Disease relevance of Retrograde Degeneration

• Increased knowledge of the UPS in synaptic and axonal reactions may provide novel drug targets for treatments of neuronal injuries and neurodegenerative disorders [1].
• These findings identify the probable target site for pyridoxine toxicity, and establish a simple animal model for studying not only sensory denervation, but also the axonal reaction and secondary degeneration [2].
• The non-fluorescent substance 1,2-diaminoanthraquinone (DAA) was injected into the eyes of rats whose optic nerve was injured to induce retrograde degeneration of the ganglion cells [3].
• Subsequent histological examinations showed that cortical infarction and retrograde degeneration of the ipsilateral thalamic neurons in ischemic rats infused with CNTF were significantly less severe than those in ischemic rats infused with vehicle alone [4].
• For example, after brain trauma mexidol strengthened compensatory-restorative processes: animals showed accelerated recovery of impaired functions, with decreases in the rate of retrograde degeneration of brain areas directly connected to the damaged parts, phenomena such as Monakow diaschisis were not observed, and so on [5].

Psychiatry related information on Retrograde Degeneration

• Evidence for retrograde degeneration of epinephrine neurons in Alzheimer's disease [6].
• These findings suggest that postischemic CNTF treatment prevents the occurrence of spatial learning disability in rats with permanent MCA occlusion, possibly by reducing neuronal damage within the cerebral cortex and secondary retrograde degeneration of the thalamus [4].

High impact information on Retrograde Degeneration

• Thus, the pmn gene mutation provides the first genetic evidence that alterations in tubulin assembly lead to retrograde degeneration of motor axons, ultimately resulting in motoneuron cell death [7].
• Results indicate that VP treatment following neurohypophysectomy results in extensive retrograde degeneration of magnocellular VP neurons without affecting the survival of OT cells [8].
• The absence of succinate dehydrogenase staining may reflect early changes in retrograde degeneration of thalamic neurons after ischemic injury of the thalamocortical pathway [9].
• In contrast to theories that the cell loss in MBN represents retrograde degeneration due to axonal injury in the cerebral cortex, MBN neuronal perikarya may be involved by the same primary processes as cortical neurons [10].
• Effects of pinealectomy and melatonin on the retrograde degeneration of retinal ganglion cells in a novel model of intraorbital optic nerve transection in mice [11].

Chemical compound and disease context of Retrograde Degeneration

• The present results thus indicate that exogenous GM1 enhances regrowth of noradrenaline nerve terminals which may be due to a regrowth stimulatory effect (regeneration/collateral sprouting) and/or related to protective actions of GM1 against retrograde degeneration of noradrenaline axons following the neurotoxin-induced lesion [12].
• Neurotoxic chemicals commonly produce retrograde degeneration of the axons of long and large nerve fibers in the central and peripheral nervous system [13].
• The partial response to hydroxyamphetamine in the two cases presented may reflect trans-synaptic degeneration of the postganglionic neuron [14].
• Loss of the immunoreactivity of tyrosine hydroxylase in perikarya may represent a retrograde axonal reaction, a potentially reversible response [15].
• The similarity in binding patterns between [(125)I] CGP42112 and [(3)H] PK11195 was shown to be primarily due to retrograde degeneration in the ipsilateral NTS, DMX and n.amb, as both radioligands were localized to similar cellular targets within the interstial space and over cellular debris [16].

Biological context of Retrograde Degeneration

• The time course for the loss of receptors is compatible with retrograde degeneration and suggests that specific benzodiazepine binding sites are in part located on mitral cell-bodies [17].
• In the present study, we examined this relationship for one component of the axon reaction (i.e. aberrant neurofilament (NF) phosphorylation) in the C57BL/Ola (Ola) mouse mutant, a model which exhibits delayed Wallerian degeneration (up to 3 weeks) and retarded regeneration of sensory neurons [18].
• Moreover, a site-specific generation of cytotoxic .OH free radicals and quinone/semiquinone radicals in the striatum may cause the observed lipid peroxidation, calcium overload, and retrograde degeneration of nigrostriatal neurons [19].

Anatomical context of Retrograde Degeneration

• The effects of pinealectomy and of intraperitoneally administered melatonin on the retrograde degeneration of retinal ganglion cells (RGCs) were examined in a novel model of optic nerve (ON) transection in C57BL/16J mice [11].
• Glutathione and glutathione S-transferase in the rainbow trout olfactory mucosa during retrograde degeneration and regeneration of the olfactory nerve [20].
• Rubrospinal tract cells undergo massive retrograde degeneration following spinal cord damage in newborn rats (Prendergast and Stelzner, J. Comp. Neurol. 166:163-172, '76b) [21].
• The present lesion model with an intense axon reaction and extensive nerve cell death does not seem to respond to administration of exogenous GM1 or thyrotropin-releasing hormone [22].
• Parenterally administered GM1 ganglioside prevents retrograde degeneration of cholinergic cells of the rat basal forebrain [23].

Gene context of Retrograde Degeneration

• To determine the subcellular mechanism underlying retrograde degeneration, the distribution of PNMT between axon terminal and cell body was calculated in early and advanced Alzheimer cases compared with age-matched controls [24].
• We also observed focal patches of hyper-phosphorylated NF and/or PHF/tau within APP-immunopositive dystrophic neurites, which appeared similar to retrograde degeneration, whereas we never observed focal accumulations of APP within NF- or PHF/tau-positive fibers [25].
• The prevention of the decrease of choline acetyltransferase (ChAT) enzymatic activity was achieved by applying GM1 in an animal model for studying retrograde degenerations of cholinergic neurons [26].
• After a 2-mm coronal incision was made in the cerebral cortex of adult rats, cholinergic axonal reaction and growth were assessed by acetylcholinesterase histochemistry between 3 and 56 days postinjury [27].
• Axon injury within the MS lesion will result in both Wallerian degeneration of the axon and also retrograde degeneration of the cell body [28].

Analytical, diagnostic and therapeutic context of Retrograde Degeneration

• A second experiment demonstrated that oral dosing with U-74006F (30 mg/kg), when limited to the first 5 days after axotomy, also significantly blunted retrograde degeneration measured at 21 days post-axotomy [29].
• Our observations also suggest that post-synaptic nerve degeneration (denervation) plays an important role in the increased sensitivity of the detrusor muscle to acetylcholine in the parasympathetically decentralized urinary bladder, whether denervation is due to trans-synaptic degeneration or impairment of micturition [30].

References