Increased calbindin-D28k immunoreactivity in striatal projection neurons of R6/2 Huntington's disease transgenic mice

Sun, Zhiqiang; Wang, H. B.; Deng, Yunping; Lei, Wanlong; Xie, Jiangang; Meade, Christopher A.; Mar, Nobel Del; Goldowitz, Dan; Reiner, Anton

doi:10.1016/j.nbd.2005.05.023

Cited by 10 publications

(7 citation statements)

References 86 publications

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“…Early physiological changes in MSNs observed in animal models of HD are reminiscent of those observed in dopamine-depleted animals, including an increase in input resistance and a decrease in spine density (Klapstein et al, 2001), as well as increased expression of calcium binding proteins (Huang et al, 1995; Sun et al, 2005). While these changes may arise as a direct consequence of mutant htt expression in MSNs, another possibility is that they represent compensatory responses to increased excitatory drive from cortex.…”

Section: Basal Ganglia Circuit Function and Dysfunctionmentioning

confidence: 99%

Striatal Plasticity and Basal Ganglia Circuit Function

Kreitzer

Malenka

2008

Neuron

864

776

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The dorsal striatum, which consists of the caudate and putamen, is the gateway to the basal ganglia. It receives convergent excitatory afferents from cortex and thalamus and forms the origin of the direct and indirect pathways—distinct basal ganglia circuits involved in motor control. It is also a major site of activity-dependent synaptic plasticity. Striatal plasticity alters the transfer of information throughout basal ganglia circuits and may represent a key neural substrate for adaptive motor control and procedural memory. Here, we review current understanding of synaptic plasticity in the striatum and its role in the physiology and pathophysiology of basal ganglia function.

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Section: Basal Ganglia Circuit Function and Dysfunctionmentioning

confidence: 99%

Striatal Plasticity and Basal Ganglia Circuit Function

Kreitzer

Malenka

2008

Neuron

864

776

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“…The consequences of CalDAG-GEFII dysregulation in HD models still need to be evaluated. Interestingly, in contrast to CalDAG-GEFI, another matrix-enriched calcium-binding protein, calbindin-D28K, is up-regulated in HD and HD animal models, and this change has been suggested to be protective against calcium-induced excitotoxicity (Huang et al, 1995; Sun et al, 2005). Most striatum-enriched genes are down-regulated in HD however (Desplats et al, 2006), which may be a compensatory response to the differential vulnerability of the MSN cell-type to mutant Htt expression.…”

Section: Striosomes Signaling and Diseasementioning

confidence: 99%

Basal Ganglia Disorders Associated with Imbalances in the Striatal Striosome and Matrix Compartments

Crittenden¹,

Graybiel²

2011

Front. Neuroanat.

383

470

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The striatum is composed principally of GABAergic, medium spiny striatal projection neurons (MSNs) that can be categorized based on their gene expression, electrophysiological profiles, and input–output circuits. Major subdivisions of MSN populations include (1) those in ventromedial and dorsolateral striatal regions, (2) those giving rise to the direct and indirect pathways, and (3) those that lie in the striosome and matrix compartments. The first two classificatory schemes have enabled advances in understanding of how basal ganglia circuits contribute to disease. However, despite the large number of molecules that are differentially expressed in the striosomes or the extra-striosomal matrix, and the evidence that these compartments have different input–output connections, our understanding of how this compartmentalization contributes to striatal function is still not clear. A broad view is that the matrix contains the direct and indirect pathway MSNs that form parts of sensorimotor and associative circuits, whereas striosomes contain MSNs that receive input from parts of limbic cortex and project directly or indirectly to the dopamine-containing neurons of the substantia nigra, pars compacta. Striosomes are widely distributed within the striatum and are thought to exert global, as well as local, influences on striatal processing by exchanging information with the surrounding matrix, including through interneurons that send processes into both compartments. It has been suggested that striosomes exert and maintain limbic control over behaviors driven by surrounding sensorimotor and associative parts of the striatal matrix. Consistent with this possibility, imbalances between striosome and matrix functions have been reported in relation to neurological disorders, including Huntington’s disease, L-DOPA-induced dyskinesias, dystonia, and drug addiction. Here, we consider how signaling imbalances between the striosomes and matrix might relate to symptomatology in these disorders.

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“…Moreover, in HD, increased expression of the calcium-binding proteins parvalbumin and calretinin is positively associated with interneuron survival [206]. Parvalbumin and calretinin exert calcium-buffering effects in response to excessive calcium-induced excitotoxicity and are thought to be neuroprotective and important for the survival of interneurons [207,208]. However, the enrichment of calcium-permeable AMPA receptors in parvalbumin interneurons may be a potential pathogenic mechanism [209].…”

Section: Striatal Pathologymentioning

confidence: 99%

“…In HD, increased expression of calcium-binding protein calbindin-D28K is positively associated with interneuron survival [206]. Calbindin-D28K is predominantly found in the matrix and thought to exert neuroprotective effects that promote calcium-buffering in response to excessive calcium-induced excitotoxicity [207,208]. Crittenden et al found that calcium diacylglycerol guanine nucleotide exchange factors (CalDAG-GEFs), which are striatum-enriched calcium and diacylglycerol binding proteins, are severely down-regulated in the R6/2 mouse model of HD and post-mortem striatal tissues from patients with HD [89].…”

Section: Striatal Pathologymentioning

confidence: 99%

Striatal Vulnerability in Huntington’s Disease: Neuroprotection Versus Neurotoxicity

Morigaki

Goto

2017

Brain Sciences

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Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease caused by the expansion of a CAG trinucleotide repeat encoding an abnormally long polyglutamine tract (PolyQ) in the huntingtin (Htt) protein. In HD, striking neuropathological changes occur in the striatum, including loss of medium spiny neurons and parvalbumin-expressing interneurons accompanied by neurodegeneration of the striosome and matrix compartments, leading to progressive impairment of reasoning, walking and speaking abilities. The precise cause of striatal pathology in HD is still unknown; however, accumulating clinical and experimental evidence suggests multiple plausible pathophysiological mechanisms underlying striatal neurodegeneration in HD. Here, we review and discuss the characteristic neurodegenerative patterns observed in the striatum of HD patients and consider the role of various huntingtin-related and striatum-enriched proteins in neurotoxicity and neuroprotection.

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Increased calbindin-D28k immunoreactivity in striatal projection neurons of R6/2 Huntington's disease transgenic mice

Cited by 10 publications

References 86 publications

Striatal Plasticity and Basal Ganglia Circuit Function

Striatal Plasticity and Basal Ganglia Circuit Function

Basal Ganglia Disorders Associated with Imbalances in the Striatal Striosome and Matrix Compartments

Striatal Vulnerability in Huntington’s Disease: Neuroprotection Versus Neurotoxicity

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