Congratulations to the Neuroscience Graduate Program spring 2021 grads!

Everyone at the Division of Medical Sciences would like to extend our warmest congratulations to the Neuroscience Graduate Program (NGP) spring 2021 graduates!

Four trainees graduated from the program between April and June 2021: Dr. Eslam Mehina, Dr. Alicia Meconi, and Dr. Juan Triviño Paredes all successfully defended their PhD dissertations, and Keyrian Le Gratiet successfully defended his Master’s thesis. To celebrate, we’ve complied an overview of their work and their favourite memories as grad students, as well as a special video from some NGP faculty.

Dr. Eslam Mehina (PhD)

Supervisor: Dr. Craig Brown

Home department: Division of Medical Sciences

Thesis title: Investigating the Deleterious Effects of Type 1 Diabetes Mellitus on Microvascular Repair in the Mouse Cortex

Thesis summary: Using in vivo 2-photon microscopy and confocal imaging, Dr. Mehina showed how diabetes can affect the repair of microbleeds in the brain and how various macrophages respond to these injuries. (Such microbleeds, which are more common in individuals with diabetes, potentially contribute to the onset and progression of cognitive decline.) Dr. Mehina showed that 20 per cent of capillaries damaged by microbleeds were lost in individuals with diabetes, even with insulin or anti-inflammatory treatments. In contrast, microbleeds in healthy individuals repaired without exception. Dr. Mehina found a novel Mac2+/TMEM119- macrophage type associated with the microbleeds that failed to repair in individuals with diabetes, and that clodronate liposome treatments could improve repair rates by eliminating those cells. She also found that the brain’s innate immune cells are not necessary for capillary repair

Favourite NGP memory: Coffee walks with NGP friends and board games at the Grad House.

Dr. Alicia Meconi (PhD)

Supervisor: Dr. Brian Christie

Home department: Division of Medical Sciences

Thesis title: A Novel Preclinical Pediatric Concussion Model Causes Neurobehavioural Impairment and Diffuse Neurodegeneration

Thesis summary Developing new tools to help understand concussions and improve their diagnosis and treatment is a high priority. Historically, the clinical translation of preclinical basic research on concussions has been limited, as most models do not accurately mimic this form of mild traumatic brain injury (mTBI), and predominantly are only performed in male subjects. To address these limitations, we developed the awake closed head injury (ACHI) model that to study mTBI in male and female subjects. We also developed a clinically relevant neurological assessment protocol to better understand the neurobehavioral and pathological changes that accompany mTBI in both sexes. Our neurologic assessment protocol helps quantify changes in cognition, anxiety, and motor function; subtle cognitive impairments of executive function; as well as document any microscopic lesions, hemorrhages, and neurodegeneration. We found that when the head is accelerated rapidly by an “impulsive” force this results in the rapid onset of short-lived neurologic impairment. Normally these impairments resolve spontaneously, however in a minority of cases there were more prolonged deficits. Our results show these injuries are accompanied by subtle structural changes that can be discerned with in neuroimaging. The ACHI model is the first in Canada to show how mild brain injury, in the absence of anaesthesia, can induce mild neurocognitive impairment, and subtle structural deficits in the adolescent brains of male and female subjects.

Dr. Juan Triviño Paredes (PhD)

Supervisors: Dr. Patrick Nahirney and Dr. Brian Christie

Home department: Division of Medical Sciences

Thesis title: Repeated Mild Traumatic Brain Injury is Associated with Acute Microvascular Damage in Juvenile Male and Female Rats

Thesis summary: Mild traumatic brain injuries (mTBIs), also know as concussions, are the most common type of traumatic brain injury. Although lesions in the brains of mTBI patients are challenging to detect, even with modern imaging techniques, they can still cause cognitive and emotional alterations. Growing evidence suggests that while a single concussion may not cause significant damage, individuals who experience repeated mTBI (rmTBI), through sports or accidents, could experience significant microscopic damage to the brain. In this study, we found that rmTBI’s were associated with an increase in cerebral microbleeds (CMBs) in both juvenile males and females. The microbleeds occurred in a distributed fashion across several brain regions, rather than in the coup-contra-coup pattern that normally described for mTBI. These findings are important because CMBs have been identified as an early hallmark in brain trauma that can precede more severe neurodegenerative diseases. The cumulative effects of subtle but sustained microvascular damage could also explain the persistent long-term deficits observed in mTBI. This study provides evidence for the potential involvement of CMBs in the development of neurological deficits after rmTBI.

Favourite NGP memory: For me, it is always about the people. I will never forget meeting such an amazing group of people during my time in the NGP, including my supervisors, the other PIs, and especially all the students in the program. Getting to know all the very friendly and fun students in the NGP and sharing life experiences with them through these years made this journey very special.

Keyrian Le Gratiet (MSc)

Supervisor: Dr. Raad Nashmi

Home department: Biology

Thesis title: Differential Distribution of Functional Co-transmitted Cholinergic and GABAergic Synaptic Inputs onto Substantia Nigra Dopaminergic Neurons

Thesis summary: Communication within the brain relies on the release of neurotransmitters that bind to ligand-gated ion channels and modulate neuronal excitability. Our lab studies a specific class of ligand-gated ion channels, nicotinic acetylcholine receptors (nAChRs), which are activated by the neurotransmitter acetylcholine (ACh) and involved in motor control, sensory modulation, and higher executive functions. For my research, I focused on ACh-mediated neurotransmission onto dopaminergic (DA) neurons in the substantia nigra (SN), a brain region important for reward-coding of motor behaviours and found to be critically impaired in Parkinson’s disease. We have discovered a population of DA neurons in the medial substantia nigra that receives co-transmitted ACh and gamma aminobutyric acid (GABA), another neurotransmitter. My research examined in detail how cholinergic and GABAergic neurotransmission can modulate the excitability of DA neurons in this part of the brain by determining the spatial subcellular distribution of ACh and GABA inputs onto the soma and dendrites of those neurons and their synaptic properties. The localization and timing of converging synaptic inputs onto the dendritic tree defines the excitability of neurons and this research aimed to understand how cholinergic and GABAergic inputs can differentially shape dopaminergic output from the substantia nigra.

Favourite NGP memory: During our Neuroscience Graduate course, we were very fortunate to have access to brain tissue as part of our anatomy labs. This was a tremendously exciting and very humbling experience that helped strengthen our understanding of human neuroanatomy.

A Special Video Message from the NGP to the Spring 2021 Grads