Jefferson Investigates: Mood Changes after TBI, Chlamydia’s Cellular Tricks, Modulation of Pain Signals

Mood & Cognition Changes after Traumatic Brain Injury

Mental health issues are common in people with traumatic brain injury (TBI) and can continue for years. They may be related to the brain injury itself or may result from patients’ challenges with everyday functions.

In a recent study, Jefferson Health researchers investigated levels of depression and apathy in older adults with TBI. Amanda Rabinowitz, MD, PhD, a brain injury researcher at Thomas Jefferson University, says the conditions are distinct in this way: Depression is a loss of pleasure and interest in things, whereas apathy is a state of low motivation or a failure to engage in life activities.

Both  conditions have been reported in older adults with dementia and with Parkinson’s disease, but there’s little data on apathy in people with TBI. Dr. Rabinowitz and her colleague, Umesh Venkatesan, PhD, both of whom work at the Jefferson Moss Rehabilitation Research Institute, sought to understand whether depression and/or apathy lead to changes in cognition or engaging in daily tasks, especially social engagement.

In their study, people with apathy were more likely to have cognitive problems — particularly with executive functions like working memory and attention control. People with depression were less likely to engage in societal activities. Those who showed signs of both apathy and depression had poorer overall functioning.

Awareness of these relationships has important clinical implications. For instance, some outcomes may signal a progression of brain injury in older adults, Dr. Rabinowitz says. Further, if apathy is a consequence of an injured brain, then it may also be “a harbinger of other neurological changes that need tracking, such as dementia and cognitive decline."

In addition, the conditions may require different therapeutic approaches. Treatment for depression is well-established — talk therapy and medication, for instance — although the particulars of depression in the context of TBI is less clear. Little clinical guidance exists for apathy.

“We need to know more,” Dr. Rabinowitz says. “How closely can we tailor our treatments to the individual?”

By Jill Adams

How Chlamydia Forms Protective Bubbles to Survive inside Human Cells

The bacterium chlamydia trachomatis is a major cause of sexually transmitted diseases. Bacteria have lots of tricks up their sleeve that help them survive inside cells. One strategy that chlamydia uses is to form protective “bubbles,” called inclusions, which fuse their membranes together to create large pockets of bacteria inside cells. Now, a new study by researchers at Thomas Jefferson University, published in Nature Communications, has shed light on the mechanisms behind this process.

Membrane fusion is important during infection because when some people are infected with non-fusing chlamydia, they tend to have much milder cases.

“It looks like fusion is boosting the potency of chlamydia,” says Fabienne Paumet, PhD, a biology researcher and senior author on the study.

Dr. Paumet’s team – led by first author Christine Linton, a PhD student in the lab – used microscopy tools to analyze genetically-modified chlamydia as they underwent membrane fusion. They found that the bacteria used a unique mechanism not seen before.

They observed that for membrane fusion to happen, two “bubbles” needed to form dedicated connection zones that acted like “docking and fusion stations.” These areas, called inclusion contact sites, were packed with special fats and proteins that prepared the membranes for fusion.

The mechanism differs from membrane fusion by eukaryotic organisms or viruses. In eukaryotic organisms, for example, Dr. Paumet compares membrane fusion to a zipper, where the cellular machinery on each side of the connecting membranes is different but complementary; in contrast, the proteins on chlamydial inclusion membranes were exactly the same on both sides.

Dr. Paumet says this research could one day have clinical applications. While antibiotic-resistant chlamydia is currently very rare, it’s likely to become more common in the future. If researchers know more about how chlamydia membrane fusion works, they could one day harness those mechanisms to fight infections that no longer respond to antibiotics.

“The more we know about chlamydia, the more it gives us tools to eventually interfere with it,” Dr. Paumet says.

By Marilyn Perkins

How the Nervous System Modulates Pain Signals

Sensory neurons that respond to temperature, touch and pain have ways of adapting to repeated stimuli that can change how a body experiences those sensations. In a recent paper, Thomas Jefferson University researchers describe a specific molecular change that accounts for this altered neuronal activity and, in turn, the strength of pain sensation.

Neurons send signals via action potentials, which involves a rapid exchange of ions across tiny conduits in the membrane called ion channels. Ion channels also work to quickly end this exchange. This electrical discharge is responsible for the remarkable speed and versatility of signaling in our nervous system.

With repeated firing, action potentials get progressively longer (they’re still fast, but not as fast). Neuroscientists have observed this phenomenon for years, but the mechanism was poorly understood. The new study clarifies: A molecular change in a specific potassium ion channel speeds up their closing and lengthens the action potential.

“This potassium channel is a major player in ending action potentials, but its function depends on a critical chemical modification,” says neuroscientist and senior author of the study, Manuel Covarrubias, MD, PhD. Namely, a group of chemicals called phosphate groups are added to the potassium channel to make it more efficient at terminating action potentials. When the channel doesn’t have enough of these chemicals, it doesn’t close as easily, and sensory stimulation that causes repeated firing makes action potentials longer and increases pain.

Through painstaking experimentation, Dr. Covarrubias and his research team, including MD/PhD student Tyler Alexander, has ascertained the specific phosphate tagging sites on the particular potassium channel that leads to longer action potentials. Now there’s a target for potential therapeutic intervention. In short, a treatment that boosts potassium channel function could alleviate clinically relevant pain conditions. This work is a stellar example of how basic research in molecular detail opens the door to potentially novel approaches in clinical translation.

By Jill Adams