IL-1β immunoreactive neurons in the human hypothalamus: reduced numbers in multiple sclerosis

Huitinga, Inge; Cammen, Maarten Van Der; Salm, Liesbeth P.; Erkut, Zeynel A.; Dam, Anne Marie Van; Tilders, F. J. H.; Swaab, Dick F.

doi:10.1016/s0165-5728(00)00248-4

Cited by 51 publications

(44 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Aberrant synthesis of IL-1␤ in the brain contributes to the development of acute and chronic CNS pathologies such as Alzheimer's disease, Down's syndrome, and multiple sclerosis (Griffin et al, 1989;Rothwell et al, 1997;Huitinga et al, 2000). Interestingly, increased expression of IL-1␤ and MMPs occurs simultaneously at sites of inflammation in which MMPs have been shown to control the biological activity of IL-1␤ (Ito et al, 1996;Schönbeck et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Genes Are Upregulated in Expanded Ataxin-3-Expressing Cell Lines and Spinocerebellar Ataxia Type 3 Brains

et al. 2001

View full text Add to dashboard Cite

Spinocerebellar ataxia type 3 (SCA3) is a polyglutamine disorder caused by a CAG repeat expansion in the coding region of a gene encoding ataxin-3. To study putative alterations of gene expression induced by expanded ataxin-3, we performed PCRbased cDNA subtractive hybridization in a cell culture model of SCA3. In rat mesencephalic CSM14.1 cells stably expressing expanded ataxin-3, we found a significant upregulation of mRNAs encoding the endopeptidase matrix metalloproteinase 2 (MMP-2), the transmembrane protein amyloid precursor protein, the interleukin-1 receptor-related Fos-inducible transcript, and the cytokine stromal cell-derived factor 1␣ (SDF1␣). Immunohistochemical studies of the corresponding or associated proteins in human SCA3 brain tissue confirmed these findings, showing increased expression of MMP-2 and amyloid ␤-protein (A␤) in pontine neurons containing nuclear inclusions. In addition, extracellular A␤-immunoreactive deposits were detected in human SCA3 pons. Furthermore, pontine neurons of SCA3 brains strongly expressed the antiinflammatory interleukin-1 receptor antagonist, the proinflammatory cytokine interleukin-1␤, and the proinflammatory chemokine SDF1. Finally, increased numbers of reactive astrocytes and activated microglial cells were found in SCA3 pons. These results suggest that inflammatory processes are involved in the pathogenesis of SCA3.

show abstract

Section: Discussionmentioning

confidence: 99%

Inflammatory Genes Are Upregulated in Expanded Ataxin-3-Expressing Cell Lines and Spinocerebellar Ataxia Type 3 Brains

et al. 2001

View full text Add to dashboard Cite

show abstract

“…70,71 CRF production is stimulated by proinflammatory cytokines such as IL1b, 72,73 produced by glial cells and PVN neurons. 30 Also TNFa, a circulating state marker for depression may stimulate CRF production. 31,74 In addition, TNFa is produced by astrocytes and ependymal cells.…”

Section: Cytokinesmentioning

confidence: 99%

“…MR and GR can form hetero-and homodimers that differ in their activity of gene regulation. A change in the balance of MR/GR ratio in depressed patients may contribute to the change in transcription rate of CRF [16][17][18][19][20] ; (2) the CRF receptors, that is, CRFR1 that stimulates CRF production 21,22 and CRFR2 that opposes this action 23 ; (3) alterations in vasopressinergic systems that potentiate effects of CRF 24 and the AVP receptor 1a (AVPR1A) that is involved in anxiety/ depressionrelated behavior 25 ; oxytocin (OXT) that attenuates the stress response was found to be increased in the PVN only in melancholic depression 26 ; (4) cAMP-response element-binding protein (CREB) that stimulates CRF expression as a transcription factor 27 ; (5) sex hormones, involving estrogen-receptors (ESR) 1 and 2 and androgen-receptor (AR), stimulating and inhibiting CRF gene expression, respectively 28,29 ; (6) the powerful CRF-stimulating proinflammatory cytokines such as interleukin 1-b (IL1b) that is produced by glial cells and PVN neurons, 30 and tumor necrosis factor-a (TNFa), a circulating state marker for depression 31 that is also produced by glial cells 32 ;…”

