Blog Archives

Microglia, Neuro-Degenerative Diseases & Neuro-Developmental Disorders

1/31/2025

Dr. Melanie Capasso
DZNE, Bonn, Germany

Overactive Microglia in the Aging Brain

"Not only neurons exist in the brain, but also immune cells, the microglia. These microglia form our 'brain security' and protect the brain from pathogens.

"But with increasing age, the microglia, which are supposed to protect the brain, permanently raise the alarm and become chronically active.

"Inflammation occurs: this is an excessive immune reaction. The microglia turn against the brain and then secrete pro-inflammatory substances themselves.

"This violent over-activation in turn contributes to the progression of a neurodegenerative disease such as Alzheimer's – because inflammatory processes in the brain accelerate neurodegeneration, i.e. the death of neurons."

Lior Brimberg
Feinstein Institute for Medical Research

Captopril Reduces Microglial Activation in Autism and Improves Social Behavior

"As the primary brain immune cells, microglia are critical for maintaining a healthy brain and are recognized as important sculptors of neuronal development.

"Exposure in utero to maternal brain reactive antibodies may perturb microglia programing leading to neurodevelopmental disorder."

MiCROGLIA & Substance Use

1/25/2025

Val's Take/Conjecture

Neuro-Developmental Disorders and Substance Use Issues are very prevalent in the Criminal Justice System and have challenged reform efforts.
My big mantra has been --- we need A PUBLIC HEALTH APPROACH to CRIMINAL JUSTICE.
We need the updated understandings and treatments to fully make that a reality.
That is what the researchers are giving us.
Further, many of our current treatments are helping people.

Microglia NLRP3 Inflammasome and Neuroimmune Signaling in Substance Use Disorders. (2023)

"During the last decade,
substance use disorders (SUDs) have been increasingly recognized as neuroinflammation-related brain diseases.

...Recently, inflammasome-mediated signaling has been identified as playing critical roles in the microglia activation …"

Glial mechanisms underlying substance use disorders.
(2019)

"Although there is an extensive body of literature examining the neuronal mechanisms of substance use disorders, effective therapies remain elusive.

"Glia, particularly microglia and astrocytes, have an emerging and meaningful role in a variety of proces …"

New study shows adults with Autism Need More Support

1/24/2025

Val's Take: First, I think Taylor Heaton does such important work and she reaches so many people on YouTube.

I do want to say that the increase in Neuro-Developmental & Psychiatric Diagnoses is in part AWARENESS, but it's not just that.

Further, there is a great need for INTEGRATIVE THINKING to address the wicked problems of Giftedness/Sensory Processing Differences and Emotional Dysregulation in Neuro-Developmental & Psychiatric Disorders.

Additionally, Neuro-Developmental Disorders involve Developmental Inflammation and a kind of Premature Aging affecting multiple systems of the body resulting in Dysregulated Stress Responses and in many cases serious negative health consequences across the lifespan.

Taylor Heaton ---
Mom on the Spectrum
New Study Shows Adults with Autism Need More Support

Glial-Neuronal Networks & Neuro-Developmental & Psychiatric Disorders

1/20/2025

Val's Take: This video is from 14 years ago. The whole Glial, Neuron, Mental Health connection is "NEW" in a broad sense, but some researchers have been working on this for awhile --- and the number of researchers working on understanding the importance of Glial Cell Types in Neuro-Developmental and Psychiatric Disorders has increased exponentially over the last 5 years.

One of the points that Professor Hickie makes and I have tried to make although I'm not necessarily the best messenger for this --- we need to integrate Clinical and Research practice.

If you spend a lot of time trolling PubMed like I do --- there do seem to be big gulfs among the Researchers, the Clinicians and the Public with regard to basic understandings that greatly affect TREATMENT and POLICY.

Professor Ian Hickie, Brain Mind Centre (Australia)
Glial-Neuronal Networks: Dysfunction in Youth Mental Health

"Resilience," The Immune System & "Second Hits"

1/12/2025

Val's Take/Conjecture

"Maternal Immune Activation" involves the Immune System and occurs In Utero.
Among other things, Maternal Immune Activation impacts Adult Behavior.
So the first hit is "Maternal Immune Activation."
But during the course of our lives we have many and varied experiences of INFLAMMATION and STRESS.
It's a BRAVE NEW WORLD out there and some researchers are already proposing:
- "immunomodulatory" treatments for depression, and
- targeting microglia in treatment efforts.
The point I want to make is that when we talk about "RESILENCE" --- there are actually very complicated mechanics to that.

Additionally, UNPREDICTED CHRONIC STRESS seems to be an issue for mammals and us.

The Unpredictability of Neuro-Developmental and Psychiatric Disorders is taking a huge toll on Individuals, Families, Communities and Societies.
There is CONSCIOUS AWARENESS of the need for:
- Updated Paradigms
- Biomarkers, and
- Better Treatments that address Multi-System Disorders

Genes Participating in the Ensheathment of Neurons Are Affected by Postnatal Stress and Maternal Immune Activation in the Pituitary Gland (2023)

Fetal brain response to maternal inflammation requires microglia
(2024)

In utero infection and maternal inflammation can adversely impact fetal brain development.

