Loss Of Projection Neurons Research Articles

Neuroanatomical and cellular degeneration associated with a social disorder characterized by new ritualistic belief systems in a TDP-C patient vs. a Pick patient.

Frontotemporal dementia (FTD) is a spectrum of clinically and pathologically heterogenous neurodegenerative dementias. Clinical and anatomical variants of FTD have been described and associated with underlying frontotemporal lobar degeneration (FTLD) pathology, including tauopathies (FTLD-tau) or TDP-43 proteinopathies (FTLD-TDP). FTD patients with predominant degeneration of anterior temporal cortices often develop a language disorder of semantic knowledge loss and/or a social disorder often characterized by compulsive rituals and belief systems corresponding to predominant left or right hemisphere involvement, respectively. The neural substrates of these complex social disorders remain unclear. Here, we present a comparative imaging and postmortem study of two patients, one with FTLD-TDP (subtype C) and one with FTLD-tau (subtype Pick disease), who both developed new rigid belief systems. The FTLD-TDP patient developed a complex set of values centered on positivity and associated with specific physical and behavioral features of pigs, while the FTLD-tau patient developed compulsive, goal-directed behaviors related to general themes of positivity and spirituality. Neuroimaging showed left-predominant temporal atrophy in the FTLD-TDP patient and right-predominant frontotemporal atrophy in the FTLD-tau patient. Consistent with antemortem cortical atrophy, histopathologic examinations revealed severe loss of neurons and myelin predominantly in the anterior temporal lobes of both patients, but the FTLD-tau patient showed more bilateral, dorsolateral involvement featuring greater pathology and loss of projection neurons and deep white matter. These findings highlight that the regions within and connected to anterior temporal lobes may have differential vulnerability to distinct FTLD proteinopathies and serve important roles in human belief systems.

Melatonin Ameliorates Injury and Specific Responses of Ischemic Striatal Neurons in Rats

Studies have confirmed that middle cerebral artery occlusion (MCAO) causes striatal injury in which oxidative stress is involved in the pathological mechanism. Increasing evidence suggests that melatonin may have a neuroprotective effect on cerebral ischemic damage. This study aimed to examine the morphological changes of different striatal neuron types and the effect of melatonin on striatal injury by MCAO. The results showed that MCAO induced striatum-related dysfunctions of locomotion, coordination, and cognition, which were remarkably relieved with melatonin treatment. MCAO induced severe striatal neuronal apoptosis and loss, which was significantly decreased with melatonin treatment. Within the outer zone of the infarct, the number of Darpp-32+ projection neurons and the densities of dopamine-receptor-1 (D1)+ and dopamine-receptor-2 (D2)+ fibers were reduced; however, both parvalbumin (Parv)+ and choline acetyltransferase (ChAT)+ interneurons were not significantly decreased in number, and neuropeptide Y (NPY)+ and calretinin (Cr)+ interneurons were even increased. With melatonin treatment, the loss of projection neurons and characteristic responses of interneurons were notably attenuated. The present study demonstrates that the projection neurons are rather vulnerable to ischemic damage, whereas the interneurons display resistance and even hyperplasia against injury. In addition, melatonin alleviates striatal dysfunction, neuronal loss, and morphological transformation of interneurons resulting from cerebral ischemia.

Neural grafts in Huntington's disease: viability after 10 years

One of the major pathological features of Huntington's disease is the loss of projection neurons in the striatum, a subcortical structure on which cortical fibres converge and then relay mostly to the globus pallidus and the substantia nigra. Diagnosis depends on the presence of the dominant mutant Huntingtin gene (HTT), and clinical features include motor, intellectual, and psychiatric disorders. Although pharmacological drugs can alleviate symptoms, there is no effective cure and the disease progresses to dementia, a bedridden state, and death in about 15–20 years after onset. Despite this distressing outlook, results from animal studies have shown that anatomical and functional integration of fetal cell transplants in the host brain can sustain cognitive and motor recovery (see elsewhere for reviews 1 Peschanski M Cesaro P Hantraye P Rationale for intrastriatal grafting of striatal neuroblasts in patients with Huntington's disease. Neuroscience. 1995; 68: 273-285 Crossref PubMed Scopus (130) Google Scholar , 2 Rosser AE Dunnett SB Cell transplantation for Huntington's disease should we continue?. Br Res Bull. 2007; 72: 132-147 Crossref PubMed Scopus (34) Google Scholar ).

