Projection neurons and interneurons in the lateral geniculate nucleus undergo distinct forms of degeneration ranging from retrograde and transsynaptic apoptosis to transient atrophy after cortical ablation in rat

Al-Abdulla, Nael A.; Martin, Lee J.

doi:10.1016/s0306-4522(02)00363-9

Cited by 25 publications

(27 citation statements)

References 24 publications

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“…Ablation of cells within the primary visual cortex (V1) has been shown to lead to the retrograde degeneration of neurons in the LGNd (Lashley, 1941), therefore, such a loss of cells within the cerebral cortex might trigger cell loss in the LGNd. Whereas cortical ablation of V1 leads to degeneration of the large projection neurons within LGNd, the GABAergic interneurons within this thalamic nucleus are spared cell death (Al-Abdulla and Martin, 2002). Interestingly, the Cln3 −/− mice suffer selective loss of the large projection neurons with no loss in this small cell population.…”

Section: Discussionmentioning

confidence: 99%

Visual deficits in a mouse model of Batten disease are the result of optic nerve degeneration and loss of dorsal lateral geniculate thalamic neurons

Weimer

Custer

Benedict

et al. 2006

Neurobiology of Disease

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Juvenile neuronal ceroid lipofuscinosis (JNCL) is an autosomal recessive disorder of childhood caused by mutations in CLN3. Although visual deterioration is typically the first clinical sign to manifest in affected children, loss of Cln3 in a mouse model of JNCL does not recapitulate this retinal deterioration. This suggests that either the loss of CLN3 does not directly affect retinal cell survival or that nuclei involved in visual processing are affected prior to retinal degeneration. Having previously demonstrated that Cln3 −/− mice have decreased optic nerve axonal density, we now demonstrate a decrease in nerve conduction. Examination of retino-recipient regions revealed a decreased number of neurons within the dorsal lateral geniculate nucleus (LGNd). We demonstrate decreased transport of amino acids from the retina to the LGN, suggesting an impediment in communication between the retina and projection nuclei. This study defines a novel path of degeneration within the LGNd, providing a mechanism for causation of JNCL visual deficits.

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Section: Discussionmentioning

confidence: 99%

Visual deficits in a mouse model of Batten disease are the result of optic nerve degeneration and loss of dorsal lateral geniculate thalamic neurons

Weimer

Custer

Benedict

et al. 2006

Neurobiology of Disease

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“…Interestingly, two weeks after occlusion of MCA, the fMRI response to stimulation of the affected forelimb is shown to be absent in the ipsilateral thalamus although it can be detected in the ipsilesional cortex [57]. Changes in neuroplasticity occurs in the thalamus, where retrograde neuronal degeneration has been found after cortical damage [58]. However, to our knowledge there are no studies that examine how the age- and motionless-related rhythmical patterns like HVSs might be influenced by stroke.…”

Section: Discussionmentioning

confidence: 99%

Age-dependence of sensorimotor and cerebral electroencephalographic asymmetry in rats subjected to unilateral cerebrovascular stroke

Moyanova

Mitreva

Kortenska

et al. 2013

Exp & Trans Stroke Med

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BackgroundThe human population mostly affected by stroke is more than 65 years old. This study was designed to meet the recommendation that models of cerebral ischemia in aged animals are more relevant to the clinical setting than young animal models. Until now the majority of the pre-clinical studies examining age effects on stroke outcomes have used rats of old age. Considering the increasing incidence of stroke among younger than old human population, new translational approaches in animal models are needed to match the rejuvenation of stroke. A better knowledge of alterations in stroke outcomes in middle-aged rats has important preventive and management implications providing clues for future investigations on effects of various neuroprotective and neurorestorative drugs against cerebrovascular accidents that may occur before late senescence.MethodsWe evaluated the impact of transient focal ischemia, induced by intracerebral unilateral infusion of endothelin-1 (Et-1) near the middle cerebral artery of conscious rats, on volume of brain damage and asymmetry in behavioral and electroencephalographic (EEG) output measures in middle-aged (11–12 month-old) rats.ResultsWe did not find any age-dependent difference in the volume of ischemic brain damage three days after Et-1 infusion. However, age was an important determinant of neurological and EEG outcomes after stroke. Middle-aged ischemic rats had more impaired somatosensory functions of the contralateral part of the body than young ischemic rats and thus, had greater left-right reflex/sensorimotor asymmetry. Interhemispheric EEG asymmetry was more evident in middle-aged than in young ischemic rats, and this could tentatively explain the behavioral asymmetry.ConclusionsWith a multiparametric approach, we have validated the endothelin model of ischemia in middle-aged rats. The results provide clues for future studies on mechanisms underlying plasticity after brain damage and motivate investigations of novel neuroprotective strategies against cerebrovascular accidents that may occur before late senescence.