Maternal systemic illness, even in the absence of direct fetal brain infection, is associated with an increased risk of neuropsychiatric disorders in affected offspring. . .

Using a rodent maternal immune activation (MIA) model in which polyinosinic:polycytidylic acid is injected into pregnant mice, we demonstrate long-lasting transcriptional changes in fetal microglia that persist into postnatal life.

We find that MIA induces widespread gene expression changes in neuronal and non-neuronal cells; importantly, these responses are abolished by selective genetic deletion of microglia, indicating that microglia are required for the transcriptional response of other cortical cell types to MIA.

These findings demonstrate that microglia play a crucial durable role in the fetal response to maternal inflammation, and should be explored as potential therapeutic cell targets.

The inflammatory underpinning of depression: An historical perspective (2024)

"Synthesizing insights from this extensive research, the review presents an integrative model of the biological foundations of inflammation-associated depression.

"It posits that we have reached a critical juncture where the translation of this knowledge into personalized immunomodulatory treatments for depression is not just possible, but imperative."

Microglial TREM 2 Gene

1/11/2025

*Neuro-Degeneration
*Cancer
*Neuro-Developmental Disorders &
*Psychiatric Disorders

TREM2 in Neuro-Degeneration

TREM2 regulates BV2 microglia activation and influences corticosterone-induced neuroinflammation in depressive disorders (2024)

TREM2 improves microglia function and synaptic development in autism spectrum disorders by regulating P38 MAPK signaling pathway (2024)

A multi-omics study of brain tissue transcription and DNA methylation revealing the genetic pathogenesis of ADHD (2024) [includes TREM2]

Trem2 expression in microglia is required to maintain normal neuronal bioenergetics during development (2024)

Engineered Microglia and More

1/10/2025

Val's Take/Conjecture

A collection of articles featuring:
- Engineered Microglia as a Treatment
- The Role of Glial Cells in Mental Illness
- Maternal Immune Activation Generates "Anxiety" in Offspring.
- ADHD as "Dysregulated not Deficit" and
- Maternal Type-I interferon signaling adversely affects Microglia resulting in increased Sensitivity to Stress.

This new research requires significant modification of our paradigms.

Taming microglia: the promise of engineered microglia in treating neurological diseases (2024)

The role of glial cells in mental illness: a systematic review on astroglia and microglia as potential players in schizophrenia and its cognitive and emotional aspects (2024)

Maternal immune activation generates anxiety in offspring (2021)

“Dysregulated not deficit”: A qualitative study on symptomatology of ADHD in young adults (2023)

Maternal Type-I interferon signaling adversely affects the microglia and the behavior of the offspring accompanied by increased sensitivity to stress (2019)

Addiction

1/5/2025

Val's Take: U2's "Bad" is from 1984. I actually didn't hear it until working on it this past year with the Ukulele and Percussion Ensemble at Swallow Hill Music in Denver.

It meant a lot more to me now than I think it would have meant to me in 1984.

It is about Addiction and how morally implicated and powerless the people witnessing that feel. You know you're not helping or solving things --- but you don't know what to do and there is GUILT.

To make matters even more morally fraught, it is not just you or Bono who are lamenting, "If I could, yes I would. If I could, I would" --- it is often the person themselves.

Further, you are NOT PERFECT --- maybe you don't have an illegal substance problem -- as you're guzzling your 7th Diet Coke of the day.

Further, your intended recipient of this angst might be grateful they don't have some of your problems -- "There but for the grace of God go I."

At the end of the day, this is about IMPERFECT PEOPLE HELPING IMPERFECT PEOPLE.

Dr. Mizra talks about the connection between ADHD & Substance Use Issues.

Dr. Sulman Aziz Mirza, MD is Board Certified physician in Adult Psychiatry, Child & Adolescent Psychiatry and Addiction Medicine.

Val's Take: Just as I think it is important to recognize the NEURO-DEVELOPMENTAL/PSYCHIATRIC CONTINUUM --- it is important to include SUBSTANCE USE ISSUES.

There are many aspects to that. Two of those aspects seem to include:

having enough ENERGY to run the brain and the synapses; and
dealing with AFFECTIVE PAIN that may be HIGHLY DYSREGULATED.

This is Neurobiologist David Anderson's 2013 TedTalk. He has a lab at Caltech bearing his name.

He is an amazingly accomplished researcher.

I've posted this video on Orchid several times for various purposes.

Here, he makes many salient points, including:

we need psychiatric medications that are precise and do not affect the brain globally.
Additionally, we need to understand the specific biology of various components of these disorders --- because they don't always go together.

Translational Medicine Friday

Microglia, Neuro-Degenerative Diseases & Neuro-Developmental Disorders

MiCROGLIA & Substance Use

New study shows adults with Autism Need More Support

Glial-Neuronal Networks & Neuro-Developmental & Psychiatric Disorders

"Resilience," The Immune System & "Second Hits"

Microglial TREM 2 Gene

Engineered Microglia and More

Addiction

Translational Medicine Friday

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