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  • Inflammation, the Immune System, Neuro-Developmental Disorders, Psychiatric Disorders, Substance Use Issues & Chronic Disease
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Metabolic and Innate Immune Cues Merge into a Specific Inflammatory Response via the UPR

A hodgepodge of thoughtS, Studies & concerns

Neuro-developmental Inflammation and Metabolic Dysregulation


Val's Take
 
             If we solve the "Mental Illness" puzzle we will likely solve the Obesity Epidemic.
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The vagus nerve and the inflammatory reflex--linking immunity and metabolism (2012)
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From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways (2016)

Abstract

The human body hosts an enormous abundance and diversity of microbes, which perform a range of essential and beneficial functions.

Our appreciation of the importance of these microbial communities to many aspects of human physiology has grown dramatically in recent years.

We know, for example, that animals raised in a germ-free environment exhibit substantially altered immune and metabolic function, while the disruption of commensal microbiota in humans is associated with the development of a growing number of diseases.

Evidence is now emerging that, through interactions with the gut-brain axis, the bidirectional communication system between the central nervous system and the gastrointestinal tract, the gut microbiome can also influence neural development, cognition and behaviour, with recent evidence that changes in behaviour alter gut microbiota composition, while modifications of the microbiome can induce depressive-like behaviours.

Although an association between enteropathy and certain psychiatric conditions has long been recognized, it now appears that gut microbes represent direct mediators of psychopathology.

Here, we examine roles of gut microbiome in shaping brain development and neurological function, and the mechanisms by which it can contribute to mental illness.

Further, we discuss how the insight provided by this new and exciting field of research can inform care and provide a basis for the design of novel, microbiota-targeted, therapies.
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A Sentinel in the Crosstalk Between the Nervous and Immune System: The (Immuno)-Proteasome (2019)

Abstract

The wealth of recent evidence about a bi-directional communication between nerve- and immune- cells revolutionized the traditional concept about the brain as an "immune-privileged" organ while opening novel avenues in the pathophysiology of CNS disorders.

In fact, altered communication between the immune and nervous system is emerging as a common hallmark in neuro-developmental, neurodegenerative, and neuro-immunological diseases.

At molecular level, the ubiquitin proteasome machinery operates as a sentinel at the crossroad between the immune system and brain.

In fact, the standard proteasome and its alternative/inducible counterpart, the immunoproteasome, operate dynamically and coordinately in both nerve- and immune- cells to modulate neurotransmission, oxidative/inflammatory stress response, and immunity.

When dysregulations of the proteasome system occur, altered amounts of standard- vs. immune-proteasome subtypes translate into altered communication between neurons, glia, and immune cells.

This contributes to neuro-inflammatory pathology in a variety of neurological disorders encompassing Parkinson's, Alzheimer's, and Huntingtin's diseases, brain trauma, epilepsy, and Multiple Sclerosis.

In the present review, we analyze those proteasome-dependent molecular interactions which sustain communication between neurons, glia, and brain circulating T-lymphocytes both in baseline and pathological conditions.

The evidence here discussed converges in that upregulation of immunoproteasome to the detriment of the standard proteasome, is commonly implicated in the inflammatory- and immune- biology of neurodegeneration.

These concepts may foster additional studies investigating the role of immunoproteasome as a potential target in neurodegenerative and neuro-immunological disorders.
Free Online Exercise Classes
Anti-Inflammatory Diet
We think Diet & Exercise are important.  But we don't want a situation in which other important factors are not considered as well.
Greg Doucette (Feb. 2020)
​​
Metabolism Doesn't Matter - Why Having A Fast Or Slow Metabolism Does NOT Determine Your Body Fat

----Your Ability to Suffer Matters, TRAIN HARDER

The over-the-top and very fun Greg Doucette probably does have a lot to teach us --- BUT it certainly appears there's even more to the story.