Behavioral and anatomical effects of quinolinic acid in the striatum of the hemiparkinsonian rat

Parkinson's disease (PD), a hypokinetic disorder, and Huntington's disease (HD), a hyperkinetic disorder, share the fact that in the motor pathways the dysfunction starts in the striatum. In PD the projection neurons are overactive due to decreased inhibitory regulation by lost dopamine afferents, while in HD the output from the striatum is insufficient due to loss of projection neurons. This study aimed to determine whether the introduction of a mild HD condition in the PD striatum can counter the hypokinetic condition. The experiment was carried out in the 6-OHDA rat model for PD in which amphetamine, 5 mg/kg, evokes an asymmetric rotation response toward the side of the 6-OHDA lesion (ipsilateral rotation). The response to amphetamine in this study was fractionated into multiple components and measured automatically. After baseline measurements, the subjects were divided into four groups. Group I was unilaterally sham-lesioned in medial, central, and lateral striatum. Group II was injected quinolinic acid (QA) 20 nM in medial, central, and lateral striatum. Group III was injected QA 60 nM in central striatum. Group IV was injected QA 120 nM in central striatum. The effects of QA were measured weekly. The sham lesions in Group I had no effects. In Group II, ipsilateral rotation was reduced and replaced by oral stereotypy, a competitive behavior. In Group III, ipsilateral rotation decreased, but to a lesser degree than in Group II. In Group IV, QA had no effects. Histological findings show a unilateral loss of tyrosine immunoreactive (TH) neurons in substantia nigra and of fibers in striatum in all subjects. In addition, in Group II the striatum was atrophied. These findings suggest that the shift in Group II from ipsilateral rotation to oral stereotypy after QA was due to reduced striatal output caused by a loss of projection neurons, a loss insufficient to induce HD symptoms, but sufficient to counter the PD condition.

Reorganization of a telencephalic motor region during sexual differentiation and vocal learning in zebra finches

Male zebra finches learn to produce a vocal pattern during a sensitive period of development, whereas females do not. The motor output of telencephalic song processing is RA (the robust nucleus of the archistriatum), a region containing a population of projection neurons that descend to the hindbrain (nXIIts, the tracheo-syringeal portion of the hypoglossal nerve nucleus). In turn, nXIIts neurons innervate the vocal organ (syrinx). Previous work shows that the number of RA neurons is monomorphic in fledgling males and females. RA neuron number in males does not change thereafter, but females show a substantial developmental loss of RA neurons. Because the developmental sex difference in RA neuron number implies a change in the number of projection neurons within RA, we have made injections of retrograde tracer into the hindbrain to measure the percentage of RA neurons that project to nXIIts as a function of age in females and vocal development in males. In juveniles of both sexes, we found that close to two-thirds of RA neurons project to nXIIts. However, the percentage of RA neurons projecting to nXIIts declined by 44% during female development, and by 14% during a specific stage of male vocal development (the transition from subsong to plastic song). These data indicate that in addition to regulation of RA neuron number, sexual differentiation and vocal learning correlate with a significant decrease in the amount of descending input to the vocal organ. The loss of projection neurons during vocal learning is surprising in light of the stability of RA neuron number in males, and our findings suggest that the behavioral transition from subsong to plastic song may involve a restricted period of RA neuron loss and replacement and/or axon rearrangement.

Effects of suicide transport lesions of the striatopallidal or striatonigral pathways on striatal ultrastructure

In the basal ganglia, centrally active suicide transport agents produce selective lesions of the striatopallidal and striatonigral pathways based on receptor binding and neuropeptide mRNA studies. Anatomical analyses indicate a selective, albeit modest. loss of projection neurons. In the present study, we sought to determine the ultrastructural sequelae in the striatum of suicide transport injections of the globus pallidus (GP) or substantia nigra (SN). Neostriata of adult rats were examined 10 days after lesions of the striatopallidal or striatonigral pathways with OX7-saporin or volkensin. Controls consisted of normal unoperated rats and animals injected into either target with ricin, a toxic lectin that is not transported in the central nervous system. Injections with OX7-saporin or volkensin into the GP or SN produced a decrease in striatal synaptic density of approximately 20%, relative to the contralateral side. Dark degenerating profiles, though very rare in the contralateral striata, were present throughout the neuropil in the ipsilateral striata. In animals with striatopallidal lesions, axospinous synapses of both the asymmetric and symmetric type were decreased in density, while the number of synapses formed with dendritic shafts was unaffected. In addition, the number of striatal mitochondria) profiles was decreased ipsilateral to the lesions. In animals with striatonigral lesions, the number of axospinous and axodendritic synapses of the asymmetric type was decreased ipsilateral to the lesions. Synaptic density and ultrastructural integrity remained unaffected in the striata of animals receiving ricin injections and in the contralateral striata of animals receiving OX7-saporin or volkensin injections. Our results, taken together with previous studies showing marked loss of receptors, uptake sites and mRNA, suggest that while most synapses are present and intact. the efficacy of synaptic transmission may be altered.