Obesity can impair learning, memory

Obesity can break down our protective blood brain barrier resulting in problems with learning and memory, a study has found.

Chronic activation of the receptor, Adora2a on the endothelial cells that line this important barrier in our brain can let factors from the blood enter the brain and affect the function of our neurons, scientists said. The team has shown that when they block Adora2a in a model of diet-induced obesity, this important barrier function is maintained.

We know that obesity and insulin resistance break down the blood brain barrier in humans and animal models, but exactly how has remained a mystery, said a neuroscientist. In the brain, adenosine is a neurotransmitter that helps us sleep and helps regulate our blood pressure, in the body it's also a component of the cell fuel adenosine triphosphate, or ATP. Adenosine also activates receptors Adora1a and Adora2a on endothelial cells, which normally supports healthy relationships between brain activity and blood flow.

Problems arise with chronic activation, particularly in the brain, which is what happens with obesity, the author said. People who have obesity and diabetes have higher rates of cognitive impairment as they age and most of the related structural changes are in the hippocampus, a centre of learning and memory. Fat is a source of inflammation and there is evidence that reducing chronic inflammation in the brain helps prevent obesity-related memory loss.

For the study, young mice fed a high-fat diet got fat within 2 weeks, and by 16 weeks they had increases in fasting glucose and insulin concentrations, all signs that diabetes is in their future. In the minute vasculature of the hippocampus, the researchers saw the obesity first increased permeability of the blood brain barrier to tiny molecules like flurophore sodium fluorescein or NaFl. Diet-induced insulin resistance heightened that permeability so that a larger molecule, Evans Blue, which has a high affinity for serum albumin, the most abundant protein in blood, also could get through.

When they looked with electron microscopy, they saw a changed landscape. Resulting diabetes promoted shrinkage of the usually tight junctions between endothelial cells and actual holes in those cells. When they gave a drug to temporarily block Adora2a, it also blocked problems with barrier permeability. Whether that could work in humans and long term as a way to avoid cognitive decline in obese humans, remains to be seen, he said.

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Obesity can break down our protective blood brain barrier resulting in problems with learning and memory, a study has found. Chronic activation of the receptor Adora2a on the endothelial cells that line this important barrier in our brain can let factors from the blood enter the brain and affect the function of our neurons, scientists said. The team from Augusta University in the US have shown that when they block Adora2a in a model of diet-induced obesity, this important barrier function is maintained.

https://www.thehansindia.com/life-style/health/obesity-can-impair-learning-memory-study-523166

Obesity can break down our protective blood brain barrier resulting in problems with learning and memory, a study has found. Chronic activation of the receptor Adora2a on the endothelial cells that line this important barrier in our brain can let factors from the blood enter the brain and affect the function of our neurons, scientists said. The team from Augusta University in the US have shown that when they block Adora2a in a model of diet-induced obesity, this important barrier function is maintained.

https://www.thehansindia.com/life-style/health/obesity-can-impair-learning-memory-study-523166

IISc produces a salt to combat bacterial infections

It works better than the physical mixture of two drugs.

Using crystal engineering, a team of researchers from the Indian Institute of Science (IISc) Bangalore has successfully produced a highly efficacious binary salt of two commonly used drugs — norfloxacin (antibacterial) and sulfathiazole (antimicrobial).

The salt is more effective than a physical mixture of the two drugs. The results were published in the journal Molecular Pharmaceutics.
Better solubility

The two drugs were ground for nearly 30 minutes and made into a solution from which the salt was produced. It has enhanced pharmaceutical effects compared to the physical mixture of the two drugs.

The underlying reason for the salt’s improved efficacy is the better solubility and diffusion of the drugs, particularly norfloxacin and, therefore, enhanced bioavailability and pharmaceutical activity.

“Norfloxacin in a pure form or in a physical mixture has low solubility and permeability, so the amount of the drug that goes through the membrane and gets into tissues is less. To compensate for this, higher dosages of norfloxacin drug are generally used,” says Prof. Gautam R. Desiraju from the Solid State and Structural Chemistry Unit at IISc and the corresponding author of the paper.

But in the case of the binary salt, a “large enhancement in overall solubility” was seen at pH 7.4, which is generally seen in the small intestine where most of the absorption takes place. Most importantly, both the drugs showed comparable solubility when present in the salt form.

Similarly, in the case of permeability, the amount of binary salt diffusing through the membrane was much higher in the first hour. In contrast, the parent drugs show much lower diffusion. When the drugs are present together in a physical mixture, each one has a different rate of diffusion across the membrane.

Combating microbes

“But in the case of the binary salt both diffuse together. It is like sulfathiazole pulls norfloxacin across the membrane so both the drugs are available at the same time at the site of action to combat the microbes together,” he says.

“We are trying to study the mechanism behind the increased diffusion so that we have molecular level understanding of what precisely is happening,” Prof. Desiraju says.

“Generally the salt form increases solubility and because of high solubility or concentration gradient diffusion gets enhanced,” says Dr. Shanmukha Prasad Gopi from IISc and the first author of the paper.

Potency tested

The potency of the salt and the physical mixture of the drugs was tested on E. coli, Staphylococcus aureus and fungi. Studies showed that the salt was able to achieve the same result of inhibiting bacterial and fungal growth at about half the concentration of the physical mixture.

For the same dosage, the salt had nearly five times greater area that was clear of microbes than the physical mixture of the two drugs. “The salt has properties that are more than the aggregate of the individual properties,” Prof. Desiraju says.
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