Neuro-diversity and "Neuronal Hyper-excitability"

Val's Take/Conjecture

One of the things that has happened in the last 15 years or so ---- we view these Neuro-Developmental and Psychiatrictric Disorders as much more blurred and having common mechanism.

We are also seeing the common mechanisms among:

• Neuro-Developmental and Psychiatric Disorders
• Autoimmune Disorders such as Multiple Sclerosis
  • "Genome-wide association studies reveal shared genetic haplotypes of autoimmune rheumatic and endocrine diseases with psychiatric disorders."
• Endocrine Disorders
  • "Most endocrine disorders are associated with psychological disturbances, and, conversely, psychiatric entities induce changes in hormonal activity, as is the case for adrenal and thyroid hormones."
• Metabolic Disorders such as Diabetes
  • "Dysregulation of immune and metabolism pathways in maternal immune activation induces an increased risk of autism spectrum disorders"
• Neuro-Degenerative Disorders such as Parkinson's and Alzheimers
  • Pathophysiological Role of Neuroinflammation in Neurodegenerative Diseases and Psychiatric Disorders
• Cancer
  • Mental Health America and Cancer

Deletion of TRPC6, an Autism Risk Gene, Induces Hyperexcitability in Cortical Neurons Derived from Human Pluripotent Stem Cells. (2023)

"ASD often co-occurs with attention-deficit hyperactivity disorder and epilepsy, which are associated with hyperexcitability of neurons.

"...Our data provide evidence that reduction of SOCE by TRPC6 KO results in neuronal hyperexc …"

Bright, but allergic and neurotic? A critical investigation of the "overexcitable genius" hypothesis. (2022)

"Individuals at the upmost end of the intelligence distribution are reported to be disproportionately afflicted by a set of stress-related physical and mental health conditions: so-called overexcitabilities.

"Few accounts have investigated this issue and no studies are avail …"

Potential of GABA-ergic cell therapy for schizophrenia, neuropathic pain, and Alzheimer's and Parkinson's diseases. (2016)

"Several neurological and psychiatric disorders present hyperexcitability of neurons in specific regions of the brain or spinal cord, partly because of some loss and/or dysfunction of gamma-amino butyric acid positive (GABA-ergic) inhibitory interneurons."

Intergenerational Metabolic Syndrome and Neuronal Network Hyperexcitability in Autism.  (2019)

"Maternal insulin resistance, obesity, and diabetes may predispose offspring to ASD by mechanisms involving chronic activation of anabolic cellular pathways and a lack of metabolic switching to ketosis resulting in a deficit in GABAergic signaling and neuronal network hy …"

Disruption of the Na(+)/K(+)-ATPase-purinergic P2X7 receptor complex in microglia promotes stress-induced anxiety.  (2024)

"Accordingly, global deletion or conditional deletion of NKAalpha1 in microglia under chronic stress-induced aggravated anxiety-like behavior and neuronal hyperexcitability.

"DR5-12D, a monoclonal antibody that stabilizes membrane NKAalpha1, improved stress-ind …"

Rod-shaped microglia interact with neuronal dendrites to regulate cortical excitability in TDP-43 related neurodegeneration. (Preprint, July 2024)

"Notably, rod-shaped microglia predominantly interact with neuronal dendrites and excitatory synaptic inputs to attenuate motor cortical hyperactivity.

"The elimination of rod-shaped microglia through TREM2 deficiency increased neuronal hyperactivity, ex …"