This system is very complex.
The autonomic nervous system controls internal body processes such as the following:
- Blood pressure
- Heart and breathing rates
- Body temperature
- Metabolism (thus affecting body weight)
- The balance of water and electrolytes (such as sodium and calcium)
- The production of body fluids (saliva, sweat, and tears)
- Sexual response
All of these internal body processes are important and disruption of any of them can be important clues to the treatment of bipolar illness syndromes.
I would like to mention that, between Dr Kraepelin studies and ours [Paula and I], we found that ALL the functions listed above are disrupted during bipolar depressive and/or manic and/or mixed state attacks, in different patterns.
And what seems most puzzling is the “out of sync” behaviour of the ventilatory system, which, seems to run counter to what usually occurs during periods of extreme distress and fear which occurs in bipolar depressive states. [see previous blogposts describing experiences described by Kraepelin’s patients and by Paula during bipolar depression].
This “out of sync” behaviour on the part of the motor system of breathing makes no sense...in health…in illness…in depression…in mania [it is different in mania] ….in states of fear [while “at rest”…etc….it just makes no sense at all!
This tells us that the autonomic nervous system and especially the sympathetic nervous system are disrupted during bipolar attacks. I have already presented evidence that there seems to be ” impaired adaptation to common physiologic stressors” affecting the sympathetic nervous system response to certain kinds of metabolic stressors and that , in particular evidence shows that the skeletal muscles of the ventilatory system seem to have suffered damage.
The autonomic nervous system consists of the neurons of both the SNS [sympathetic nervous system] and the PNS parasympathetic nervous system].
Anatomically, the sympathetic preganglionic neurons, the cell bodies of which are located within the central nervous system, originate in the lateral horns of the 12 thoracic and the first 2 or 3 lumbar segments of the spinal cord. (For this reason the sympathetic system is sometimes referred to as the thoracolumbar outflow.) The axons of these neurons exit the spinal cord in the ventral roots and then synapse on either sympathetic ganglion cells or specialized cells in the adrenal gland called chromaffin cells. https://www.britannica.com/science/preganglionic-neuron
What is fascinating is that the research paper below presents evidence that “The sympathetic nervous system regulates skeletal muscle motor innervation and acetylcholine. and receptor stability” Acta Physiol (Oxf) 2019 Mar;225(3):e13195. doi: 10.1111/apha.13195. Epub 2018 Oct 22. https://pubmed.ncbi.nlm.nih.gov/30269419/
“The sympathetic nervous system regulates skeletal muscle motor innervation and acetylcholine and receptor stability
Anna C Z Rodrigues 1 2, Maria L Messi 1, Zhong-Min Wang 1, Martin C Abba 3, Andrea Pereyra 1, Alexander Birbrair 1, Tan Zhang 1, Meaghan O’Meara 1, Ping Kwan 1 2, Elsa I S Lopez 4, Monte S Willis 5, Akiva Mintz 6, D Clark Files 1 4 7, Cristina Furdui 4, Ronald W Oppenheim 8, Osvaldo Delbono 1 2 PMID: 30269419 PMCID: PMC7224611 DOI: 10.1111/apha.13195
Aim: Symptoms of autonomic failure are frequently the presentation of advanced age and neurodegenerative diseases that impair adaptation to common physiologic stressors. The aim of this work was to examine the interaction between the sympathetic and motor nervous system, the involvement of the sympathetic nervous system (SNS) in neuromuscular junction (NMJ) presynaptic motor function, the stability of postsynaptic molecular organization, and the skeletal muscle composition and function.
Methods: Since muscle weakness is a symptom of diseases characterized by autonomic dysfunction, we studied the impact of regional sympathetic ablation on muscle motor innervation by using transcriptome analysis, retrograde tracing of the sympathetic outflow to the skeletal muscle, confocal and electron microscopy, NMJ transmission by electrophysiological methods, protein analysis, and state of the art microsurgical techniques, in C57BL6, MuRF1KO and Thy-1 mice.
Results: We found that the SNS regulates motor nerve synaptic vesicle release, skeletal muscle transcriptome, muscle force generated by motor nerve activity, axonal neurofilament phosphorylation, myelin thickness, and myofibre subtype composition and CSA. The SNS also modulates the levels of postsynaptic membrane acetylcholine receptor by regulating the Gαi2 -Hdac4-Myogenin-MuRF1pathway, which is prevented by the overexpression of the guanine nucleotide-binding protein Gαi2 (Q205L), a constitutively active mutant G protein subunit.
Conclusion: The SNS regulates NMJ transmission, maintains optimal Gαi2 expression, and prevents any increase in Hdac4, myogenin, MuRF1, and miR-206. SNS ablation leads to upregulation of MuRF1, muscle atrophy, and downregulation of postsynaptic AChR. Our findings are relevant to clinical conditions characterized by progressive decline of sympathetic innervation, such as neurodegenerative diseases and aging.
