Blog Archives

Mitochondrial Dysfunction

3/31/2025

Val's Take: More and more Researchers are moving beyond DSM symptom clusters to INDIVIDUALIZED PRECISION MEDICINE and BIOLOGICAL MECHANISMS such as cell types, organelles, DNA, RNA, epigenetics, molecular pathways, the microbiome, the endocrine system, the immune system and yes the brain and the central nervous system and their relationships to each other trans-generationally, developmentally and over the life span.

My understanding is that it was Researchers and Clinicians addressing Orphan Mitochondrial Diseases that only effect a small number of people --- who started to point out that MOST DISEASE and DISORDER involve some type of Mitochondrial Dysfunction --- as it turns out they were right.

What I particularly appreciate about Dr. Madsen's video is that he appreciates the importance of Diet and Exercise while at the same time understanding that will often not be sufficient alone.

Additionally, Dr. Madsen as others are pointing out the significant role of modern Environmental Toxins --- which like Climate Change is hugely inconvenient.

Finally, the Reverse Aging Revolution folks understand that Mitochondrial Dysfunction ultimately affects everyone through the Aging Process ---- some of us sooner than others --- but Mitochondrial Dysfunction is of universal concern.

Unravelling the Brain with Dr. Josh Madsen
The Hidden Crisis of Autism & Mitochondrial Dysfunction Explained (2025)

Reverse Aging Revolution
Producing Young Mitochondria Accessible For Everyone - Mitochondrial Transplantation For Longevity (2024)

One thing leads to another

3/16/2025

Val's Take: "You told me something wrong --- I know I listen too long --- but one thing leads to another --- I know you been lying to me."

I don't think the Mental Health Profession has been "lying to me," but . . .

There are major problems that are not being addressed in this gap between the researchers and the clinicians.

Once we go from Neuro-Developmental and Psychiatric Disorders as Brain Disorders --- to Multi-System Neuro Immune Disorders --- that implicates other medical disciplines.

"The wrong antidote is like a bone in the throat."

The hard issues regarding the Shaky Foundation of Psychiatric Diagnostics

The DSM 5 and the Criminal Justice Wheel of Fortune

New Understandings Matter

Science Up

fetal microglia, inflammation & neuronal Hyper-excitoxicity in neuro-developmental & Psychiatric Disorders

3/8/2025

Val's Take/ Conjecture

It's more complicated than this --- but Microglia are essentially the Brain's Innate Immune Cells.
Maternal Immune Activation appears to effect adult behavior by among other things:
- Dysregulating Amoeboid Microglia during pregnancy. Those Amoeboid Microglia ultimately become
- Ramified Microglia in the Adult Central Nervous System

Astrocytes are another type of glial cell, different than Microglia.
Astrocytes do a number of things, including maintaining glutamate homeostasis.
Glutamate excitotoxicity is involved with Neuro-Developmental and Psychiatric Disorders.

Microglial contribution to the pathology of neurodevelopmental disorders in humans (2023)

Dysfunctional mitochondrial processes contribute to energy perturbations in the brain and neuropsychiatric symptoms (2023)

Glutamate-Mediated Excitotoxicity in the Pathogenesis and Treatment of Neurodevelopmental and Adult Mental Disorders (2024)

"In the current narrative review, we will summarize the role of glutamate-induced excitotoxicity in both the pathophysiology and therapeutic interventions of neurodevelopmental and adult mental diseases with a focus on autism spectrum disorders, substance abuse, and psychiatric disorders.

"Indeed, glutamatergic drugs are under preclinical and clinical development for the treatment of different mental diseases that share glutamatergic neuroplasticity dysfunctions."

"Our mission: to help accelerate the next breakthrough in drug discovery, diagnostics and basic research."

