Transneuronal degeneration in the Rolando substance of the primate spinal cord evoked by axotomy-induced transganglionic degenerative atrophy of central primary sensory terminals

Abstract

Transection of the sciatic nerve in Rhesus monkeys and the consequent transganglionic degenerative atrophy (TDA) of central terminals of primary afferents result in transneuronal degeneration of substantia gelatinosa (SG) cells. Severe degeneration is characterized by an increased electron density of the nucleus and by conspicuous shrinkage of the cytoplasm, mitochondrial swelling, dilation of cisterns of the rough-surfaced endoplasmic reticulum, accumulation of free ribosomes and an electron-dense material in the cytoplasm. In the mild form, dilation of cisternal elements of the endoplasmic reticulum, swollen mitochondria and accumulation of free ribosomes takes place. About 10% of SG cells in segment L5 undergo the severe form whereas the rest shows signs of the mild form. Cytoplasmic alterations that occur during transneuronal degeneration seem to start at the level of subsurface cisterns. Dendrites and axons of transneuronally degenerating SG cells also show a conspicuous electron density. By analyzing the synaptic relationships of such "darkened" dendrites, connections in the upper dorsal horn can be deciphered. Modular units of the primary nociceptive analyzer that evaluate noxious and innocuous inputs on the basis of thin versus thick (A delta C/A beta) afferent activity and subjecting them to descending control appear to be recruited from structurally dispersed elements of synaptic glomeruli. These are arranged alongside dendritic processes of large antenna cells which relay impulses to projection cells of the spinothalamic tract.

Early Withdrawal of Axons from Higher Centers in Response to Peripheral Somatosensory Denervation

“…Transneuronal atrophy of axons before it becomes manifest in somal shrinkage may also affect dorsal root ganglion cells after limb amputations or transections of nerves which sever the peripheral axons: in the long term, peripheral deafferentation causes extensive loss of dorsal root ganglion cells and of sensory axons entering the brainstem and spinal cord (Csillik et al, 1982; Knyihar-Csillik et al, 1987, 1989; Liss et al, 1996; Liss and Wiberg, 1997a, b), and transneuronal atrophy becomes detectable in neuronal somata in the cuneate nucleus and thalamus (Florence and Kaas, 1995; Jones and Pons, 1998; Woods et al, 2000) with a decrease in thalamic gray matter detectable by MRI in humans (Draganski et al, 2006). The atrophy of cuneate cell bodies will be accompanied by changes of the type we have described in their axons terminating in the thalamus and across the next synapse in the axons of deafferented thalamic relay neurons in the cortex.…”

A Critical Role of Toll-like Receptor 2 in Nerve Injury-induced Spinal Cord Glial Cell Activation and Pain Hypersensitivity

“…This implies the possibility that spinal cord glial cells are activated by injured axons even in the absence of neuronal cell death. Therefore, it is also conceivable that peripheral nerve injury may induce degeneration of central axons (57,58) and thereby induces activation of spinal cord glial cells via TLR2. During revision of the manuscript for this report it was reported that TLR2 is required for the hippocampal microglial activation due to axotomy of the entorhinal cortex (59).…”

Transneuronal Degeneration of Thalamic Nuclei following Middle Cerebral Artery Occlusion in Rats

“…The loss of function of neurons in the brain and spinal cord is known as neurodegeneration [1, 2]. Current research suggests that transneuronal degeneration plays a significant role in a number of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis [3–7]. …”

“…Transneuronal degeneration is also referred to as secondary neuronal degeneration and includes the following four stages: axonal transection, anterograde degeneration, retrograde degeneration, and associated neuronal degeneration [7]. In the human brain, the pathological processes induced by physical trauma or vascular blockages may cause neuronal damage, resulting in a disruption of axonal transmission in which both input and output information cannot be received by the associated neurons, following which anterograde and retrograde degeneration occur.…”