Report from Neuroscience 2016

Posted by Sam Maddox in Research News on December 01, 2016 # Research

I was recently in San Diego for the annual Society for Neuroscience (SFN) meeting, a six-day show-and-tell data-fest that drew more than 30,000 scientists from all over the world presenting over 15,000 research projects. The subject matter is wide and deep, beyond the reach of any individual to absorb even a fraction of its entirety. You could spend the whole week just perusing the autism section, or the stroke, pain, immunology or addiction areas, and on it goes. I won’t list all the categories but see for yourself with the 2016 SFN meeting planner. The comparatively small niche that relates to spinal cord trauma is almost manageable, although the path overlaps subspecialties all over the floor.

First, a tribute. Ben Barres, Ph.D., a Stanford biologist whose lab is one of the seven in the Reeve International Research Consortium on Spinal Cord Injury, received SFN’s highest honor, the Ralph W. Gerard Prize in Neuroscience. Thomas Jessell, Ph.D., from Columbia University, was also recognized; each gets $25,000.

From an SFN press release:

Barres has made seminal contributions to our understanding of the mechanisms that control the formation of neural connections within the developing brain. He has elucidated fundamental molecular mechanisms by which glial cells control the formation and elimination of CNS synapses. His findings revealing that astrocytes and microglia normally prune synapses in the developing brain have also provided evidence that aberrant synapse pruning drives neurodegenerative processes in the adult brain with important implications for new treatments for Alzheimer’s and other neurological diseases.

Even while making such important discoveries, Barres devoted time to mentor others and advocate for women in science. As an openly transgender man, he has a unique perspective on gender issues in academia and has become a visible figure in the national dialogue about the barriers facing women in scientific careers.

Barres, alas, was diagnosed in 2015 with pancreatic cancer. He has kept his many friends and fans up-to-date on his health; happily, he reported in late October, his serum biomarker levels responded to chemotherapy treatment and were in a normal range. “To be clear,” he wrote, “I still have a pancreas tumor and innumerable liver mets [metastases] but they are smaller and presumably less metabolically active.” Barres says he deals with nausea and fatigue but is feeling pretty good. “Overall these days I reflect frequently about how very lucky I have been to have had a lab and such wonderful students and friends (all of you)!”

The Barres lab was represented at SFN by his post-doc Shane Liddelow, who, as first author, presented a poster (a 3 x 5 foot science fair-type summary) of a project that will be published soon in Nature, regarding neurotoxic reactive astrocytes. The gist of this work is that a reactive astrocyte called A1, activated by immune cells called microglia, is responsible for a lot of the deadly mayhem that leads to Alzheimer’s disease, Huntington disease, ALS or MS. The upside is that antibodies to A1 can neutralize it and perhaps head off these diseases.

When the full Nature paper comes out, we will of course share the results here. Meanwhile, be well, Dr. B., from one of your many fans.

So many posters, so much to absorb. Here are a few projects that caught my eye:

From the Phil Popovich lab at Ohio State, a poster called “BB5 - CX3CR1-deficient microglia and macrophages enhance endogenous repair, axon sprouting and synaptogenesis after spinal cord injury in mice.” This lab is interested in the immune system as it intersects with the nervous system, and also with the digestive system (we reported recently that this group treated SCI symptoms in animal experiments with a probiotic). The SFN poster is about reducing destructive immune responses from macrophage and microglia cells; using a chemical receptor to block a chemical trigger called CX3CR1, they were able to quiet the immune cells and thereby enhance nerve growth and recovery after SCI.

Here’s a poster from the Zhigang He lab at Harvard; He is a leading researcher in genetic modification, e.g. PTEN deletion, to switch on intrinsic axon growth. Here, the lab reported that a gene called ARMCX1 promotes mitochondrial transport, neuronal survival and axonal regeneration. This gene works on cells that PTEN deletion alone doesn’t affect. Says the poster: “ARMCX1 represents a potential new target for designing neural protective and repair strategies after injury.”

PTEN redux: More on the gene mod technique of PTEN deletion, from Os Steward at UC Irvine, presented by lead author Erin Gutilla, whose work we have reported before. “Adult deletion of PTEN in cortical motoneurons leads to robust cell body enlargement that is maintained as the steady-state cell size.” The title says it all – this result suggests that PTEN deletion might prevent neurons from the stress of aging, injury or disease.

