Phosphoinositide signaling in human brain

Mary A. Pacheco, Richard S Jope

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

The phosphoinositide signal transduction system constitutes one of the primary means for intercellular communication in the central nervous system, but only recently has this system been studied in human brain. Although some investigations have studied phosphoinositide signaling in slices from biopsied human brain, due to the limited access to such material a greater number of studies have utilized membranes prepared from postmortem human brain. With membranes exposed to exogenous labeled phosphoinositides, activation of phospholipase C with calcium, with G-proteins stimulated by GTPγS or NaF, or with several receptor agonists, have demonstrated that all of the components of the phosphoinositide system are retained in human brain membranes and are responsive to appropriate stimuli. Investigators have begun to examine the effects of neurological (Alzheimer's disease, epilepsy, Parkinson's disease) and psychiatric (schizophrenia, major depression, bipolar affective disorder) diseases on the activity of the phosphoinositide system. Alzheimer's disease has been studied to the greatest extent and a severe deficit in phosphoinositide signaling has been identified in most studies. In addition, brain regionally selective deficits in G-protein function associated with phosphoinositide signaling have been reported in subjects with major depression or with bipolar affective disorder, and in the latter an ameliorative effect of the therapeutic drug lithium was identified. Although significant progress has been achieved in studying the phosphoinositide system in human brain, many issues remaining to be addressed are discussed in this review. With carefully controlled studies, it appears that much will be learned in the near future about the phosphoinositide signal transduction system in human brain and the effects of a variety of disorders on its function.

Original languageEnglish
Pages (from-to)255-273
Number of pages19
JournalProgress in Neurobiology
Volume50
Issue number2-3
DOIs
StatePublished - Oct 1 1996
Externally publishedYes

Fingerprint

Phosphatidylinositols
Brain
Mood Disorders
Bipolar Disorder
GTP-Binding Proteins
Membranes
Signal Transduction
Alzheimer Disease
Depression
Phosphoinositide Phospholipase C
Therapeutic Uses
Lithium
Parkinson Disease
Psychiatry
Epilepsy
Schizophrenia
Central Nervous System
Research Personnel
Calcium
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Phosphoinositide signaling in human brain. / Pacheco, Mary A.; Jope, Richard S.

In: Progress in Neurobiology, Vol. 50, No. 2-3, 01.10.1996, p. 255-273.

Research output: Contribution to journalArticle

Pacheco, Mary A. ; Jope, Richard S. / Phosphoinositide signaling in human brain. In: Progress in Neurobiology. 1996 ; Vol. 50, No. 2-3. pp. 255-273.
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