired Brain Function in Mice

What's the science?

A diet high in salt has been linked to altered brain blood supply, stroke and cognitive impairment. Evidence suggests that the immune system becomes activated in response to salt, and may be involved. Recently in Nature Neuroscience, Faraco and colleagues report a mechanism linking salt in the gut to immune system activation and reduced blood flow in the brain.

How did they do it?

They fed mice high salt diets and measured immune system markers in the blood and the function of cells lining brain blood vessels (endothelial cells which work to allow blood flow) at set time intervals over a 24 week period. They also measured resting brain blood flow using magnetic resonance imaging (MRI) with arterial spin labelling.

What did they find?

Mice fed a high salt diet had lower brain blood flow and dysfunctional endothelial cells. Additionally, they had worsened memory function, and a reduced ability to perform daily activities. Mice fed a high salt diet also had higher levels of immune cells (lymphocytes) in the gut, which resulted in higher inflammatory markers (IL-17) in the blood. Importantly, the lowered brain blood flow and cognitive problems were dependent on this immune system response.

What's the impact?

This study confirms previous theories that the immune system plays a role in linking dietary salt with brain function. Importantly, it reveals a specific immune system pathway linking the gut and the brain. This gut-brain pathway could be targeted with therapies to prevent harmful effects of salt on the brain. 

G. Faraco et al., Dietary salt promotes neurovascular and cognitive dysfunction through a gut-initiated TH17 response. Nat. Neurosci. (2018)

Access the original scientific publication here.

Amyloid-β Proteins Differ Between Alzheimer’s Disease Subtypes

What’s the science?

Alzheimer’s disease can be genetically inherited (familial/heritable) or sporadic. A key feature of the disease is the build up of amyloid-β proteins in the brain. A mutant form of amyloid-β is found in heritable Alzheimer’s disease, and is thought to cause the misfolding of normal amyloid-β proteins, leading to a more rapid build up. Recently in PNAS, Condello and colleagues probed the structure of different conformations or strains of amyloid-β proteins, to see whether they differ between heritable and sporadic Alzheimer’s.

How did they do it?

They performed confocal spectral imaging using three fluorescent dyes that bind to amyloid protein and are sensitive to protein structure in mouse and human brains. Different dyes bind differently to distinct protein conformations. In mice, they combined mutated and non-mutated amyloid-β, to test whether the mutated form could cause protein misfolding.

What did they find?

The heritable and sporadic amyloid-β plaques exhibited different fluorescence intensities after staining with the three dyes, meaning they could be differentiated. The fluorescence emission spectra also differed between disease types, suggesting different protein conformations. In mice, when mutated and non-mutated amyloid-β were mixed, the mutated amyloid-β acted as a template allowing the normal amyloid-β to misfold.

What’s the impact?

This is the first study to use this fluorescence microscopy technique to assess different strains of amyloid-β. The different protein structure in these amyloid-β strains could help to explain differences in the rate of disease progression, for example between familial Alzheimer’s disease compared to sporadic Alzheimer’s disease. Understanding the differences in protein structure between these amyloid strains may help clarify how they cause other proteins to misfold and the disease to spread.

C. Condello et al., Structural heterogeneity and intersubject variability of Aβ in familial and sporadic Alzheimer’s disease. PNAS. 115(4) (2018).

Access the original scientific publication here.

Your Brain is Right on Time

What's the science?

Everyday we need to speak and move at different speeds depending on the situation, but the way we control the timing of our speech and movements is not well understood. This week in Nature Neuroscience, Wang and colleagues report a new mechanism in the brain for controlling how we time things in a flexible way. 

How did they do it?

They performed an experiment where monkeys were trained to flexibly make movements after both short and long time intervals. They recorded the rate of neuron firing during this time using electrodes in two brain regions known to be involved in brain timing: the medial frontal cortex and the caudate.

What did they find?

They demonstrate that in both of these regions, the longer the time interval before the monkey's movement, the slower the neuron firing rate. This means that the speed of neuron firing is scaled according to the time interval. In other words, the brain has a mechanism for adjusting its firing rate so that movements can stay flexible. This scaling of neuron firing explained both the timing and flexibility of the monkey's movements. 

What's the impact?

This is the first study to clarify the mechanism through which the brain controls timing of movements. Previous models of timing didn't quite fit with the data recorded from the brain. Now we have a better understanding of how we can play music, speak at different speeds and move when we want to.
 

Read the original journal article here.

J. Wang, D. Narain, E. A. Hosseini, M. Jazayeri, Flexible timing by temporal scaling of cortical responses. Nat. Neurosci. 21, 102–110 (2017).

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