Understanding how molecules and mobile structures on the microfluidic cause communication between brain areas at the macroscale is a long-term goal of biology. For the first time in human history, a study has discovered hundreds of mind proteins that account for efficient connectivity and architectural covariation differences between individuals.
Understanding how molecules and biological structures on the microfluidic cause communication between brain areas at the macroscale is a long-term goal of biology. For the first time, a study published in Nature Neuroscience identifies hundreds of mind proteins that account for mortal brain structural and functional variations.
According to Jeremy Herskowitz, Ph. D.,” a key goal of science is to discover the brain that ultimately accounts for the mechanistic foundation of human consciousness and conduct.” PhD, associate professor in the Department of Neurology at the University of Alabama at Birmingham, and co-author of the research with Chris Gaiteri, Ph. D., SUNY Upstate Medical University, Syracuse, New York. This research demonstrates the utility of combining data from a variety of physiological scales to provide a chemical understanding of brain function.
The Catholic Orders Study and Rush Memory and Aging Project, or ROSMAP, at Rush University in Chicago, Illinois, made it possible to bridge the gap between the chemical level of proteins and mRNA and the brain-wide imaging level of efficient and architectural magnetic resonance imaging, which is roughly seven orders of magnitude.
ROSMAP enrolls Catholic sisters, priests and boys age 65 or older, who are without known memory at time of enrollment. Members agree to donate their neurons after they pass away and undergo annual medical and psychological assessment.
Herskowitz, Gaiteri and colleagues studied autopsy head examples and information from a unique group of 98 ROSMAP members. The resting state fMRI, architectural MRI, genetics, terminal spine morphometry, proteomics, and gene expression data were collected from the brain’s outstanding front and poor historical gyrus.
We hypothesized that postmortem chemical and subcellular information with postmortem neuroscience data from the same individuals could help promote the molecular mechanisms underlying mental communication, Herskowitz said.
The average age of the ROSMAP participants at time of MRI scan and at death were 88 + /- 6 years and 91 + /- 6 years, respectively, with an average time interval between the MRI scan and age at death of 3 + /- 2 years. The average postmortem interval to brain sampling was 8.5 + /- 4.6 hours. The researchers integrated the various data types using computational clustering algorithms after performing thorough analysis of each omic, cellular, and neuroimaging data type.
The research’s use of dendritic spine morphometry, the shapes, sizes, and densities of the spines as an intermediary scale measurement was crucial for linking the molecular scale with the brain-wide neuroimaging scale. For the detection of protein associations with functional connectivity, dendritic spine morphometry was required to contextualize the proteomic and transcriptomic signals. ” Initially, the protein and RNA measures could not explain the person-to-person variability in functional connectivity, however, it all clicked once we integrated the dendritic spine morphology to bridge the gap from molecules to inter-brain region communication”, Herskowitz said.
A dendrite is a branched extension of a neuron body that receives neuron impulses from other neurons. There are countless small spines that can protrude from a dendrite to a dendrite. To receive an impulse from one neuron’s axon, the head of each spine can form a contact point known as a synapse. The head of the spine supports postsynaptic density, and dementia spines can rapidly change shape or volume while creating new synapses, a process known as brain plasticity. Spines can be divided into shape subclasses based on their three-dimensional structure as thin, mushroom, stubby or filopodia. Herskowitz and colleagues used ROSMAP samples this summer to demonstrate that the quality of memory preserved in the very old when measured by the dendritic spine head diameter, not the number of synapses in the brain.
The hundreds of proteins that the researchers identified in this most recent study were enriched for those involved in synapses, energy metabolism, and RNA processing, which explain interindividual differences in functional connectivity and structural covariation. ” By integrating data at the genetic, molecular, subcellular and tissue levels, we linked specific biochemical changes at synapses to connectivity between brain regions”, Herskowitz said.
Overall, Herskowitz said,” This study shows that obtaining data from the same set of brains from the major perspectives in human neuroscience is essential to understanding how human brain function is supported by multiple biophysical scales.” We have established a robustly defined initial set of molecules whose effects likely extend across biophysical scales, despite the need for further investigation to fully understand the nature and components of multi-scale brain synchrony.
Besides Herskowitz and Gaiteri, co-authors of the study,” Multiscale Integration Identifies Synaptic Proteins Associated with Human Brain Connectivity”, are Bernard Ng, Shinya Tasaki and David A. Bennett, Rush University Medical Center, Chicago, Illinois, Kelsey M. Greathouse, Courtney K. Walker, Audrey J. Weber, Ashley B. Adamson, Julia P. Andrade, Emily H. Poovey, Kendall A. Curtis and Hamad M. Muhammad, UAB Department of Neurology and Center for Neurodegeneration and Experimental Therapeutics, Ada Zhang, SUNY Upstate Medical University, Sydney Covitz, Matt Cieslak, Jakob Seidlitz, Ted Satterthwaite and Jacob Vogel, University of Pennsylvania, Philadelphia, Pennsylvania, and Nicholas T. Seyfried, Emory University School of Medicine, Atlanta, Georgia.
Support came from National Institutes of Health grants AG061800, AG061798, AG057911, AG067635, AG054719, AG063755, AG068024, NS061788, AG10161, AG72975, AG15819, AG17917, AG46152 and AG61356.
At UAB, Neurology is a department in the Marnix E. Heersink School of Medicine.