Keywords: muscle denervation; muscle innervation; neuromuscular junction; skeletal muscle; sympathetic nervous system.
© 2018 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.
This is significant; given that that our ability breathe, to actually move air in and out of our [healthy lungs] depends on our skeletal muscle strength, which are dependent on sympathetic innervation, which can become damaged by injury, disease or age.
And if this happens to us at any age, then we will be less able to deal with the stress of the motor part of breathing air and be more at risk for respiratory acid base disorders such as hypercapnia which is a major but reversible metabolic stressor .
Ageing Res Rev
. 2021 May;67:101305.
doi: 10.1016/j.arr.2021.101305.Epub 2021 Feb 18.
The emerging role of the sympathetic nervous system in skeletal muscle motor innervation and sarcopenia
PMID: 33610815 PMCID: PMC8049122 (available on 2022-05-01) DOI: 10.1016/j.arr.2021.101305
Examining neural etiologic factors’role in the decline of neuromuscular function with aging is essential to our understanding of the mechanisms underlying sarcopenia, the age-dependent decline in muscle mass, force and power. Innervation of the skeletal muscle by both motor and sympathetic axons has been established, igniting interest in determining how the sympathetic nervous system (SNS) affect skeletal muscle composition and function throughout the lifetime. Selective expression of the heart and neural crest derivative 2 gene in peripheral SNs increases muscle mass and force regulating skeletal muscle sympathetic and motor innervation; improving acetylcholine receptor stability and NMJ transmission; preventing inflammation and myofibrillar protein degradation; increasing autophagy; and probably enhancing protein synthesis. Elucidating the role of central SNs will help to define the coordinated response of the visceral and neuromuscular system to physiological and pathological challenges across ages. This review discusses the following questions: (1) Does the SNS regulate skeletal muscle motor innervation? (2) Does the SNS regulate presynaptic and postsynaptic neuromuscular junction (NMJ) structure and function? (3) Does sympathetic neuron (SN) regulation of NMJ transmission decline with aging? (4) Does maintenance of SNs attenuate aging sarcopenia? and (5) Do central SN group relays influence sympathetic and motor muscle innervation?
Keywords: Aging; Autonomic nervous system; Denervation; Motoneuron; Neuromuscular junction; Sarcopenia; Skeletal muscle; Sympathetic nervous system.
Copyright © 2021 Elsevier B.V. All rights reserved.
Again, very relevant to the neuromuscular skeletal motor act of ventilation and air exchange to and from the lungs and the ratio of O2/CO2 so vital to respiratory acid base regulation of the body and the brain.
. 2015 Jul;95(3):809-52.
Mechanisms Regulating Neuromuscular Junction Development and Function and Causes of Muscle Wasting
PMID: 26109340 DOI: 10.1152/physrev.00033.2014
The neuromuscular junction is the chemical synapse between motor neurons and skeletal muscle fibers. It is designed to reliably convert the action potential from the presynaptic motor neuron into the contraction of the postsynaptic muscle fiber. Diseases that affect the neuromuscular junction may cause failure of this conversion and result in loss of ambulation and respiration. The loss of motor input also causes muscle wasting as muscle mass is constantly adapted to contractile needs by the balancing of protein synthesis and protein degradation. Finally, neuromuscular activity and muscle mass have a major impact on metabolic properties of the organisms. This review discusses the mechanisms involved in the development and maintenance of the neuromuscular junction, the consequences of and the mechanisms involved in its dysfunction, and its role in maintaining muscle mass during aging. As life expectancy is increasing, loss of muscle mass during aging, called sarcopenia, has emerged as a field of high medical need. Interestingly, aging is also accompanied by structural changes at the neuromuscular junction, suggesting that the mechanisms involved in neuromuscular junction maintenance might be disturbed during aging. In addition, there is now evidence that behavioral paradigms and signaling pathways that are involved in longevity also affect neuromuscular junction stability and sarcopenia.
Copyright © 2015 the American Physiological Society.
Wow!!! Could damage to the neuromuscular junction be the reason why Paula cannot raise her already too low breathing ventilatory rate during metabolic crisis and sympathetic activation?
Wow!!! Could this be the reason for the psychomotor retardation of bipolar depressive episodes and the psychomotor excitement of manic episodes?
Wow!! Who would have guessed? Who would have thought?
I know! Dr Emile Kraepelin would have guessed and did hypothesize such an idea, over 100 years ago right before his death.
Too bad he was not alive to be able to research this hypothesis further.
Too bad no one read his studies carefully.
Too bad, indeed!
to be continued……………..