Reversible behavioral deficits in rats during a cycle of demyelination-remyelination of the fimbria.

Abstract

Traumatic brain injury (TBI) selectively damages white matter. White matter damage does not produce deficits in many behavioral tests used to analyze experimental TBI. Rats were impaired on an active place avoidance task following inactivation of one hippocampal injection of tetrodotoxin. The need for both hippocampi suggests that acquisition of the active place avoidance task may require interhippocampal communication. The controlled cortical impact model of TBI demyelinates midline white matter and impairs rats on the active place avoidance task. One white matter region that is demyelinated is the fimbria that contains hippocampal commissural fibers. We therefore tested whether demyelination of the fimbria produces deficits in active place avoidance. Lysophosphatidylcholine (LPC) was injected stereotaxically to produce a cycle of demyelination-remyelination of the fimbria. At 4 days, myelin loss was observed in the fimbria of LPC-, but not saline-injected rats. Fourteen days after injection, myelin content increased in LPC-, but not saline-injected rats. Three days after injection, both saline- and LPC-injected rats had similar performance on an open field and passive place avoidance task in which the rat avoided a stationary shock zone on a stationary arena. The following day, on the active place avoidance task, LPC-injected rats had a significantly higher number of shock zone entrances suggesting learning was impaired. At 14 days after injection, saline- and LPC-injected rats had similar performance on open field and passive place avoidance. On active place avoidance, however, saline- and LPC-injected rats had a similar number of total entrances suggesting that the impairment seen at 4 days was no longer present at 14 days. These data suggest that active place avoidance is highly sensitive to white matter injury.

• Authors: Natalia M Grin'kina, Samah G Abdel-Baki, Peter J Bergold
• Journal: PloS one (PLoS One) Vol. 8 Issue 1 Pg. e53775 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23349742 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Lysophosphatidylcholines

Topics

• Animals
• Avoidance Learning (drug effects, physiology)
• Behavior, Animal (drug effects, physiology)
• Demyelinating Diseases (chemically induced, physiopathology)
• Fornix, Brain (drug effects, physiology, physiopathology)
• Lysophosphatidylcholines (pharmacology)
• Myelin Sheath (drug effects, physiology)
• Rats
• Rats, Sprague-Dawley
• Time Factors