Calbindin D28K as a marker for the degeneration of the striatonigral pathway in Huntington's disease

Kiyama, Hiroshi; Seto‐Ohshima, Akiko; Emson, Piers C.

doi:10.1016/0006-8993(90)90866-a

Cited by 106 publications

(45 citation statements)

References 26 publications

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“…These CB ϩ neurons are larger and more intensely stained than the striatal projection neurons and are distributed in both the patch and the matrix compartments (Kiyama et al, 1990;Bennett and Bolam, 1993;Kubota and Kawaguchi, 1993). In our double-labeling experiments we found that a small number of CB ϩ neurons contained NKX2.1 (arrows in Fig.…”

Section: Nkx21 Is Expressed In Most Striatal Interneuronsmentioning

confidence: 51%

Origin and Molecular Specification of Striatal Interneurons

2000

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The striatum, the largest component of the basal ganglia, contains projection neurons and interneurons. Whereas there is considerable agreement that the lateral ganglionic eminence (LGE) is the origin of striatal projection neurons, less is known about the origin of striatal interneurons. Using focal injections of retrovirus into the ventral telencephalon in vitro, we demonstrate that most striatal interneurons tangentially migrate from the medial ganglionic eminence (MGE) or the adjacent preoptic/anterior entopeduncular areas (POa/AEP) and express the NKX2.1 homeodomain protein. Although the majority of striatal interneurons (cholinergic, calretinin ϩ , and parvalbumin ϩ ) maintain the expression of NKX2.1 into adulthood, most of the interneurons expressing somatostatin (SOM), neuropeptide Y (NPY), and neural nitric oxide synthase (NOS) appear to downregulate the expression of NKX2.1 as they exit the neuroepithelium. Analysis of striatal development in mice lacking Nkx2.1 suggests that this gene is required for the specification of nearly all striatal interneurons. Similar analysis of mice lacking the Mash1 basic helix-loop-helix (bHLH) or both the Dlx1 and Dlx2 homeodomain transcription factors demonstrates that these genes are required for the differentiation of striatal interneurons. Mash1 mutants primarily have a reduction in early-born striatal interneurons, whereas Dlx1/2 mutants primarily have reduced numbers of late-born striatal interneurons. We also present evidence implicating the Lhx6 and Lhx7 LIM-homeobox genes in the development of distinct interneuron subtypes. Finally, we hypothesize that, within the MGE, radially migrating cells generally become projection neurons, whereas tangentially migrating cells mainly form interneurons of the striatum and cerebral cortex.

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Section: Nkx21 Is Expressed In Most Striatal Interneuronsmentioning

confidence: 51%

Origin and Molecular Specification of Striatal Interneurons

2000

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“…Among the behavioral difficulties patients experience are issues involving executive function, emotionality, reasoning, and motor skills, all of which are mediated by the FC and/or CB functions [64,65]. A reduction in Calb1 gene and/or protein expression has been detected in brains of patients who suffered from an assortment of neurodegenerative diseases [66,67,68], and several neurobehavioral disorders are correlated with decreased size and/or numbers of Purkinje cells [69,70]. Sex differences in these brain regions in normal animals, such as those reported here, could provide clues underlying the etiologies of these diseases.…”

Section: Discussionmentioning

confidence: 99%

Sex Differences in the Cerebellum and Frontal Cortex: Roles of Estrogen Receptor Alpha and Sex Chromosome Genes

Abel¹,

Witt²,

Rissman³

2011

Neuroendocrinology

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Most neurobehavioral diseases are sexually dimorphic in their incidence, and sex differences in the brain may be key for understanding and treating these diseases. Calbindin (Calb) D28K is used as a biomarker for the well-studied sexually dimorphic nucleus, a hypothalamic structure that is larger in males than in females. In the current study weanling C56BL/6J mice were used to examine sex differences in the Calb protein and message focusing on regions outside of the hypothalamus. A robust sex difference was found in Calb in the frontal cortex (FC) and cerebellum (CB; specifically in Purkinje cells); mRNA and protein were higher in females than in males. Using 2 mouse lines, i.e. one with a complete deletion of estrogen receptor alpha (ERα) and the other with uncoupled gonads and sex chromosomes, we probed the mechanisms that underlie sexual dimorphisms. In the FC, deletion of ERα reduced Calb1 mRNA in females compared to males. In addition, females with XY sex chromosomes had levels of Calb1 equal to those of males. Thus, both ERα and the sex chromosome complement regulate Calb1 in the FC. In the CB, ERα knockout mice of both sexes had reduced Calb1 mRNA, yet sex differences were retained. However, the sex chromosome complement, regardless of gonadal sex, dictated Calb1 mRNA levels. Mice with XX chromosomes had significantly greater Calb1 than did XY mice. This is the first study demonstrating that sex chromosome genes are a driving force producing sex differences in the CB and FC, which are neuoranatomical regions involved in many normal functions and in neurobehavioral diseases.

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“…The polyclonal antibodies used were raised in guinea pigs against synthetic peptide sequences specific for the various subunits as follows: ␣ 2 subunit residues 1-9, ␣ 3 subunit residues 1-15, and ␥ 2 subunit residues 1-29 (Benke et al, 1991;Gao et al, 1993;Benke et al, 1994;Fritschy and Mohler, 1995). Other antibodies used were rabbit polyclonal antibodies against glutamic acid decarboxylase (GAD; K2 Chemicon, Temecula, CA), Calb (Emson, Cambridge, UK;Seto-Ohshima et al, 1988;Kiyama et al, 1990), Calr (SWant, Bellinzona, Switzerland), Parv (SWant), ChAT (SWant), NPY (Sigma, St Louis, MO), goat polyclonal antibody against ChAT (Chemicon) and monoclonal antibodies against Calb (SWant), Parv (Sigma), and Enk (Seralab Ltd., Crawley Down, U.K.). All antibodies were dissolved in immunobuffer consisting of 1% goat serum in PBS with 0.2% Triton-X and 0.4% Thimerosol (Sigma), except for goat anti-ChAT, which was dissolved in PBS with 0.2% Triton-X.…”

Section: Immunohistochemical Proceduresmentioning

confidence: 99%