Monitoring drug-induced neurodegeneration by imaging of peripheral benzodiazepine receptors.
Several drugs of abuse are known to produce an array of deleterious effects, including alterations in neuronal circuitry and, ultimately, neuronal degeneration. For instance, methamphetamine was shown to induce substantial nigrostriatal dopaminergic terminal damage, including an increase in glial fibrillary acidic protein, a marker for astrocyte proliferation. Nevertheless, there was almost no attempt to define neurodegeneration by measuring the abundance of reactive microglia. In fact, some investigators fail to differentiate between astrocytes and microglia and claim glial fibrillary acidic protein to be a marker for gliosis. To date, there are numerous methods designed to assess brain neuropathologies resulting from a wide arsenal of insults. Regardless of the cause of neuronal damage, reactive glial cells always appear at and around the site of degeneration. These cells are distinguished by the exceptional abundance of peripheral benzodiazepine receptors (PBRs; omicron3 sites), particularly as compared to surrounding neurons. Measuring the binding of specific ligands to these PBRs (for example, [3H]PK 11195) offers a unique indirect marker for reliable impairment estimation in the central nervous system. Moreover, the availability of agents such as [11C]PK 11195 paved the road to in vivo animal and human brain positron emission tomography scanning, demonstrating inflammation-like processes in several diseases. Additionally, the measurement of increased binding of PBR ligands provides a faithful indicator for the behavioral and cognitive deficits accompanying neuronal injury.
Weissman
Ben Avi
BA
Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, Israel. baw@iibr.gov.il
Brandeis
Rachel
R
Gilat
Eran
E
Cohen
Giora
G
Alkalay
David
D
Rabinovitz
Ishai
I
Sonego
Hagar
H
Raveh
Lily
L
D000818:Animals; D001570:Benzodiazepinones / Q000378:metabolism / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D013287:Illicit Drugs / Q000378:metabolism / Q000494:pharmacology; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D011963:Receptors, GABA-A / Q000378:metabolism*
D001570:Benzodiazepinones; D013287:Illicit Drugs; D011963:Receptors, GABA-A; C028513:4'-chlorodiazepam