Biology subjects

Bakalian, M.

Publications and source records attributed to Bakalian, M..

3 recordsLinked to original sources

bioRxiv2024

A Human Brain Map of Mitochondrial Respiratory Capacity and Diversity

Mitochondrial oxidative phosphorylation (OxPhos) powers brain activity1,2, and mitochondrial defects are linked to neurodegenerative and neuropsychiatric disorders3,4, underscoring the need to define the brains molecular energetic landscape5-10. To bridge the cognitive neuroscience and cell biology scale gap, we developed a physical voxelization approach to partition a frozen human coronal hemisphere section into 703 voxels comparable to neuroimaging resolution (3x3x3 mm). In each cortical and subcortical brain voxel, we profiled mitochondrial phenotypes including OxPhos enzyme activities, mitochondrial DNA and volume density, and mitochondria-specific respiratory capacity. We show that the human brain contains a diversity of mitochondrial phenotypes driven by both topology and cell types. Compared to white matter, grey matter contains >50% more mitochondria. We show that the more abundant grey matter mitochondria also are biochemically optimized for energy transformation, particularly among recently evolved cortical brain regions. Scaling these data to the whole brain, we created a backward linear regression model integrating several neuroimaging modalities11, thereby generating a brain-wide map of mitochondrial distribution and specialization that predicts mitochondrial characteristics in an independent brain region of the same donor brain. This new approach and the resulting MitoBrainMap of mitochondrial phenotypes provide a foundation for exploring the molecular energetic landscape that enables normal brain functions, relating it to neuroimaging data, and defining the subcellular basis for regionalized brain processes relevant to neuropsychiatric and neurodegenerative disorders.

neuroscience↗

bioRxiv2019

Early Life Adversity, but not suicide, is associated with less prefrontal cortex gray matter in adulthood

BackgroundSuicide and major depression (MDD) are more prevalent in individuals reporting early life adversity (ELA). Prefrontal cortex volume is reduced by stress acutely and progressively in vivo, and changes in neuron and glia density are reported in depressed suicide decedents. We previously found reduced levels of the neurotrophic factor BDNF in suicide decedents and with ELA, and in the present study we sought to determine whether cortex thickness, neuron density or glia density in the dorsolateral prefrontal (BA9) and anterior cingulate (BA24) cortex are associated with ELA or suicide. MethodsA total of 52 brains, constituting 13 quadruplets of nonpsychiatric nonsuicide controls and MDD suicide decedents with and without ELA (n=13/group), all with psychological autopsy, were matched for age, sex and postmortem interval. Brains were collected at autopsy and frozen and blocks containing BA9 and BA24 were later dissected, post-fixed and sectioned. Sections were immunostained for NeuN to label neurons and counterstained with thionin to stain glial cell nuclei. Cortex thickness, neuron and glial density and neuron volume were measured by stereology. ResultsCortical thickness was 6% less with an ELA history in BA9 and 12% less in BA24 (p<0.05), but not in depressed suicide decedents in either BA9 or BA24. Neuron density was not different in ELA or in suicide decedents, but glial density was 17% greater with ELA history in BA9 and 15% greater in BA24, but not in suicides. Neuron volume was not different with ELA or suicide. DiscussionReported ELA, but not the stress associated with suicide, is associated with thinner prefrontal cortex and greater glia density in adulthood. ELA may alter normal neurodevelopment and contribute to suicide risk.

neuroscience↗

bioRxiv2017

Association of BDNF Val66Met Polymorphism and Brain BDNF levels with Major Depression and Suicide

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is implicated in the pathophysiology of major depressive disorder (MDD) and suicide. Both are partly caused by early life adversity (ELA) and ELA reduces both BDNF protein and gene expression. This study examines the association of BDNF Val66Met polymorphism and brain BDNF levels with depression and suicide. We hypothesized that both major depression and ELA would be associated with the Met allele and lower brain BDNF levels. Such an association would be consistent with low BDNF mediating the effect of ELA on adulthood suicide and MDD. METHODS: BDNF Val66Met polymorphism was genotyped in postmortem brains of 37 suicide decedents and 53 non-suicides. Additionally, BDNF protein levels were determined by Western blot in dorsolateral prefrontal cortex (Brodmann area 9; BA9), anterior cingulate cortex (ACC; BA24), caudal brainstem and rostral brainstem. The relationships between these measures and major depression, death by suicide and reported childhood adversity were examined. RESULTS: Depressed subjects had an excess of the Met allele and lower BDNF levels in ACC and caudal brainstem compared with non-depressed subjects. No effect of history of suicide death or early life adversity was observed with genotype, but lower BDNF levels in ACC were found in subjects who had been exposed to early life adversity and/or died by suicide compared to nonsuicide decedents and no reported childhood adversity. CONCLUSIONS: This study provides further evidence for low BDNF in major depression related to the BDNF met risk allele. Future studies should seek to determine how altered BDNF expression contributes to MDD and suicide.

neuroscience↗