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Faculty of Graduate Studies

Jylan Hofmeyer

  • B.Sc. Hons. (University of Applied Sciences Utrecht, 2024)
Notice of the Final Oral Examination for the Degree of Master of Science

Topic

Cannabinoid Type 1 Receptor Expression Across Limbic Circuits Following Repeated Mild Traumatic Brain Injury: Temporal, Regional, and Sex-Dependent Alterations in Adolescent Rats

School of Medical Sciences

Date & location

  • Friday, August 21, 2026
  • 12:00 P.M.
  • Medical Sciences Building, Room 150

Examining Committee

Supervisory Committee

  • Dr. Brian Christie, School of Medical Sciences, University of Victoria (Supervisor)
  • Dr. Patrick Nahirney, School of Medical Sciences, UVic (Member)
  • Dr. Raad Nashmi, School of Medical Sciences, UVic (Member)

External Examiner

  • Dr. Patricia de Souza Brocardo, Department of Morphological Sciences, Universidade Federal de Santa Catarina

Chair of Oral Examination

  • Dr. Daniela Constantinescu, Department of Mechanical Engineering, UVic

Abstract

Repeated mild traumatic brain injury (r-mTBI) is associated with persistent cognitive and emotional dysfunction, with accumulating evidence suggesting sex-dependent differences in susceptibility and recovery. The endocannabinoid system, via cannabinoid type 1 Receptors (CB1R), critically regulates synaptic excitation-inhibition balance within limbic circuits that support learning, memory, and emotional processing, including the hippocampus and amygdala. This thesis investigated whether r-mTBI alters CB1R expression across these regions during adolescence in a sex- and time-dependent manner. Adolescent male and female rats received three lateral mTBI impacts separated by 72 hours or sham procedures; neurological and behavioural outcomes were assessed, and CB1R expression was quantified at post-injury days (PID) 1, 7, and 30 using DAB immunohistochemistry and region- and layer-specific optical density analysis. CB1R expression exhibited dynamic temporal regulation, with the greatest injury-related divergence occurring at PID 7. Effects were region-, layer-, and sex-dependent. In hippocampal regions, male r-mTBI animals showed reduced CB1R expression relative to sham controls at PID 7, whereas females showed increased CB1R expression in CA1, dentate gyrus (DG), and hilus. The amygdala also showed a sex- and time-dependent response, with increased CB1R expression in female r-mTBI animals at PID 7. Layer-specific analyses suggested that male PID 7 reductions were most apparent in dendritic and input-associated hippocampal compartments, including CA1 stratum oriens, CA1 stratum radiatum, and the DG molecular layer. These injury-related differences were not significant at PID 1 and were attenuated by PID 30. Together, these findings suggest that adolescent r-mTBI produces transient, sex-specific alterations in CB1R expression within hippocampal and amygdalar circuits. The strongest injury-related differences emerged at PID 7, indicating that CB1R regulation may be particularly sensitive during the subacute post-injury period. These results support further investigation of endocannabinoid signalling as a mechanism contributing to sex-dependent limbic circuit responses after r-mTBI.

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