Didn't your competent? doctor start planning on how to use nogo receptor blockades 7 years ago?
Nogo receptor blockade overcomes remyelination failure after white matter stroke and stimulates functional recovery in aged mice December 2016
I guess your doctor knows nothing and does nothing! Why haven't they been fired yet? The board of directors is so fucking incompetent they haven't put 100% recovery goals for the whole stroke department!
Send me hate mail on this: oc1dean@gmail.com. I'll print your complete statement with your name and my response in my blog. Or are you afraid to engage with my stroke-addled mind? No excuses are allowed! You're medically trained; it should be simple to precisely refute all my points with NO EXCUSES!! And what is your definition of competence in stroke? Swearing at me is allowed, I'll return the favor.
On the Stability of Dendritic Architecture: Roles of Nogo Receptor 1 and Sleep
Thesis for Doctoral Degree (Ph.D.)
By
Alvin T.S. Brodin
The thesis will be defended in public at Clarence Crafoord A5:04, NKS, Eugeniavägen 3
Solna, Friday 14th of February 2025, 9.00 am
Principal Supervisor:
Dr Tobias Karlsson
Karolinska Institutet
Department of Neuroscience
Co-supervisor(s):
Professor Lars Olson
Karolinska Institutet
Department of Neuroscience
Opponent:
Dr Marta Zagrebelsky
TU Braunschweig
Zoological Institute
Division of Cellular Neurobiology
Examination Board:
Professor John Axelsson
Karolinska Institutet
Department of Clinical Neuroscience
Dr Jonathan Cedernaes
Uppsala University
Department of Medical Sciences
Professor Abdel el Manira
Karolinska Institutet
Department of Neuroscience
Abstract
The ability of the brain to rewire itself is central to its functioning. This plasticity
must be tightly regulated to ensure the stability of memories and maintain
normal levels of signalling. This thesis investigates two different systems
contributing to the regulation of structural plasticity.
Nogo receptor 1 (NgR1) is a potent negative regulator of plasticity. First
characterised in the setting of central nervous system injury, it is emerging as an
important regulator of memory formation as well. Understanding how this
system functions and is regulated could offer novel avenues for treatment of
common and severe brain diseases.
In paper I we investigated how Nogo receptor 1 levels influence memory function
and structural plasticity. Using transgenic mice, we found that constitutive
overexpression of NgR1 impaired performance in the Morris water maze, while
constitutive lack of NgR1 impaired novel object recognition. Further,
overexpression of NgR1 limited the formation of dendritic spines. This paper adds
to the growing evidence for a role for NgR1 in regulating memory formation and
structural plasticity.
Given that NgR1 is strongly expressed in highly plastic brain regions, we
hypothesised that there must be ways to bypass the growth inhibition of NgR1 to
allow for lasting memory formation. In paper IV we find that a chemical LTP
protocol induces rapid downregulation of dendritic NgR1 protein. Conversely, a
chemical LTD protocol rapidly upregulates dendritic NgR1 protein. These findings
suggest novel ways in which NgR1 levels are dynamically regulated to permit or
inhibit memory formation.
Sleep is a well-conserved and costly behaviour, yet its function remains poorly
understood. The synaptic homeostasis hypothesis is an influential theory that
proposes that sleep serves to downscale synaptic weights, and several lines of
evidence point to plastic changes in dendritic structure occurring during sleep.
However, the evidence is conflicted regarding whether sleep results in a net
growth or shrinkage of the dendritic tree. This is an important question to
elucidate if we are to develop effective treatments for the ill effects of sleep loss.
In paper II we investigated how CA1 dendritic structure is affected by sleep
deprivation. We measured dendritic length and dendritic spine density after 5 h
sleep deprivation by gentle handling, and did not find any significant effects. Inpaper III we looked at the same issue but through a systematic review and meta-
analysis. We included 30 studies in the meta-analysis, which were individually
small and with high variability We found that current evidence does not indicate
an effect on CA1 dendritic structure after 24 h or less of sleep deprivation.
Chronic sleep deprivation of 72 h or longer does reduce CA1 spine density and
dendritic length, but it remains unclear if this is solely due to sleep loss or to
stress associated with the method of sleep deprivation.
Together, these studies advance our understanding of how structural plasticity is
regulated.
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