Section: Introductionmentioning

confidence: 99%

Gene expression analysis in the human hypothalamus in depression by laser microdissection and real-time PCR: the presence of multiple receptor imbalances

et al. 2008

View full text Add to dashboard Cite

Hyperactivity of corticotropin-releasing factor (CRF) neurons in the paraventricular nucleus (PVN) of the hypothalamus is a prominent feature in depression and may be important in the etiology of this disease. The activity of the CRF neurons in the stress response is modulated by a number of factors that stimulate or inhibit CRF expression, including (1) corticosteroid receptors and their chaperones, heat shock proteins 70 and 90, (2) sex hormone receptors, (3) CRF receptors 1 (CRFR1) and 2, (4) cytokines interleukin 1-b and tumor necrosis factor-a, (5) neuropeptides and receptors, vasopressin (AVP), AVP receptor 1a (AVPR1A) and oxytocin and (6) transcription factor cAMP-response element-binding protein. We hypothesized that, in depression, the transcript levels of those genes that are involved in the activation of the hypothalamo-pituitary-adrenal (HPA) axis are upregulated, whereas the transcript levels of the genes involved in the inhibition of the HPA axis are downregulated. We performed laser microdissection and real-time PCR in the PVN and as a control in the supraoptic nucleus. Snap-frozen post-mortem hypothalami of seven depressed and seven matched controls were used. We found significantly increased CRF mRNA levels in the PVN of the depressed patients. This was accompanied by a significantly increased expression of four genes that are involved in the activation of CRF neurons, that is, CRFR1, estrogen receptor-a, AVPR1A and mineralocorticoid receptor, while the expression of the androgen receptor mRNA involved in the inhibition of CRF neurons was decreased significantly. These findings raise the possibility that a disturbed balance in the production of receptors may contribute to the activation of the HPA axis in depression.

show abstract

“…For the immunocytochemical study of the colocalization of CRH and AR, the monoclonal rat anti-CRH 'PFU 83' (IgG2a subclass) antibody (kindly provided by Professor FJH Tilders), aimed at the C-terminal part (amino acid 38-39) of rat/human CRH, [41][42][43] and a polyclonal rabbit anti-AR antibody, ARIE, raised in our institute against the first 20 amino acids of human AR peptide sequence of the N-terminus, coupled to thyroglobulin by glutaraldehyde, were used. Specificity of the antibody rat IgG, PFU83 had been confirmed previously, 41,44 whereas the specificity of ARIE is described below.…”

Section: Immunocytochemical Studymentioning

confidence: 99%

A direct androgenic involvement in the expression of human corticotropin-releasing hormone

Fischer

et al. 2006

Mol Psychiatry

104

View full text Add to dashboard Cite

We investigated the possibility of a direct action of androgens on the expression of the human corticotropin-releasing hormone (CRH), which plays a central role in the hypothalamicpituitary-adrenal (HPA)-axis. Colocalization of CRH and nuclear/cytoplasmic androgen receptor (AR) was found in neurons of the paraventricular nucleus (PVN) in the human hypothalamus. A potential androgen-responsive element (ARE) in the human CRH promoter was subsequently analyzed with bandshifts and cotransfections in neuroblastoma cells. In the presence of testosterone, recombinant human AR bound specifically to the CRH-ARE. Expression of AR in combination with testosterone repressed CRH promoter activity through the ARE. We conclude that androgens may directly affect CRH neurons in the human PVN via AR binding to the CRH-ARE, which may have consequences for sex-specific pathogenesis of mood disorders.

show abstract

IL-1β immunoreactive neurons in the human hypothalamus: reduced numbers in multiple sclerosis

Cited by 51 publications

References 59 publications

Inflammatory Genes Are Upregulated in Expanded Ataxin-3-Expressing Cell Lines and Spinocerebellar Ataxia Type 3 Brains

Inflammatory Genes Are Upregulated in Expanded Ataxin-3-Expressing Cell Lines and Spinocerebellar Ataxia Type 3 Brains

Gene expression analysis in the human hypothalamus in depression by laser microdissection and real-time PCR: the presence of multiple receptor imbalances

A direct androgenic involvement in the expression of human corticotropin-releasing hormone

Contact Info

Product

Resources

About