Detrimental Physiological Effects of Microgravity on the Brain and DNA – Revised 2018-03-27T11:59:00+00:00

timthumb.php_

Detrimental Physiological Effects of Microgravity on the Brain and DNA
timthumb.php_

timthumb.php_

Microgravity imparts multiple deleterious effects on human physiology, which must be resolved as a prerequisite for enabling humans to engage in extended space expeditions.  A summary of these negative impacts on various physiological systems is listed in Table 1 below.  Nanomedicine might have the capacity to prevent or counteract the effects of microgravity (e.g., bone loss, neurological damage, soft tissue degradation, and detrimental ocular conditions to enable humans to endure prolonged missions to Mars and beyond, to the further reaches of deep space.timthumb.php_

System Microgravity Impact
Musculoskeletal System
  • Decreased bone formation
  • Increased bone resorption
  • Decreased bone mass
  • Decreased muscle mass
  • Decreased functional capacity
  • Increased muscle fatigue
  • Postflight muscle necrosis
Cardiovascular System
  • Reduced heart rate
  • Reduced diastolic pressure
  • Cardiac dysrhythmias
  • Headward fluid redistribution
  • Decreased plasma volume
  • Postflight hypovolemia
  • Postflight postural hypotension
Sensory Motor System
  • Deconditioning of posture and gait control
  • Deconditioning of motion sensors
  • Deconditioning of somatosensory system
  • Altered perception of orientation
  • Loss of balance
Immune System
  • Decreased number of T lymphocytes
  • Decreased response of T lymphocytes to potent activator
  • Reduced cytotoxic activity of natural killer cells
  • Alterations in cytokine/chemokine activity
Wound Healing
  • Impaired matrix formation
  • Impaired proliferation and migration of cells into wound
  • Reduced wound collagen content
  • Impaired revascularization
  • Impaired keratinocyte migration

Table 1: Physiological impacts of microgravity (reconfigured from Blaber, et al.)

Here, we briefly articulate what might be possible through the application of advanced nanomedicine toward addressing the deleterious effects of microgravity on other critical soft tissues, such as the brain, spinal cord, nervous system, and DNA. The functionality of degraded or destroyed populations of neurons and glial cells, as well as neuronal circuitry might be nanomedically restored through the use of targeted nanocarriers, which may precisely transport the appropriate molecules, biomaterials, and stem cells to any damaged sites of the nervous system to initiate efficacious repairs. Multilayered electrospun polymeric nanofiber scaffolds (Figure 1) may be self-assembled from constituent components in vivo and used to support the growth of stem cells. Nanofiber scaffolds comprised of electrospun polyvinyl alcohol (PVA)/chitosan nanofibers (~Ø 221 nm) were demonstrated by Alhosseini et al. to create microscale pores at their interstices, which facilitated cell tethering and migration, the proliferation of blood vessels, as well as to enable cellular nutrient and waste exchange.

timthumb.php_
Figure 1: Electrospun polycaprolactone (PCL) nanofiber scaffold (Image credit: Koh and Strange)

PC12 nerve cells from rat adrenal medulla were cultured on a PVA/chitosan nanofiber scaffold in vitro and observed to respond positively to the support. They also exhibited higher levels of attachment, propagation, migration, and viability in contrast to a pure PVA nanofiber scaffold. The presence of chitosan appeared to provide several physicochemical and biological factors that were amenable to the nerve cells including reduced nanofiber diameters, more surface resident amine and decreased water content. In a further neural engineering study by Jang et al., the growth of E18 rat hippocampal neurites traced the micropatterns of a substrate that were established by octadecyltrichlorosilane (OTS) and pristine carbon nanotubes (Figure 2), which biomimetically emulated extracellular matrices. It was suggested that a cell adhesion protein (poly-l-lysine (PLL)), which was coated onto the substrate, was a critical factor for attachment, guidance, and elongation.

timthumb.php_
Figure 2: Neuron networks (at seven divisions) shown on (a) carbon nanotube-only substrate and (b) patterned carbon nanotube/OTS substrate (Image credit: Jang et al.)

The nanomedical repair of the brain, at today’s level of sophistication, might involve the activation of renewable multipotent neural stem cells (NSCs) (Figure 3), as described by Santos et al., which reside within two specific regions of the brain (germinal subventricular and hippocampal subgranular zones), to rejuvenate neurons, astrocytes, and oligodendrocytes. The activation of NSCs might be initiated via the delivery of targeted nanoparticles that bear payloads of neurogenesis-inducing biomolecules to these sites, while imparting negligible side effects. (Reynolds and Weiss, Gage et al., Quadrato and Giovanni, Kazanis, Gage, Bible et al.)

timthumb.php_
Figure 3: Neural stems cells (Image credit: The New York Academy of Sciences)

Further in the future, with the advent of mature Molecular Manufacturing (MM), it might be possible to affect real time brain repairs almost instantaneously via sophisticated indwelling nanomedical devices. This strategy may sustainably negate the deleterious effects of both ionizing radiation and microgravity toward addressing the possibility of cumulative damage manifesting in the brain as the result of prolonged exposure to the space environment.

