Changes in Blood-Brain Barrier Function Associated with Conditioned Fear in Rats

Hayes, Ronald L.; Pechura, C. M.; Povlishock, J. T.; Becker, Donald P.

doi:10.1007/978-3-642-70696-7_32

Cited by 3 publications

(1 citation statement)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…EPI is a polar molecule that does not cross the blood-brain barrier (Weil-Malherbe et al, 1959 ) and Pnmt has almost no expression and enzymatic activity in the brain (Ho et al, 1974 ; Lew et al, 1977 ). However, there are some evidences that intense stressful situations can lead to physiological changes in blood-brain barrier permeability (Skultétyová et al, 1998 ; Sántha et al, 2016 ) and consequently in molecules that normally do not cross the blood-brain barrier (as is the case of EPI) might cross (Hayes et al, 1985 ). For that reason, we performed an experiment to understand if EPI could cross the blood-brain barrier to the brain tissue after our stress conditions using an EPI deficient (Pnmt-KO) mice.…”

Section: Discussionmentioning

confidence: 99%

Epinephrine Released During Traumatic Events May Strengthen Contextual Fear Memory Through Increased Hippocampus mRNA Expression of Nr4a Transcription Factors

Oliveira

Martinho

Serrão

et al. 2018

Front. Mol. Neurosci.

View full text Add to dashboard Cite

Epinephrine (EPI) strengthens contextual fear memories by acting on peripheral β2-adrenoceptors. Phenylethanolamine-N-methyltransferase-knockout (Pnmt-KO) mice are EPI-deficient mice and have reduced contextual fear learning. Our aim was to evaluate the molecular mechanisms by which peripheral EPI strengthens contextual fear memory and if a β2-adrenoceptor antagonist can erase contextual fear memories. Pnmt-KO and wild-type (WT) mice were submitted to fear conditioning (FC) procedure after treatment with EPI, norepinephrine (NE), EPI plus ICI 118,551 (selective β2-adrenoceptor antagonist), ICI 118,551 or vehicle (NaCl 0.9%). Catecholamines were separated and quantified by high performance liquid chromatography-electrochemical detection (HPLC-ED). Blood glucose was measured by coulometry. Real-time polymerase chain reaction (qPCR) was used to evaluate mRNA expression of nuclear receptor 4a1 (Nr4a1), Nr4a2 and Nr4a3 in hippocampus samples. In WT mice, plasma EPI concentration was significantly higher after fear acquisition (FA) compared with mice without the test. NE did not increase in plasma after FA and did not strengthen contextual fear memory, contrary to EPI. Freezing induced by EPI was blocked by ICI 118,551 in Pnmt-KO mice. In WT mice, ICI 118,551 blocked blood glucose release into the bloodstream after FA and decreased contextual fear memory. Nr4a1, Nr4a2 and Nr4a3 mRNA expression decreased in Pnmt-KO mice compared with WT mice after FC procedure. In Pnmt-KO mice, EPI induced an increase in mRNA expression of Nr4a2 compared to vehicle. In conclusion, EPI increases in plasma after an aversive experience, possibly improving long-term and old memories, by acting on peripheral β2-adrenoceptors. Glucose could be the mediator of peripheral EPI in the central nervous system, inducing the expression of Nr4a transcription factor genes involved in consolidation of contextual fear memories.

show abstract