Microglia subtype markers
(2022)

Amoeboid microglia
- Amoeboid microglia are associated with the developing CNS. In rats, amoeboid microglia have been shown to appear late in gestation and disappear soon after birth.
- Ultimately, amoeboid microglia grow long crenulated processes and transform into ramified microglia found in the adult CNS.
Ramified microglia
Reactive microglia
- Like macrophages, reactive microglia secrete inflammatory mediators, which orchestrate the cerebral immune response.

Chronic microglial activation is associated with neurological disorders including Alzheimer's disease, multiple sclerosis, and delayed neuronal death occurring after ischaemia.

In these instances, the persistent activation of microglia accompanied by the sustained secretion of inflammatory mediators is thought to have a deleterious effect on neuronal function and survival, thereby exacerbating disease processes.

CD45 - microglia
CD45 - macrophage
CD11b
CD68 - microglia
CD68 - macrophage

Astrocytes Maintain Glutamate Homeostasis in the CNS by Controlling the Balance between Glutamate Uptake and Release (2019)

Metabolism & Maternal Immune activation

3/2/2025

Val's Take/Conjecture

One of many things making these insights hard to come by beyond the need for advanced technology is that Neuro-Diversity is characterized by DIVERSITY.
Further, METABOLIC DYSREGULATION is different in different people --- it doesn't necessarily look the same.

Dysregulation of immune and metabolism pathways in maternal immune activation induces an increased risk of autism spectrum disorders (2023)

Key findings: A novel evidence was proved that illustrated altering four immune and metabolism-related risk pathways, including starch and sucrose metabolism, ribosome, protein processing in endoplasmic reticulum, and retrograde endocannabinoid signaling pathway, which were prominent involvement in the process of MIA regulating abnormal fetal brain development to induce an increased risk of ASD.

Here, we have observed that almost all key genes within these risk pathways are significantly differentially expressed at embryonic days (E) 10.5-12.5, which is considered to be the optimal coincidence window of mouse embryonic brain development to study the intimate association between MIA and ASD using mouse animal models.

Significance: [The] search establishes that MIA causes dysregulation of immune and metabolic pathways, which leads to abnormal embryonic neurodevelopment, thus promoting development of ASD symptoms in offspring.

Shared genetic architecture and bidirectional clinical risks within the psycho-metabolic nexus (2025)

Interpretation: The study highlights the intertwined genetic and clinical relationships between psychiatric disorders and metabolic dysregulations, emphasizing the need for integrated approaches in diagnosis and treatment.

Molecular and metabolic heterogeneity of astrocytes and microglia (2023)

Abstract

Astrocytes and microglia are central players in a myriad of processes in the healthy and diseased brain, ranging from metabolism to immunity.

The crosstalk between these two cell types [Astrocytes & Microglia] contributes to pathology in many if not all neuroinflammatory and neurodegenerative diseases.

Recent advancements in integrative multimodal sequencing techniques have begun to highlight how heterogeneous both cell types are and the importance of metabolism to their regulation.

We discuss here the transcriptomic, metabolic, and functional heterogeneity of astrocytes and microglia and highlight their interaction in health and disease.

Translational Medicine Friday

We're riffing off NPR's Science Friday to create Translational Medicine Friday.

We'll be collecting Research Article recommendations for Clinicians with regard to Cognitive Disability.

There is much in the RESEARCH JOURNALS and we'll just be SKIMMING THE SURFACE.

The POINT is to INCREASE FUNDING for TRANSLATIONAL RESEARCH at the Federal Level for the National Institutes of Health, the Centers for Disease Control, the Nation's Research & Teaching Hospitals and possible collaborations with Medicare and Medicaid providers.

Translational Medicine Friday

Mitochondrial Dysfunction

One thing leads to another

fetal microglia, inflammation & neuronal Hyper-excitoxicity​ in neuro-developmental & Psychiatric Disorders

Metabolism & Maternal Immune activation

Translational Medicine Friday

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fetal microglia, inflammation & neuronal Hyper-excitoxicity in neuro-developmental & Psychiatric Disorders