Peripheral-type benzodiazepine receptors in diagnostic subtypes of schizophrenic patients

Wodarz, Norbert; Rothenhöfer, C; Fischer, Roswitha; Stöber, Gerald; Kiehl, Benno; Jungkunz, G.; Riederer, Peter; Klein, Helmfried E.

doi:10.1016/s0165-1781(98)00098-5

Cited by 11 publications

(6 citation statements)

References 32 publications

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“…Additionally, co-morbidity factors such as alcohol and substance abuse also influenced TSPO binding parameters. For example, using granulocytes, Wodarz et al, [1998] found a 38% decrease in [ 3 H]PK11195 Bmax in residual-type schizophrenics relative to controls. Similarly, Ritsner et al, [2003] found a 30% decrease in platelet [ 3 H]PK11195 Bmax in aggressive schizophrenia relative to controls.…”

Section: Tspo Studies In Schizophrenia Prior To Pet Imaging-a Historimentioning

confidence: 99%

TSPO in diverse CNS pathologies and psychiatric disease: A critical review and a way forward

Guilarte

2019

Pharmacology & Therapeutics

131

127

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The use of Translocator Protein 18 kDa (TSPO) as a clinical neuroimaging biomarker of brain injury and neuroinflammation has increased exponentially in the last decade. There has been a furious pace in the development of new radiotracers for TSPO positron emission tomography (PET) imaging and its use has now been extensively described in many neurological and mental disorders. This fast pace of research and the ever-increasing number of new laboratories entering the field often times lack an appreciation of the historical perspective of the field and introduce dogmatic, but unproven facts, related to the underlying neurobiology of the TSPO response to brain injury and neuroinflammation. Paradoxically, while in neurodegenerative disorders and in all types of CNS pathologies brain TSPO levels increase, a new observation in psychiatric disorders such as schizophrenia is decreased brain levels of TSPO measured by PET. The neurobiological bases for this new finding is currently not known, but rigorous experimental design using multiple experimental approaches and careful interpretation of results is critically important to provide the methodological and/or biological underpinnings to this new observation. This review provides a perspective of the early history of validating TSPO as a biomarker of brain injury and neuroinflammation and a critical analysis of controversial topics in the literature related to the cellular sources of the TSPO response. The latter is important in order to provide the correct interpretation of PET studies in neurodegenerative and psychiatric disorders. Furthermore, this review proposes some yet to be explored explanations to new findings in psychiatric disorders and new approaches to quantitatively assess the glial sources of the TSPO response in order to move the field forward.

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Section: Tspo Studies In Schizophrenia Prior To Pet Imaging-a Historimentioning

confidence: 99%

TSPO in diverse CNS pathologies and psychiatric disease: A critical review and a way forward

Guilarte

2019

Pharmacology & Therapeutics

131

127

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“…Differences in ligand binding parameters (e.g., B max , K d ) to granulocytic PBRs have been observed in schizophrenic patients, with reduced B max values found for residual subtype schizophrenic patients compared to controls [Wodarz et al, 1998]. The residual subtype patients also had lower B max values than schizophrenic patients with predominantly positive symptoms (ibid).…”

Section: Dbi/pbr and Behaviormentioning

confidence: 99%

Multiple missense mutations in the diazepam binding inhibitor (DBI) gene identified in schizophrenia but lack of disease association

Niu

Rice

Heston

et al. 2003

American J of Med Genetics Pt B

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The diazepam binding inhibitor (DBI), alternatively known as the acyl-CoA binding protein (ACBP), is involved in multiple biological actions. The polypeptide binds to the peripheral, or mitochondrial, benzodiazepine receptor and facilitates transport of cholesterol to the inner membrane to stimulate steroid synthesis. Through this action, DBI indirectly modulates gamma-aminobutyric acid (GABA)-mediated inhibitory neurotransmission. DBI can be postulated as a candidate gene for psychiatric phenotypes including anxiety, mood, and psychotic disorders. In an examination of the DBI gene among 112 individuals with schizophrenia, our laboratory has identified 18 novel single nucleotide polymorphisms (SNPs), including three missense changes in conserved amino acids, a coding region microdeletion, and multiple SNPs in the putative promoter region. Case-control association analyses were performed for the missense changes, but none was found to be significantly associated with disease.

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“…TSPO has been shown to be down-regulated in a range of psychological conditions [ 20 ]. TSPO is down-regulated in anxiety disorders, such as generalised anxiety [ 21 ] and social anxiety disorder [ 22 ] posttraumatic stress disorder [ 23 ], and schizophrenia [ 24 ]. A polymorphism in the TSPO gene, 485G>A, results in higher susceptibility of the patients to panic disorder [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Expression and purification of the mammalian translocator protein for structural studies

Graeber

Korkhov

2018

PLoS ONE

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The translocator protein (TSPO) is an 18 kDa polytopic membrane protein of the outer mitochondrial membrane, abundantly present in the steroid-synthesising cells. TSPO has been linked to a number of disorders, and it is recognised as a promising drug target with a range of potential medical applications. Structural and biochemical characterisation of a mammalian TSPO requires expression and purification of the protein of high quality in sufficiently large quantities. Here we describe detailed procedures for heterologous expression and purification of mammalian TSPO in HEK293 cells. We demonstrate that the established procedures can be used for untagged TSPO as well as for C-terminally fused TSPO constructs. Our protocol can be routinely used to generate high-quality TSPO preparations for biochemical and structural studies.

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Peripheral-type benzodiazepine receptors in diagnostic subtypes of schizophrenic patients

Cited by 11 publications

References 32 publications

TSPO in diverse CNS pathologies and psychiatric disease: A critical review and a way forward

TSPO in diverse CNS pathologies and psychiatric disease: A critical review and a way forward

Multiple missense mutations in the diazepam binding inhibitor (DBI) gene identified in schizophrenia but lack of disease association

Expression and purification of the mammalian translocator protein for structural studies

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