Tag Archives: hippocampus

Study Shows How Alzheimer’s Affects Men’s and Women’s Brains Differently

Women are around twice as likely to develop Alzheimer’s disease during their lifetimes compared to men. This effect is also seen in mouse models of the disease. When mice are genetically engineered to developed Alzheimer’s, the female mice tend to have an earlier diseae onset and more severe pathology compared to hte male mice. The reasons for this discrepancy are unknown. However, a recent study published in Neurobiology of Aging attempted to shed some light on the mystery.

The researchers were interested in studying adult neurogenesis, which is our brains’ ability to create new neurons throughout our lives. Neurogenesis primarily occurs in two areas of the brain: the olfactory bulb, which is involved with the sense of smell, and the hippocampus, which is important for memory. In this study, the scientists wanted to figure out whether neurogenesis in the hippocampus was different for male and female mice with Alzheimer’s disease.

First, they subjected the mice to a test designed to test spatial memory, which is particularly important for the hippocampus. They placed the mice in a container with two objects and allowed them to explore for a few minutes. The next day, they placed the mice back in the container, but now one of the objects had been moved to a new location. We would expect the mice to spend more time sniffing and investigating the object that had been moved, and less time sniffing the object that was in the same place as before.

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When one of the cups is moved to a new location, the mouse should spend more time sniffing it compared to the cup that wasn’t moved. This test is used to analyze the mouse’s spatial memory. Image Source

The result was interesting. While the male mice had no trouble rembering which cup had been moved, the female mice did significantly worse, spending the same amount of time sniffing both of the cups. This suggested that the female mice might have some impairment in their spatial memory.

Next, the researches looked at the mice’s brains. They used a technique that caused all newly-born neurons to be labeled bright green, and counted how many neurons were born in the hippocampus during a two-week period. The male mice produced more than four times as many neurons as the female mice. Conversely, the female mice had nearly twice as many astrocytes in their hippocampi compared to the males. Astrocytes are another type of brain cell that is often associated with inflammation. These results suggested that the female mice’s brains were producing many astrocytes but few neurons, perhaps contributing to their impaired spatial memory.

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This image from the paper shows astrocytes labeled in red. In the top right panel, you can see that the female Alzheimer’s (APP/PS1) mice have far more red area than the males, indicating a greater number of astrocytes.

The results of this study suggest that the brains of female mice with Alzheimer’s may be devoting so many resources to creating new astrocytes that there’s not enough left to create neurons. However, it opens up many new questions. What is causing this overproliferation of astrocytes in the female mice? The authors of the paper suggest estrogen as a possible cause, since this hormone has been shown to influence memory. Additional studies are needed to determine the true cause.

 

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Alzheimer’s Patients May Experience “Silent Seizures”

If you’ve read our recent article on sleep science, you know that neurons release amyloid-beta (a toxic protein implicated in Alzheimer’s disease) during periods of activity. The protein is excreted as a waste product whenever neurons fire an electrical signal. This is probably why patients with epilepsy often have large amyloid-beta plaques in their brains, as the fast pulses of activity created by seizures cause neurons to excrete large amounts of the protein. Based on this observation, some have theorized that the buildup of amyloid-beta in Alzheimer’s disease could be caused by hyperactive neurons.

In a paper published recently in Nature Medicine, researchers used electrodes to monitor neuronal activity in the medial temporal lobe (MTL) of two patients with early Alzheimer’s disease. The MTL is highly vulnerable to amyloid plaque buildup in Alzheimer’s disease and contains structures important for memory, including the hippocampus and entorhinal cortex. Typically a scalp EEG is used for measuring seizure activity, but because the MTL is buried deep within the brain, it’s difficult to observe in this way. The researchers got around this problem by inserting electrodes directly into the patients’ MTL.

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This figure shows the placement of the electrodes in one of the patients.

Patient 1 showed high neuronal activity in the MTL, ranging from 400 spikes per hour when awake to 850 spikes per hour during sleep. The electrodes recorded three small seizures during the 12-hour monitoring period, all of which occurred during sleep. One caused the patient to awaken, while the others had no noticeable effect. When the patient was treated with levetiracetam, an antiepileptic drug, the spiking activity in the MTL was reduced by 65% and she experienced no further seizures for the next 48 hours before the electrodes were removed.

The second patient had comparatively lower neuronal activity: about 16 spikes per hour when awake and 190 spikes per hour during sleep. Mood disturbances prevented her from being administered the levetiracetam.

In both patients, 95% of the spikes and all of the seizures in their MTL were not detectable by EEG, which was recording at the same time as the electrodes. Thus these clinically silent seizures have remained unknown until now, invisible to both patients and doctors. This new electrode recording method shows that patients in the early stages of Alzheimer’s disease may have hyperactive neurons in the MTL, a possible explanation for why this region is often affected by high amyloid-beta levels. If this is the case, some patients may benefit from antiepileptic drugs to prevent Alzheimer’s disease from progressing further.

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While EEG (pictured here) is an easy and noninvasive method of measuring neuronal activity, this study showed that is cannot reliably detect seizures in subcortical structures like the hippocampus.

With only two patients, it’s hard to say whether this study generalizes to the rest of the population. These patients could be exceptions to the rule and display unusually high MTL activity. However, the study is certainly intriguing and merits further investigation with a larger number of test subjects.

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