Journal Article DZNE-2024-00850

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Neuropeptide FF (NPFF)-positive nerve cells of the human cerebral cortex and white matter in controls, selected neurodegenerative diseases, and schizophrenia.

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2024
Biomed Central London

Acta Neuropathologica Communications 12(1), 108 () [10.1186/s40478-024-01792-1]

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Abstract: We quantified and determined for the first time the distribution pattern of the neuropeptide NPFF in the human cerebral cortex and subjacent white matter. To do so, we studied n = 9 cases without neurological disorders and n = 22 cases with neurodegenerative diseases, including sporadic amyotrophic lateral sclerosis (ALS, n = 8), Alzheimer's disease (AD, n = 8), Pick's disease (PiD, n = 3), and schizophrenia (n = 3). NPFF-immunopositive cells were located chiefly, but not exclusively, in the superficial white matter and constituted there a subpopulation of white matter interstitial cells (WMIC): Pyramidal-like and multipolar somata predominated in the gyral crowns, whereas bipolar and ovoid somata predominated in the cortex surrounding the sulci. Their sparsely ramified axons were unmyelinated and exhibited NPFF-positive bead-like varicosities. We found significantly fewer NPFF-immunopositive cells in the gray matter of the frontal, cingulate, and superior temporal gyri of both sporadic ALS and late-stage AD patients than in controls, and significantly fewer NPFF-positive cells in the subjacent as well as deep white matter of the frontal gyrus of these patients compared to controls. Notably, the number of NPFF-positive cells was also significantly lower in the hippocampal formation in AD compared to controls. In PiD, NPFF-positive cells were present in significantly lower numbers in the gray and white matter of the cingulate and frontal gyrii in comparison to controls. In schizophrenic patients, lower wNPFF cell counts in the neocortex were significant and global (cingulate, frontal, superior temporal gyrus, medial, and inferior gyri). The precise functions of NPFF-positive cells and their relationship to the superficial corticocortical white matter U-fibers are currently unknown. Here, NPFF immunohistochemistry and expression characterize a previously unrecognized population of cells in the human brain, thereby providing a new entry-point for investigating their physiological and pathophysiological roles.

Keyword(s): Humans (MeSH) ; White Matter: pathology (MeSH) ; White Matter: metabolism (MeSH) ; Male (MeSH) ; Schizophrenia: pathology (MeSH) ; Schizophrenia: metabolism (MeSH) ; Female (MeSH) ; Cerebral Cortex: pathology (MeSH) ; Cerebral Cortex: metabolism (MeSH) ; Aged (MeSH) ; Middle Aged (MeSH) ; Neurodegenerative Diseases: pathology (MeSH) ; Neurodegenerative Diseases: metabolism (MeSH) ; Aged, 80 and over (MeSH) ; Oligopeptides (MeSH) ; Adult (MeSH) ; Neurons: pathology (MeSH) ; Neurons: metabolism (MeSH) ; Alzheimer’s disease ; Alzheimer’s disease ; Amyotrophic lateral sclerosis ; Cerebral cortex ; Human brain ; Interneurons ; NOS (type I) ; Neurodegeneration ; Neuropeptide FF (NPFF) ; Pick’s disease ; Schizophrenia ; Somatostatin ; U-fibers ; White matter interstitial cells ; phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide ; Oligopeptides ; Pick’s disease

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Contributing Institute(s):
  1. Metabolic Changes in Neurodegeneration (AG Roselli)
  2. Translational Protein Biochemistry (AG Böckers)
  3. Clinical Study Center Ulm (Clinical Study Center Ulm ; Clinical Study Center (Ulm))
Research Program(s):
  1. 352 - Disease Mechanisms (POF4-352) (POF4-352)
  2. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2024
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Institute Collections > UL DZNE > UL DZNE-Clinical Study Center (Ulm)
Document types > Articles > Journal Article
Institute Collections > UL DZNE > UL DZNE-AG Böckers
Institute Collections > UL DZNE > UL DZNE-AG Roselli
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 Record created 2024-07-16, last modified 2024-08-09