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“…The loss of neurons has been demonstrated directly by stereological cell counting and has been confirmed by DNA fragmentation assays and electron microscopy. The cell death is specific for neurons, and the neurons that die early are the thalamocortically projecting dLGN neurons, as determined by prelabeling neurons undergoing DNA fragmentation with retrograde tracer (Al-Abdulla et al, 1998; Al-Abdulla and Martin, 1998; Al-Abdulla and Martin, 2002), consistent with a target deprivation induced cell death. There is a delayed degeneration of dLGN interneurons (Al-Abdulla and Martin, 2002).…”

Section: Discussionmentioning

confidence: 96%

“…The cell death is specific for neurons, and the neurons that die early are the thalamocortically projecting dLGN neurons, as determined by prelabeling neurons undergoing DNA fragmentation with retrograde tracer (Al-Abdulla et al, 1998; Al-Abdulla and Martin, 1998; Al-Abdulla and Martin, 2002), consistent with a target deprivation induced cell death. There is a delayed degeneration of dLGN interneurons (Al-Abdulla and Martin, 2002). dLGN neuron degeneration after cortical ablation is apoptosis as determined light microscopy and electron microscopy (Al-Abdulla et al, 1998; Al-Abdulla and Martin, 1998; Al-Abdulla and Martin, 2002).…”

Section: Discussionmentioning

confidence: 96%

“…There is a delayed degeneration of dLGN interneurons (Al-Abdulla and Martin, 2002). dLGN neuron degeneration after cortical ablation is apoptosis as determined light microscopy and electron microscopy (Al-Abdulla et al, 1998; Al-Abdulla and Martin, 1998; Al-Abdulla and Martin, 2002). Similarly, in adult rat and mouse, sciatic nerve avulsion reliably causes loss (~60%) of motor neurons in lumbar spinal cord by an unequivocal apoptotic process (Martin et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

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Enforced DNA repair enzymes rescue neurons from apoptosis induced by target deprivation and axotomy in mouse models of neurodegeneration

Martin

Wong

2017

Mechanisms of Ageing and Development

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It is unknown whether DNA damage accumulation is an upstream instigator or secondary effect of the cell death process in different populations of adult postmitotic neurons in the central nervous system. In two different mouse models of injury-induced neurodegeneration characterized by relatively synchronous accumulation of mitochondria, oxidative stress, and DNA damage prior to neuronal apoptosis, we enforced the expression of human 8-oxoguanine DNA glycosylase (hOGG1) and human apurinic-pyrimidinic endonuclease/Ref1 (hAPE) using recombinant adenoviruses (Ad). Thalamic lateral geniculate neurons and lumbar spinal cord motor neurons were transduced by Ad-hOGG1 and Ad-hAPE injections into the occipital cortex and skeletal muscle, respectively, prior to their target deprivation- and axotomy-induced retrograde apoptosis. Enforced expression of hOGG1 and hAPE in thalamus and spinal cord was confirmed by western blotting and immunohistochemistry. In injured populations of neurons in thalamus and spinal cord, a DNA damage response (DDR) was registered, as shown by localization of phospho-activated p53, Rad17, and replication protein A-32 immunoreactivities, and this DDR was attenuated more effectively by enforced hAPE expression than by hOGG1 expression. Enforced expression of hOGG1 and hAPE significantly protected thalamic neurons and motor neurons from retrograde apoptosis induced by target deprivation and axotomy. We conclude a DDR response is engaged pre-apoptotically in different types of injured mature CNS neurons and that DNA repair enzymes can regulate the survival of retrogradely dying neurons, suggesting that DNA damage and activation of DDR are upstream mechanisms for this form of adult neurodegeneration in vivo, thus identifying DNA repair as a therapeutic target for neuroprotection.

show abstract

Projection neurons and interneurons in the lateral geniculate nucleus undergo distinct forms of degeneration ranging from retrograde and transsynaptic apoptosis to transient atrophy after cortical ablation in rat

Cited by 25 publications

References 24 publications

Visual deficits in a mouse model of Batten disease are the result of optic nerve degeneration and loss of dorsal lateral geniculate thalamic neurons

Visual deficits in a mouse model of Batten disease are the result of optic nerve degeneration and loss of dorsal lateral geniculate thalamic neurons

Age-dependence of sensorimotor and cerebral electroencephalographic asymmetry in rats subjected to unilateral cerebrovascular stroke

Enforced DNA repair enzymes rescue neurons from apoptosis induced by target deprivation and axotomy in mouse models of neurodegeneration

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