“A robust means for the preservation of the integrity and viability of DNA molecules and the proteins that they encode will be absolutely essential for long-haul human space travel and the eventual human habitation of the Moon, Mars, and beyond.” (Boehm) Within the nuclei of human cells (~Ø5-10 microns) there inherently exist a dozen species of protein based DNA repair mechanisms that are encoded by ~150 genes. Each of these self-assembling biological “nanomachines” is devoted to the repair of a specific type of damage to the DNA duplex. (Figure 4)

timthumb.php_
Figure 4: Illustration of deoxyribonucleic acid (DNA) (Image credit: Zephyris /Richard Wheeler)

In the space environment, microgravity in conjunction with ionizing radiation may negatively impact a number of DNA repair mechanisms. Subsequent to extensive studies of astronauts and cosmonauts it was revealed by Rowe that human exposure to microgravity induces a considerable decline in serum magnesium (Mg); an antioxidant and calcium blocker, which is critical for the binding of telomerase to DNA. Telomerase facilitates telomere elongation, chromosome stability, and the promotion of transcription and replication. Insufficient levels of magnesium results in oxidative stress, accelerated cell senescence, unstable DNA, as well as reduced protein synthesis and mitochondrial performance.

It was demonstrated that when human endothelial cells had no access to Mg for only two hours, they showed elevated levels of 8-hydroxy-deoxyguanine (in contrast to controls), which is a key DNA repair product that is generated in response to oxidative stress-induced DNA damage. To maintain ample concentrations of Mg under microgravity conditions, Mg loaded nanoparticles may have the capacity for the prolonged release of Mg ions, to sustain healthy plasma levels and those within intracellular compartments, which diminish over time and may not necessarily be related with concentrations in the plasma.

Svidinenko designed a conceptual sophisticated DNA repair nanorobot (Figure 5) that might transit along the duplex (similar to a bead on a chain). DNA damage would be detected immediately upon entering through the input port. When approaching the output port, the damaged DNA segment would be mechanically stabilized, where after the deficient base pairs would be removed and rapidly replaced by a dedicated “sequenator”, which could be considered as akin to the operation of a film-editing mechanism. The excised DNA segment would be then be discarded from a discharge port to be naturally degraded.

timthumb.php_
Figure 5: Conceptual DNA repair nanorobot (Image credit: Nanorobotmodels Medical Animation Studio)

News

Safety Panel Fears Soyuz Failure Could Exacerbate Commercial Crew Safety Concerns

October 16th, 2018|0 Comments

LAS CRUCES, N.M. — Members of an independent NASA safety panel said they were worried that the Oct. 11 Soyuz launch failure could make safety concerns with the agency's commercial crew program even worse. [...]

Canadian astronaut says human space travel will advance ‘sooner than you think’

October 15th, 2018|0 Comments

Canadian astronaut Col. Chris Hadfield (Ret.) on Friday said that human travel to space will happen sooner than we think, adding that the first destination will likely be a return trip to the moon. [...]

Ultrasmall targeted nanoparticles with engineered antibody fragments as an anti-cancer weapon

October 15th, 2018|0 Comments

Antibody-based imaging of a particularly aggressive form of breast cancer is undergoing clinical trials worldwide, but the path from trial to application is being hampered by a major obstacle: safety. Concerns stem from inefficient [...]

New Method Allows Harvesting of 2D Materials in Minutes

October 13th, 2018|0 Comments

Following the discovery of graphene in 2003, there has been considerable interest in other types of 2D materials. However, splitting a bulk crystal material into 2D flakes for use in electronics has proven hard [...]

Cybersecurity isn’t being taken seriously enough: MIT professor

October 10th, 2018|0 Comments

The digital economy is set to unlock tremendous economic value for countries over time. But a common setback for the use of various new technologies is their vulnerability to hackers. That's because companies and [...]

Other published works by Frank Boehm

October 9th, 2018|Comments Off on Other published works by Frank Boehm

Frank Boehm (NanoApps Medical CEO) and Angelika Domschke contributed the chapter : “Application of a Conceptual Nanomedical Platform to Facilitate the Mapping of the Human Brain: Survey of Cognitive Functions and Implications”. The book [...]

Nanomedical Device and Systems Design: Challenges, Possibilities, Visions now available to rent on Kindle

October 7th, 2018|0 Comments

To accommodate students who wish to read the book at an affordable cost, Nanomedical Device and Systems Design: Challenges, Possibilities, Visions by Frank Boehm (CEO NanoApps Medical Inc.) is available to rent on Kindle. This book benefits [...]

Why Cyber-Criminals Are Attacking Healthcare — And How To Stop Them

October 6th, 2018|0 Comments

The last five years has seen a surge of attacks on the healthcare industry, with the largest breaches impacting as many as 80 million people. In July this year, it was revealed that 150,000 [...]

A new era in the quest for dark matter

October 5th, 2018|0 Comments

Since the 1970s, astronomers and physicists have been gathering evidence for the presence in the universe of dark matter: a mysterious substance that manifests itself through its gravitational pull. However, despite much effort, none [...]

The Largest Event on Graphene Nanotubes is Open to the Public for the First Time

October 5th, 2018|0 Comments

The Nanoaugmented Materials Industry Summit (NAUM) 2018 in Shanghai on October 31 will gather the world’s leading companies who use and apply graphene nanotubes to share exciting results. This year the event is opening [...]

Simulations show new phenomenon with nanopore DNA sequencing

October 3rd, 2018|0 Comments

Any truck operator knows that hydraulics do the heavy lifting. Water does the work because it's nearly incompressible at normal scales. But things behave strangely in nanotechnology, the control of materials at the scale [...]

A human enzyme can biodegrade graphene

September 30th, 2018|0 Comments

Myeloperoxidase - an enzyme naturally found in our lungs - can biodegrade pristine graphene, according to the latest discovery of Graphene Flagship partners in CNRS, University of Strasbourg (France), Karolinska Institute (Sweden) and University [...]