TY - JOUR
T1 - MEMRI reveals altered activity in brain regions associated with anxiety, locomotion, and cardiovascular reactivity on the elevated plus maze in the WKY vs SHR rats
AU - Zubcevic, Jasenka
AU - Watkins, Jacqueline
AU - Perez, Pablo D.
AU - Colon-Perez, Luis M.
AU - Long, Maureen T.
AU - Febo, Marcelo
AU - Hayward, Linda
N1 - Funding Information:
Funding This research was supported by the American Heart Association grant 14SDG18300010 and University of Florida College of Veterinary Medicine (UFCVM) Start Up Funds to JZ and the UFCVM Fall Faculty Competition to ML and LFH.
Funding Information:
Acknowledgements The authors thank the Advanced Magnetic Resonance Imaging and Spectroscopy (AMRIS) facility for their continued support (National Science Foundation Cooperative Agreement No. DMR-1157490 and the State of Florida). The authors thank Drs. Craig F. Ferris and Praveen Kulkarni (Northeastern University, Boston) for kindly providing the rat brain atlas used in the present work.
Funding Information:
The authors thank the Advanced Magnetic Resonance Imaging and Spectroscopy (AMRIS) facility for their continued support (National Science Foundation Cooperative Agreement No. DMR-1157490 and the State of Florida). The authors thank Drs. Craig F. Ferris and Praveen Kulkarni (Northeastern University, Boston) for kindly providing the rat brain atlas used in the present work. • Increased behavioral anxiety in WKY rats is linked to heightened autonomic activity. • High trait anxiety in the WKY is associated in increased resting activity in the amygdala. • MEMRI identifies elevated neuronal activity in the pons of the SHR linked to hypertension/increased mobility. Author J Zubcevic declares that she has no conflict of interest. Author J Watkins declares that she has no conflict of interest. Author P Perez declares that he has no conflict of interest. Author L Colon-Perez declares that he has no conflict of interest. Author M Long declares that she has no conflict of interest. Author M Febo declares that he has no conflict of interest. Author L Hayward declares that she has no conflict of interest.
Publisher Copyright:
© 2017, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2018/10/1
Y1 - 2018/10/1
N2 - Individuals with anxiety/depression often have exaggerated cardiovascular responses to stressful stimuli and a comorbidity with hypertension. Alternatively, individuals with hypertension can be more anxious. In the present study cardiovascular changes were evaluated during behavioral testing of anxious behavior on the elevated plus maze (EPM) in the spontaneously hypertensive rat (SHR), a rodent model of neurogenic hypertension, and compared to the response of the more anxious, but normotensive, Wistar-Kyoto rat (WKY). Manganese-enhanced magnetic resonance imaging (MEMRI) was used to identify regional differences in baseline brain activity. Parallel to indicators of elevated behavioral anxiety on the EPM, WKYs had a greater increase in blood pressure but not heart rate when compared to the SHR while on the EPM. Associated with differences in anxiety-related behavior and autonomic responses, we observed increased baseline activity in the amygdala, central gray, habenula and interpeduncular nucleus with MEMRI of the WKY compared to the SHR. Conversely, elevated baseline brain activity was found in regions associated with blood pressure control and system arousal, including the hypothalamus, locus coeruleus and pedunculopontine tegmental nucleus, in the SHR vs WKY, in-line with increased resting blood pressure and increased mobility in this strain. Lastly, reduced activity in hippocampal regions was identified in the SHR compared to the WKY and may be associated with cognitive impairment previously reported in the SHR. Thus, autonomic reactivity may be a true measure of stress in rodent models of anxiety and MEMRI presents a powerful technique to uncover novel brain mechanisms of blood pressure control.
AB - Individuals with anxiety/depression often have exaggerated cardiovascular responses to stressful stimuli and a comorbidity with hypertension. Alternatively, individuals with hypertension can be more anxious. In the present study cardiovascular changes were evaluated during behavioral testing of anxious behavior on the elevated plus maze (EPM) in the spontaneously hypertensive rat (SHR), a rodent model of neurogenic hypertension, and compared to the response of the more anxious, but normotensive, Wistar-Kyoto rat (WKY). Manganese-enhanced magnetic resonance imaging (MEMRI) was used to identify regional differences in baseline brain activity. Parallel to indicators of elevated behavioral anxiety on the EPM, WKYs had a greater increase in blood pressure but not heart rate when compared to the SHR while on the EPM. Associated with differences in anxiety-related behavior and autonomic responses, we observed increased baseline activity in the amygdala, central gray, habenula and interpeduncular nucleus with MEMRI of the WKY compared to the SHR. Conversely, elevated baseline brain activity was found in regions associated with blood pressure control and system arousal, including the hypothalamus, locus coeruleus and pedunculopontine tegmental nucleus, in the SHR vs WKY, in-line with increased resting blood pressure and increased mobility in this strain. Lastly, reduced activity in hippocampal regions was identified in the SHR compared to the WKY and may be associated with cognitive impairment previously reported in the SHR. Thus, autonomic reactivity may be a true measure of stress in rodent models of anxiety and MEMRI presents a powerful technique to uncover novel brain mechanisms of blood pressure control.
KW - Anxiety
KW - Blood pressure
KW - Elevated plus maze
KW - Heart rate
KW - MEMRI
KW - SHR
KW - WKY
UR - http://www.scopus.com/inward/record.url?scp=85035123845&partnerID=8YFLogxK
U2 - 10.1007/s11682-017-9798-4
DO - 10.1007/s11682-017-9798-4
M3 - Article
C2 - 29181695
AN - SCOPUS:85035123845
SN - 1931-7557
VL - 12
SP - 1318
EP - 1331
JO - Brain Imaging and Behavior
JF - Brain Imaging and Behavior
IS - 5
ER -