Initially, we also focused on the association of bipolar disorder with mtDNA . output to anterior cingulate cortex, nucleus accumbens and amygdala (Hsu et al., . More specifically, there are differences in the function and the structure of the mitochondria of neurons in the nucleus accumbens depending on. The nucleus accumbens (NAcc) is a prime region of interest, where inputs . Mitochondria were counted and normalized to an area of µm2. There was no difference in the area of the entire striatum between groups.
We used stereological analysis of electron micrographs in postmortem SZ to analyze the organization and composition of synapse types in the NAcc.
Methods Brain Tissue Postmortem human tissue was obtained from the Alabama and Maryland Brain Collections, with consent from the next of kin.
Mitochondrial function in the brain links anxiety with social subordination
The tissue was collected from 8 control and 6 SZ subjects. Cases were diagnosed based on patient medical records, family interviews, autopsy reports, and neuropathologic assessments. Control cases had no history of psychiatric or neurological disease. Pairs of control and SZ cases were chosen based on the best match of age, race, sex, postmortem interval PMIand tissue pH level.
This series was then used to create a mask of the NAcc core and shell boundary for use when blocking tissue for electron microscopy figure 1A. View large Download slide Ultrastructure of the human NAcc. Blocks from each region were then taken from an adjacent embedded section for EM.
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B A spine SP receives convergent input from axon terminals AT making asymmetric black arrowhead and symmetric white arrowhead synapses. The SP was observed through multiple serial sections and synaptic contact was made at each of the arrowheads. The neck of the SP is marked by the white arrows.
The primary antibody was mouse monoclonal anti-calbindin Sigma, C; 1: The secondary antibody was biotinylated horse anti-mouse IgG Vector Laboratories; 1: The immunohistochemistry protocol was performed as detailed previously. These sections nm thickness were collected using an ultramicrotome, mounted on glass slides, stained with Toluidine Blue and coverslipped for reference.
Serial ultrathin sections 90nm thickness from each block were mounted on Formvar-coated copper grids, and photographed at 80kV on a Hitachi transmission electron microscope, as detailed previously.
All synapses in this study were identified by the first and last authors. Micrographs were cropped and adjusted for brightness and contrast for presentation in the figures. Criteria for distinguishing a synapse were the presence of 1 parallel pre- and postsynaptic membranes, 2 a postsynaptic density PSDand 3 synaptic vesicles at the membrane in the presynaptic terminal.
Synaptic features quantified using stereology included the symmetry of the PSD and the postsynaptic target.
Neuropil only was quantified, cell bodies were not photographed. This yielded a total of synapses in Additionally, serial images were used to quantify PSD and mitochondrial measurements. Our findings highlight a key role for brain energy metabolism in social behavior and point to mitochondrial function in the nucleus accumbens as a potential marker and avenue of treatment for anxiety-related social disorders.
How Mitochondria Keep Our Brains and Minds Moving
In most socially living species, the social rank of an individual is established during competitive encounters with conspecifics. The outcome of these encounters determines the allocation of territory, resources and access to reproduction 1and greatly influences physiology and health 2.
Winning a social competition is rewarding, enhances rank in social hierarchies, and increases the probability of winning future contests 34. In humans, a low social status predicts morbidity and survival 5 and has also been linked to the development of psychopathologies 6. Despite the important consequences of social rank on health, little is known regarding the mechanisms underlying the establishment of social hierarchies.
One of the main reasons for the paucity of neurobiological mechanisms determining social hierarchies may be that social competition involves interacting subjects that both need to be taken into account. The competitors may exhibit different features such as size, age, gender, as well as previous social experience, all known to influence social competitiveness.
However, when subjects are matched for these characteristics, the impact of innate personality traits on social competitiveness may be investigated. One such personality trait, anxiety, may have important consequences for the outcome of social competitions. In humans, high-anxious individuals often display a subordinate status and report feelings of being overlooked and rejected 7and their competitive self-confidence becomes undermined under stress 8.
Thus, interindividual differences in anxiety could predetermine the outcome of a competitive encounter and, as such, trait anxiety may have important consequences for social status. However, the neural mechanisms whereby anxiety might affect social hierarchy formation are largely unknown. We addressed this question by examining social competitiveness between male rats characterized for trait anxiety.
Recent work has highlighted the potential for individual differences in mitochondrial function and, more broadly, energy metabolism to influence vulnerability to develop psychopathological disorders, such as anxiety and depression 9 — Here, we demonstrate that trait anxiety is a determining factor of social rank that is mediated by brain region-specific mitochondrial function.
How Mitochondria Keep Our Brains and Minds Moving – Association for Psychological Science
We show that manipulation of mitochondrial function in the nucleus accumbens NAc is sufficient to influence social rank, highlighting a key role for brain mitochondrial function in social behavior. To establish the relationship between anxiety and the outcome of a social competition, male outbred rats were first classified as high- intermediate- or low-anxious based on natural variation for anxiety-like behavior on the elevated plus maze Fig.Cell - The Unit of Life - Mitochondria - Structure - Part - 1
Their anxiety profiles were confirmed in another validated test for anxiety, the light—dark box Fig.