Study Finds Link Between Spinal Cord Injuries and Metabolic Disruptions
A groundbreaking study conducted by researchers at Ohio State University has uncovered a significant link between spinal cord injuries (SCI) and metabolic dysfunctions, such as diabetes and heart disease. The study reveals that abnormal neuronal activities following an SCI lead to excessive breakdown of triglycerides in fat tissue, releasing harmful compounds into organs like the liver.
However, the research team has now identified a potential solution. In animal models, the administration of gabapentin, a nerve pain medication, proved effective in preventing these metabolic effects, paving the way for potential new treatments to mitigate the secondary health issues caused by spinal injuries.
Key Findings
- The study establishes a link between abnormal neuronal activity following a spinal cord injury and metabolic dysfunctions affecting fat tissue.
- By inhibiting problematic neural proteins and preventing the excessive breakdown of fats, gabapentin successfully normalizes metabolic functions in animal models.
- It is important to note that while gabapentin has considerable benefits, it can induce insulin resistance. Researchers are actively adjusting dosing strategies to both ensure therapeutic effects and minimize side effects.
Source: Ohio State University
A new animal study conducted at Ohio State University has revealed a strong correlation between abnormal post-injury neuronal activity and the development of pathological conditions such as diabetes, heart attack, and vascular diseases in individuals with spinal cord injuries. The study found that, following spinal cord injury, there is a leakage of abdominal fat tissue compounds, which pool in organs such as the liver. This, in turn, can result in the diagnosis of various conditions related to cardiometabolic diseases.
Researchers found that a short course of the nerve pain medication, gabapentin, successfully prevented the damaging metabolic effects of spinal cord injuries in animal models. The medication was found to inhibit a neural protein that, after the injury, becomes overactive and disrupts communication. By targeting this protein, gabapentin was able to normalize metabolic function in the animals.
According to senior author Andrea Tedeschi, Assistant Professor of Neuroscience at Ohio State University’s College of Medicine, the fat tissue undergoes changes due to maladaptive reorganization of the sensory system following a spinal cord injury. This reorganization initiates a harmful chain of reactions that cause triglycerides to break down and release harmful compounds, setting the stage for conditions such as insulin resistance. However, the administration of gabapentin restores metabolic function, creating the potential for improved treatment outcomes.
Cardiometabolic diseases, which include hypertension, dyslipidemia, and insulin resistance, are known to be more common among individuals with spinal cord injuries. While previous research has mainly focused on the sympathetic nervous system and its role in adipose tissue function, this study highlights the significance of sensory neurons in the development of metabolic dysfunctions following spinal cord injuries.
Debasish Roy, a postdoctoral researcher in the Tedeschi Lab and the first author of the paper, explored the connection between sensory neurons and adipose tissue. The research team found a cascade of abnormal activity within these neurons and visceral fat tissue after only one week of a spinal cord injury. As sensory neurons communicate with the fat tissue, changes in the fat and its interaction with CGRP, a neuropeptide, were observed. This lead to a chain of harmful effects, including lipolysis and an increase in blood flow in the fat tissue.
Alpha2delta1, a neuronal receptor protein, was found to be overexpressed after a spinal cord injury. Targeting this protein was pivotal in normalizing fat tissue function. The study demonstrated that gabapentin, a medication that targets alpha2delta1 and its partner, alpha2delta2, provided promising results in restoring metabolic function after spinal cord injuries.
While gabapentin exhibited insulin resistance as a side effect, the research team utilized a combination of high dosing and a measured dose reduction strategy to minimize side effects while maximizing therapeutic effects. By discontinuing the administration of the medication after four weeks, the team successfully normalized metabolism and lipid spillover in the liver, producing exciting results.
Finally, the team studied the effects of the genetic deletion of alpha2delta1 and the use of gabapentin on genes responsible for controlling adipose tissue. Both interventions resulted in the suppression of genes responsible for disrupting metabolic functions after spinal cord injuries. These findings provide insight into the benefits of early gabapentin treatment, which may help protect against harmful fat tissue conditions and decrease the risk of side effects.
Funding: This research received support from grants provided by the National Institute of Neurological Disorders and Stroke and the National Institutes of Health, as well as the Chronic Brain Injury program at Ohio State.
Authors: Researchers from Ohio State University
Original Research: The study is published in Cell Reports Medicine. (Read the study here)