There are some professionals that are not that far from Greg Doucette and that's really a problem because ---
  • Nutrition & Exercise are going to be two of several keys to lower inflammation (but it may not be enough and for people with significant neuro-developmental inflammation our BELIEF is --- it's probably not going to be enough),
  • For some people with some type of Neuro-Developmental Disorder --- they're the ADHD Michael Phelps, maybe still struggling with mental health problems BUT in FANTASTIC SHAPE
  • For some men and a lot of women, they have thyroid disorders and neuro-developmental dysregulation of the metabolism as well as mental health issues.
    • ​There are often sex differences in ADHD with regard to who is gaining weight and one could SURMISE or CONJECTURE that this is EVOLUTIONARILY-based on an environment of scarcity --- which is NOT the Modern Environment.    

BUT SEE:

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Exercise Reverses Behavioral and Synaptic Abnormalities after Maternal Inflammation (2019)

Abstract

Abnormal behaviors in individuals with neurodevelopmental disorders are generally believed to be irreversible.

Here, we show that voluntary wheel running ameliorates the abnormalities in sociability, repetitiveness, and anxiety observed in a mouse model of a neurodevelopmental disorder induced by maternal immune activation (MIA).

Exercise activates a portion of dentate granule cells, normalizing the density of hippocampal CA3 synapses, which is excessive in the MIA-affected offspring. The synaptic surplus in the MIA offspring is induced by deficits in synapse engulfment by microglia, which is normalized by exercise through microglial activation.

Finally, chemogenetically induced activation of granule cells promotes the engulfment of CA3 synapses.

Thus, our study proposes a role of voluntary exercise in the modulation of behavioral and synaptic abnormalities in neurodevelopmental disorders.

Mixed Bags & the Proof is In the Pudding
  • anti-inflammatory diets and exercise are important and I think they will generally "Help."
  •  BUT THEY ARE CLEARLY NOT ALWAYS "HELPING" ENOUGH
  • There are A LOT of things -- that can "HELP."  There are more than 10 general areas to be explored:
    • ​Diet
    • Exercise
    • Work --- with Work Arounds and Accommodations for Executive Functioning if needed
    • Traditional Psychiatric Medication
    • Talk Therapy
    • Microbiome Therapy
    • Immuno Therapy
    • SLEEP
    • ​Nature
    • Art & Humanities
    • Science
    • Animal Assisted-Therapy

I think all these things can "HELP" and should be explored.

At the end of the day, some of us are STILL NOT NEURO-TYPICAL & our METABOLISM's aren't TYPICAL either--- and there has to be SPACE to say that.

NOT just WORK HARDER.

[In fairness, Greg Doucette might not recognize the problem of a slow metabolism as any real barrier to weight loss, but he does note the problem of "Sh---tty Genes."]


The more we understand Mental Health and Metabolic Dysregulation through a PRECISION MEDICINE PERSPECTIVE --- the better off a lot of us are going to be.