From Murray Blackmore and his group at Marquette, a poster titled “Combined expression of pro-regenerative transcription factors and transplanted stem cells to promote corticospinal tract regeneration.” Blackmore previously reported that forced overexpression of certain transcription factors, including Sox11 and KLF7, promotes axon growth in the corticospinal tract (CST) of the spinal cord [important for major activities, such as walking]. In this study they set out to improve regeneration in a more complete spinal injury model – combining genetic manipulation of injured cortical neurons with transplantation of embryonic and induced pluripotent stem (iPS) cells into C5 injury sites. Did it work? The title would suggest it does but the detail says it’s too soon to tell (that’s the way it is with a lot of presentations at SFN – we get a taste of the work but it’s too early for a result).

In another poster, the Blackmore group presented another gene, KLF6, which acts as a potent transcriptional promoter of axon regeneration in the injured CST.

Two work-in-progress posters from the Chet Moritz lab at the University of Washington. (Moritz joined the Reeve Research Consortium last year.) The first, “Closed-loop neural interfacing strategies for the bladder,” led by Tom Richner and including James Fawcett (also a member of the Reeve Consortium) reports on progress toward a wireless bladder neuroprosthesis in an animal model. Part of the model uses light sensitive cell transplants (optogenetics) to activate bladder muscle as needed.

The other poster from the Moritz group carries forward the optogenetic idea toward long-term stimulation of the spinal cord. Sarah Mondello was on hand to present the work, which explained development of a high-powered LED implant to activate spinal cord cells, and therefore forelimb movements, for at least 6-8 weeks following implantation. This is useful for research, to understand complex circuits and movement parameters, but the lab suggests there may also be some therapeutic potential for this tool.

From Veronica Tom’s lab at Drexel: “Pharmacologically inhibiting soluble tumor necrosis factor α signaling mitigates autonomic dysreflexia (AD) and improves cardiovascular function after a complete high thoracic spinal cord injury.” AD is a dangerous consequence of high-level spinal cord injury, due to unruly growth of sensory nerves below the injury, indirectly leading to a spike in blood pressure. This dysfunction is related to a signal molecule called cytokine soluble tumor necrosis factor α (sTNFα). A biologic called XPro1595 inhibits sTNFα signaling, thus dramatically diminishes AD. Not clinical-grade yet, but moving that way.

From the lab of Chun-Li Zhang at UT Southwestern in Dallas. “Direct reprogrammed adult human motor neurons for disease modeling and drug identification.” Zhang’s work goes beyond cell transplants toward reprogramming cells in the body. In this study, this group used small molecules and transcription factors to directly reprogram adult skin cells (fibroblasts) into spinal motor neurons. This has great therapeutic patient-specific potential for motor neuron diseases, without immune rejection issues.

From the Miami Project, James Guest as Principal Investigator: “Assessment of the combined effects of chondroitinase and autologous Schwann cells on hand function after cervical SCI in primates.” This is a combo treatment that has to be tested in larger animals before it can move to human studies. From the poster:

Chondroitinase ABC (Chase) and Schwann cells have been shown independently to promote functional recovery in rodents after contusive injury. Autologous human Schwann cells ahSC are being tested in Phase 1 clinical trials for sub-acute and chronic SCI. Recognizing the necessity of combination strategies, we are exploring the acute injection of a lentiviral transfer vector carrying a mammalian compatible engineered chABC gene (LV-chABC), with or without sub-acute aSC transplantation, in primates following unilateral C3/4 SCI. Here, we present the preliminary evaluation of the hand and arm recovery up to six months post-injury and treatment.

Results: Significant differences in retrieval time and retrieval quality were found between the left (control) and right (injured) hand in each animal and between the 3 groups as of 6 months post-injury. LV-chABC injected animals showed the most rapid recovery. Additionally observed differences include the rate to reach hand function plateau and the variety of strategies developed to perform the task. Conclusions: Animals continue to survive. The tests discriminate recovery of fine dexterity of finger movements from adaptation strategies. Deficits and recovery of combined upper and lower extremity gait coupling are assessed with treadmill kinematics.

The National Paralysis Resource Center website is supported by the Administration for Community Living (ACL), U.S. Department of Health and Human Services (HHS) as part of a financial assistance award totaling $8,700,000 with 100 percent funding by ACL/HHS. The contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement, by ACL/HHS, or the U.S. Government.