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Volume 11
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Article

Structural Degradation in Midcingulate Cortex Is Associated with Pathological Aggression in Mice

by
Sabrina van Heukelum
1,2,*,
Femke E. Geers
1,2,
Kerli Tulva
1,2,
Sanne van Dulm
1,2,
Christian F. Beckmann
1,2,
Jan K. Buitelaar
1,2,
Jeffrey C. Glennon
1,2,3,
Brent A. Vogt
4,5,
Martha N. Havenith
1,2,6,† and
Arthur S. C. França
1,2,†
1
Donders Institute for Brain, Cognition and Behavior, Radboudumc, 6525 EN Nijmegen, The Netherlands
2
Department of Cognitive Neuroscience, Radboudumc, 6525 EN Nijmegen, The Netherlands
3
Conway Institute of Biomolecular and Biomedical Research, School of Medicine, University College Dublin, Belfield, D04 Dublin, Ireland
4
Cingulum Neurosciences Institute, Manlius, NY 13104, USA
5
Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA 02118, USA
6
Zero-Noise Lab, Ernst Strüngmann Institute for Neuroscience, 60528 Frankfurt am Main, Germany
*
Author to whom correspondence should be addressed.
†
These authors contributed equally.
Brain Sci. 2021, 11(7), 868; https://doi.org/10.3390/brainsci11070868
Submission received: 28 May 2021 / Revised: 15 June 2021 / Accepted: 25 June 2021 / Published: 29 June 2021
(This article belongs to the Special Issue Dimensions of Pathological Aggression: From Neurobiology to Therapy)
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Abstract

Pathological aggression is a debilitating feature of many neuropsychiatric disorders, and cingulate cortex is one of the brain areas centrally implicated in its control. Here we explore the specific role of midcingulate cortex (MCC) in the development of pathological aggression. To this end, we investigated the structural and functional degeneration of MCC in the BALB/cJ strain, a mouse model for pathological aggression. Compared to control animals from the BALB/cByJ strain, BALB/cJ mice expressed consistently heightened levels of aggression, as assessed by the resident-intruder test. At the same time, immunohistochemistry demonstrated stark structural degradation in the MCC of aggressive BALB/cJ mice: Decreased neuron density and widespread neuron death were accompanied by increased microglia and astroglia concentrations and reactive astrogliosis. cFos staining indicated that this degradation had functional consequences: MCC activity did not differ between BALB/cJ and BALB/cByJ mice at baseline, but unlike BALB/cByJ mice, BALB/cJ mice failed to activate MCC during resident-intruder encounters. This suggests that structural and functional impairments of MCC, triggered by neuronal degeneration, may be one of the drivers of pathological aggression in mice, highlighting MCC as a potential key area for pathologies of aggression in humans.
Keywords: cingulate cortex; aggression; neuronal degeneration; astrogliosis; cFos; resident-intruder test cingulate cortex; aggression; neuronal degeneration; astrogliosis; cFos; resident-intruder test

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MDPI and ACS Style

Heukelum, S.v.; Geers, F.E.; Tulva, K.; van Dulm, S.; Beckmann, C.F.; Buitelaar, J.K.; Glennon, J.C.; Vogt, B.A.; Havenith, M.N.; França, A.S.C. Structural Degradation in Midcingulate Cortex Is Associated with Pathological Aggression in Mice. Brain Sci. 2021, 11, 868. https://doi.org/10.3390/brainsci11070868

AMA Style

Heukelum Sv, Geers FE, Tulva K, van Dulm S, Beckmann CF, Buitelaar JK, Glennon JC, Vogt BA, Havenith MN, França ASC. Structural Degradation in Midcingulate Cortex Is Associated with Pathological Aggression in Mice. Brain Sciences. 2021; 11(7):868. https://doi.org/10.3390/brainsci11070868

Chicago/Turabian Style

Heukelum, Sabrina van, Femke E. Geers, Kerli Tulva, Sanne van Dulm, Christian F. Beckmann, Jan K. Buitelaar, Jeffrey C. Glennon, Brent A. Vogt, Martha N. Havenith, and Arthur S. C. França. 2021. "Structural Degradation in Midcingulate Cortex Is Associated with Pathological Aggression in Mice" Brain Sciences 11, no. 7: 868. https://doi.org/10.3390/brainsci11070868

APA Style

Heukelum, S. v., Geers, F. E., Tulva, K., van Dulm, S., Beckmann, C. F., Buitelaar, J. K., Glennon, J. C., Vogt, B. A., Havenith, M. N., & França, A. S. C. (2021). Structural Degradation in Midcingulate Cortex Is Associated with Pathological Aggression in Mice. Brain Sciences, 11(7), 868. https://doi.org/10.3390/brainsci11070868

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