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  • Home
    • About Orchid >
      • Why Orchid?
      • ORCHID'S SYSTEMIC FOCUS & "ROOT CAUSE" ANALYSIS APPROACH TO PROBLEM SOLVING WITH A COMMITMENT TO CREATIVITY & INNOVATION
      • Disclaimers, Limitations and An Invitation
      • Orchid Board
      • Orchid Book Club
      • Conjecture, Science & Translational Research & Medicine
      • Orchid Themes & Symbols
      • The Tipping Point
      • Orchid's Website Advertising Policy
      • Statement for Potential Website Contributors
      • Contact
  • Blogs
    • Val's Blog
    • Val's Blog 2
    • ​TRANSLATIONAL/ ​TRANSITIONAL JUSTICE MONDAY
    • NEURO-DIVERSITY Wednesday
    • Olmstead Law & Order Thursday
    • Translational Medicine Friday
    • Translational Love, Relationships & Neuro-Diversity Saturday
  • Orchid's A-Z Index
    • Crisis Services in CO, the US & Around the World
    • Assertive Community Treatment & Flexible ACT Index
    • Housing & Homelessness Index
    • Criminal Justice
    • Innovation Index
    • For More: See the Main Orchid Index Page
  • US Federal
    • THE IMD RULE & ADMIN. ENFORCEMENT OF DISABILITY CIVIL RIGHTS LAWS
    • Medicaid & Supportive Housing & Housing-Related Services
    • CMS' FAILURE TO COVER HOUSING FOR LTC & THE IMD RULE: WHAT THEY HAVE IN COMMON IS DISCRIMINATION
    • National Take
  • Research & Translational Medicine
    • Immunology & Mental Health >
      • Alcoholism & the Immune System & Mental Health
      • Brain Injury, the Immune System & Mental Health
      • Celiac Disease & Sensitivities, the Immune System & Mental Illness
      • Mental Illness & The Immune System
      • Racial Discrimination & the Immune System & Mental Health
      • Trauma & the Immune System & Mental Health
      • ***Physical Health Issues, the Immune System & Mental Health Index
    • University of Chicago: Institute of Translational Medicine
  • Hot Topics
    • What We Want --- SAMHSA Grant Opportunities Due Jan. 22, 2019
    • Anti-Social Personality Disorder >
      • DECONSTRUCTING ANTISOCIAL PERSONALITY DISORDER AND PSYCHOPATHY: A GUIDELINES-BASED APPROACH TO PREJUDICIAL PSYCHIATRIC LABELS [Hofstra Law Review 2013]
      • Personality Disorders -- Unscientific & Vague -- Must Be Reformed
    • Executive Functioning & "Prison Brain" >
      • Job Accommodation Network on Executive Functioning Deficits
    • Medicaid & Medicare Network Adequacy >
      • OIG: STATE STANDARDS FOR ACCESS TO CARE IN MEDICAID MANAGED CARE (Sept. 2014)
      • OIG: ACCESS TO CARE: PROVIDER AVAILABILITY IN MEDICAID MANAGED CARE (Dec. 2014)
      • GAO 15-710: MEDICARE ADVANTAGE: Actions Needed to Enhance CMS Oversight of Provider Network Adequacy (Aug. 2015)
      • CMS: Promoting Access in Medicaid and CHIP Managed Care: A Toolkit for Ensuring Provider Network Adequacy and Service Availability (April 2017)
    • Medicaid Mental Health & Substance Use Disorder Parity >
      • CMS Parity Compliance Toolkit Applying Mental Health and Substance Use Disorder Parity Requirements to Medicaid and Children’s Health Insurance Programs [Jan. 17, 2017]
      • Frequently Asked Questions: Mental Health and Substance Use Disorder Parity Final Rule for Medicaid and CHIP [CMS October 11, 2017]
    • Olmstead Disability Rights >
      • Statement of the Department of Justice on Enforcement of the Integration Mandate of Title II of the Americans with Disabilities Act and Olmstead v. L.C. (2011)
      • Comprehensive Olmstead Planning
      • the Logical Long Term Consequences of our failure to provide Intensive Community MH Treatment
      • Olmstead Nation ---State Pages: How Far to Comply with Olmstead?
  • Take A Walk Around Orchid's Resource Block
  • Colorado Abuse & Neglect Scandals Involving People with Disabilities
  • Mental Health By The Numbers
  • New Science Is Amazing AND It Has HUGE Moral Implications for Our Society: NOW
  • Olmstead & Homelessness
  • Double V
  • " 'Defund the Police" Means 'Invest in the Resources Our Communities Need' " or Don't Cost Shift to the Police
  • VAGUE OLMSTEAD PLANS, EXPENSIVE LITIGATION
  • Updating & Reforming our Understanding & Treatment of "Anti-Social Personality Disorder" Blog
  • Reform of " Anti-Social Personality Disorder" in Criminal Justice
  • CO HB22-1278
  • New Understandings Matter
  • Mental Health, Ethics & Law
  • CO Olmstead Disability Homeless Law & Policy Project
  • Inflammation, the Immune System, Neuro-Developmental Disorders, Psychiatric Disorders, Substance Use Issues & Chronic Disease
  • Microglia and the Brain's Immune System
  • Substance Issues & the Immune System