Functional recovery of cholinergic basal forebrain neurons under disease conditions

Old problems, new solutions?

Wolfgang Härtig, Andreas Bauer, Kurt Brauer, Jens Grosche, T. Hortobágyi, B. Penke, Reinhard Schliebs, Tibor Harkany

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Recognition of the involvement of cholinergic neurons in the modulation of cognitive functions and their severe dysfunction in neurodegenerative disorders, such as Alzheimer's disease, initiated immense research efforts aimed at unveiling the anatomical organization and cellular characteristics of the basal forebrain (BFB) cholinergic system. Concomitant with our unfolding knowledge about the structural and functional complexity of the BFB cholinergic projection system, multiple pharmacological strategies were introduced to rescue cholinergic nerve cells from noxious attacks; however, a therapeutic breakthrough is still awaited. In this review, we collected recent findings that significantly contributed to our better understanding of cholinergic functions under disease conditions, and to the design of effective means to restore lost or damaged cholinergic functions. To this end, we first provide a brief survey of the neuroanatomical organization of BFB nuclei with emphasis on major evolutionary differences among mammalian species, in particular rodents and primates, and discuss limitations of the translation of experimental data to human therapeutic applications. Subsequently, we summarize the involvement of cholinergic dysfunction in the pathogenesis of severe neurological conditions, including stroke, traumatic brain injury, virus encephalitis and Alzheimer's disease, and emphasize the critical role of proinflammatory cytokines as common mediators of cholinergic neuronal damage. Moreover, we review leading functional concepts on the limited recovery of cholinergic neurons and their impaired plastic re-modeling, as well as on the hampered interplay of the ascending cholinergic and monoaminergic projection systems under neurodegenerative conditions. In addition, recent advances in the dynamic labeling of living cholinergic neurons by fluorochromated antibodies, referred to as in vivo labeling, and novel neuroimaging approaches as potential diagnostic tools of progressive cholinergic decline are surveyed. Finally, the potential of cell replacement strategies using embryonic and adult stem cells, and multipotent neural progenitors, as a means to recover damaged cholinergic functions, is discussed.

Original languageEnglish
Pages (from-to)95-165
Number of pages71
JournalReviews in the Neurosciences
Volume13
Issue number2
Publication statusPublished - 2002

Fingerprint

Cholinergic Agents
Neurons
Cholinergic Neurons
Alzheimer Disease
Basal Forebrain
Adult Stem Cells
Virus Diseases
Embryonic Stem Cells
Basal Ganglia
Neuroimaging
Neurodegenerative Diseases
Cognition
Primates
Plastics
Rodentia
Stroke
Pharmacology
Cytokines
Antibodies
Therapeutics

Keywords

  • Alzheimer's disease
  • Cell replacement
  • Excitotoxicity
  • In vivo labeling
  • Inflammation
  • Neuroimaging
  • Stem cell

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Functional recovery of cholinergic basal forebrain neurons under disease conditions : Old problems, new solutions? / Härtig, Wolfgang; Bauer, Andreas; Brauer, Kurt; Grosche, Jens; Hortobágyi, T.; Penke, B.; Schliebs, Reinhard; Harkany, Tibor.

In: Reviews in the Neurosciences, Vol. 13, No. 2, 2002, p. 95-165.

Research output: Contribution to journalArticle

Härtig, Wolfgang ; Bauer, Andreas ; Brauer, Kurt ; Grosche, Jens ; Hortobágyi, T. ; Penke, B. ; Schliebs, Reinhard ; Harkany, Tibor. / Functional recovery of cholinergic basal forebrain neurons under disease conditions : Old problems, new solutions?. In: Reviews in the Neurosciences. 2002 ; Vol. 13, No. 2. pp. 95-165.
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