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Breakthrough Discovery in Neurotransmission

Summary: Researchers discover the FABP5 protein is key to how endocannibinoids travel from neurons to receptors.

Source: University at Buffalo.

Samir Haj-Dahmane, PhD, senior research scientist at the University at Buffalo Research Institute on Addictions, has discovered how certain neurotransmitters are transported and reach their targets in the brain, which could lead to new drug therapies to help anxiety and other negative brain functions.

In a study published this week by the Proceedings of the National Academy of Sciences, researchers from RIA and Stony Brook University show that a particular protein, known as fatty-acid-binding protein 5 (FABP5), is key to how endocannabinoids travel from neurons to receptors in the brain. This research, led by Haj-Dahmane, was supported by the National Institutes of Health and SUNY REACH (Research Excellence in Academic Health).

Endocannabinoids are naturally produced lipids in the brain that control numerous physiological and behaviors functions, including emotions, stress, pain, motor control and cognition. Released from brain cells, endocannabinoids must travel through a liquid environment to reach and activate cannabinoid receptors and produce their physiological effects.

“For nearly 40 years, a long-standing question in the field of endocannabinoid research is how these lipids can travel through an aqueous (water-like) environment and reach their specific targets,” Haj-Dahmane says. “Our research identifies FABP5 as the critical element in achieving this process.”

This new discovery is a breakthrough in the current understanding of endocannabinoid function in the brain, which is significant because of the multiple physiological and behaviors function of the endocannabinoid system, including stress, addiction, memory, appetite and pain regulation.

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They then tested whether there were noticeable differences between men and women – and found that there were, with women’s smiles being more expansive.NeuroscienceNews.com image is credited to the researchers.

“Given the growing interest in the therapeutic potential of endocannabinoids, it is very likely that FABP5 will be the focus of future translational research to develop drug therapies for psychiatric and neurological disorders involving this system,” Haj-Dahmane says.

About this neuroscience research article

The study was co-authored by Roh-Yu Shen, PhD, and Panayotis (Peter) K. Thanos, PhD, of the UB Research Institute on Addictions, and Matthew W. Elmes, PhD, Keith Studholme, PhD, Marta P. Kanjiya, PhD, Diane Bogdan, PhD, Jeremy T. Miyauchi, PhD, Stella E. Tsirka, PhD, Dale G. Deutsch, PhD, and Martin Kaczocha, PhD, of Stony Brook University.

Funding: RIA is a research center of the University at Buffalo and a national leader in the study of alcohol and substance abuse issues. RIA’s research programs, most of which have multiple-year funding, are supported by federal, state and private foundation grants. Located on UB’s Downtown Campus, RIA is a member of the Buffalo Niagara Medical Campus and a key contributor to UB’s reputation for research excellence.

Source: Cathy Wilde – University at Buffalo
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is credited to the researchers.
Original Research: Abstract in PNAS.
doi:10.1073/pnas.1721339115

Cite This NeuroscienceNews.com Article
University at Buffalo “Breakthrough Discovery in Neurotransmission.” NeuroscienceNews. NeuroscienceNews, 15 March 2018.
<http://neurosciencenews.com/neurotransmission-breakthrough-8642/>.
University at Buffalo (2018, March 15). Breakthrough Discovery in Neurotransmission. NeuroscienceNews. Retrieved March 15, 2018 from http://neurosciencenews.com/neurotransmission-breakthrough-8642/
University at Buffalo “Breakthrough Discovery in Neurotransmission.” http://neurosciencenews.com/neurotransmission-breakthrough-8642/ (accessed March 15, 2018).

Abstract

Fatty-acid–binding protein 5 controls retrograde endocannabinoid signaling at central glutamate synapses

Endocannabinoids (eCBs) are lipid-signaling molecules involved in the regulation of numerous behaviors and physiological functions. Released by postsynaptic neurons, eCBs mediate retrograde modulation of synaptic transmission and plasticity by activating presynaptic cannabinoid receptors. While the cellular mechanisms by which eCBs control synaptic function have been well characterized, the mechanisms controlling their retrograde synaptic transport remain unknown. Here, we demonstrate that fatty-acid–binding protein 5 (FABP5), a canonical intracellular carrier of eCBs, is indispensable for retrograde eCB transport in the dorsal raphe nucleus (DRn). Thus, pharmacological inhibition or genetic deletion of FABP5 abolishes both phasic and tonic eCB-mediated control of excitatory synaptic transmission in the DRn. The blockade of retrograde eCB signaling induced by FABP5 inhibition is not mediated by impaired cannabinoid receptor function or reduced eCB synthesis. These findings indicate that FABP5 is essential for retrograde eCB signaling and may serve as a synaptic carrier of eCBs at central synapses.

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