Neuroscientists link memory fundamentals with Alzheimer’s disease in promising study

Paul Frankland

Paul Frankland

Deteriorating memory function is a scary, life changing symptom associated with Alzheimer’s disease (AD) – a neurodegenerative disease exhibited by cognitive declines such as speech, behaviour and thinking processes. Even though it is the most common form of dementia and the prevalence is continuously rising, there is no cure. While there are medications to help with symptoms, the disease ultimately results in mortality.

Drs. Paul Frankland and Sheena Josselyn, both Senior Scientists in the Neurosciences & Mental Health Program at the SickKids Research Institute, have been studying memory, in hopes of applying their findings to AD treatment.

“I think how we learn to remember things is the most fascinating subject. We are the sum total of our memories. Alzheimer’s disease really robs you of your identity,” says Josselyn.

The two were part of a team that took rejuvenating neurogenesis – a term for neuron generation – one step further.

The hippocampus is one of the few regions of the brain where neurogenesis continues after teenage development. AD patients do not have neurons produced in the hippocampus. Scientists have been studying neurogenesis and its benefit on retaining memories, believing that adding new neurons should improve memory function. After therapeutic benefits had been proven by stimulating different areas of the brain in Parkinson’s patients, interest in applying this to other neurological conditions grew.

The consequences of the disease is what inspires Joselyn’s passion for memory research. “A lot of the time, people who study Alzheimer’s look at cells in a dish. They forget that it’s really about memory -how you remember your past, how you could forget the name of your kids and not recognize people. So for us, that’s a hugely motivating factor.”

Naturally, the next step for Frankland and Josselyn was to determine if stimulating the hippocampus could benefit an animal that models AD by increasing neuron production, hopefully resulting in better memory function.

“There are very few FDA approved drugs for Alzheimer’s and they don’t work very well, so Paul started thinking outside the box. Let’s look at basic processes of how we know memories are made, and let’s apply this to a mouse model of Alzheimer’s,” says Josselyn.

Mice with gene mutations that mimic AD were used in their newest study. Just like patients, these mice seem to have memory problems in mazes, and also develop plaques in the brain, one of the trademark features of AD.

There were two groups; six weeks old mice (the human equivalent to a late teenager), and six months old mice (the human equivalent to a middle aged adult). The mice performed two tasks; a maze they were trained in, then had to find their way when placed in the maze later, and an associative memory task that involved testing to see if they recognized or were scared by freezing in a place they had been in once before.

“We used both young and old mice because we were interested to discover the effects of tackling Alzheimer’s early versus when it has progressed,” says Frankland. “The surprising result was that memory improved whether they were young or old. Plaque in the brain also decreased in young mice, so we improved both the behaviour and pathology.”

Now that Frankland, Josselyn and their team have proved that neurogenesis improves memory function, what’s next? Stimulating neurogenesis involves a very invasive brain surgery, and the results have been mixed. Finding a way to achieve the same effect with a pill could be promising to slow, or even reverse progression of the disease.

Frankland hopes World Alzheimer’s Day will be less relatable in the future. “Almost all of us are affected by Alzheimer’s, directly or indirectly. This gives us motivation to hope to reduce the prevalence of the disease, and improve the lives of existing patients.”

Frankland and Josselyn’s research was made possible by a donation from Jim Nicol and Christine Milne to SickKids Foundation.

Source of text: SickKids Hospital

Original Research Article:

Xia F, Yiu A, Stone SS, Oh S, Lozano AM, Josselyn SA, Frankland PW. Entorhinal Cortical Deep-Brain Stimulation Rescues Memory Deficits In Both Young And Old Mice Genetically Engineered To Model Alzheimer’s Disease. Neuropsychopharmacology. 2017 May 25. doi: 10.1038/npp.2017.100.

https://www.nature.com/articles/npp2017100