Boglárka Makkai

Publications (3)10.12 Total impact

• Article: A comparative autoradiography study in post mortem whole hemisphere human brain slices taken from Alzheimer patients and age-matched controls using two radiolabelled DAA1106 analogues with high affinity to the peripheral benzodiazepine receptor (PBR) system.

  Balázs Gulyás, Boglárka Makkai, Péter Kása, Károly Gulya, Lidia Bakota, Szilvia Várszegi, Zsuzsa Beliczai, Jan Andersson, László Csiba, Andrea Thiele, Thomas Dyrks, Tetsua Suhara, Kazutoshi Suzuki, Makato Higuchi, Christer Halldin
  [show abstract] [hide abstract]
  ABSTRACT: The binding of two radiolabelled analogues (N-(5-[125I]Iodo-2-phenoxyphenyl)-N-(2,5-dimethoxybenzyl)acetamide ([125I]desfluoro-DAA1106) and N-(5-[125I]Fluoro-2-phenoxyphenyl)-N-(2-[125I]Iodo-5-methoxybenzyl)acetamide ([125I]desmethoxy-DAA1106) of the peripheral benzodiazepine receptor (PBR) (or TSPO, 18kDa translocator protein) ligand DAA1106 was examined by in vitro autoradiography on human post mortem whole hemisphere brain slices obtained from Alzheimer's disease (AD) patients and age-matched controls. Both [(125)I]desfluoro-IDAA1106 and [(125)I]desmethoxy-IDAA1106 were effectively binding to various brain structures. The binding could be blocked by the unlabelled ligand as well as by other PBR specific ligands. With both radiolabelled compounds, the binding showed regional inhomogeneity and the specific binding values proved to be the highest in the hippocampus, temporal and parietal cortex, the basal ganglia and thalamus in the AD brains. Compared with age-matched control brains, specific binding in several brain structures (temporal and parietal lobes, thalamus and white matter) in Alzheimer brains was significantly higher, indicating that the radioligands can effectively label-activated microglia and the up-regulated PBR/TSPO system in AD. Complementary immunohistochemical studies demonstrated reactive microglia activation in the AD brain tissue and indicated that increased ligand binding coincides with increased regional microglia activation due to neuroinflammation. These investigations yield further support to the PBR/TSPO binding capacity of DAA1106 in human brain tissue, demonstrate the effective usefulness of its radio-iodinated analogues as imaging biomarkers in post mortem human studies, and indicate that its radiolabelled analogues, labelled with short half-time bioisotopes, can serve as prospective in vivo imaging biomarkers of activated microglia and the up-regulated PBR/TSPO system in the human brain.
  Neurochemistry International 11/2008; 54(1):28-36. · 2.86 Impact Factor
• Article: Autoradiographic mapping of dopamine-D2/D3 receptor stimulated [35S]GTPgammaS binding in the human brain.

  Judit Sóvágó, Boglárka Makkai, Balázs Gulyás, Håkan Hall
  [show abstract] [hide abstract]
  ABSTRACT: Agonist stimulated [35S]guanosine 5'-gamma-thiotriphosphate ([35S]GTPgammaS) binding autoradiography was established for the examination of dopamine-D2/D2 receptors in human brain sections. The distribution of G proteins activated by dopamine-D2/D3 receptors was studied in whole hemisphere cryosections. Dopamine stimulated [35S]GTPgammaS binding in brain regions with high densities of dopamine D2-like receptors, i.e. putamen (23 +/- 2%, mean +/- SEM,% stimulation over basal binding), caudate (20 +/- 0%) and substantia nigra (22 +/- 2%), but also in regions with lower receptor densities such as amygdala (17 +/- 8%), hippocampus (16 +/- 6%), anterior cingulate (13 +/- 3%), and thalamus (12 +/- 2%). Dopamine stimulated [35S]GTPgammaS binding to significantly higher levels in the dorsal than in the ventral part of the striatum. Dopamine caused low or very low stimulation in all cortical areas. Raclopride, a selective D2/D3 receptor antagonist, potently inhibited dopamine stimulated [35S]GTPgammaS binding, whereas R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390), a selective D1 antagonist, did not block the [35S]GTPgammaS binding response stimulated by dopamine. Hence, the stimulatory effect of dopamine was primarily mediated by D2/D3 receptors. Quinpirole stimulated [35S]GTPgammaS binding in the same regions as dopamine. The maximal level of stimulation induced by dopamine and quinpirole was not significantly different. The present study demonstrates that agonist stimulated [35S]GTPgammaS binding autoradiography could be a suitable technique for the examination of dopamine-D2/D3 receptors in the human brain. This functional assay could provide useful new information about dopamine receptor/G protein coupling in the postmortem human brain, and reveal possible disease related alterations of the interaction between D2/D3 receptors and G proteins.
  European Journal of Neuroscience 08/2005; 22(1):65-71. · 3.63 Impact Factor
• Source

  Available from: balazs-gulyas.hu

  Article: Autoradiographic mapping of dopamine‐D2/D3 receptor stimulated [35S]GTPγS binding in the human brain

  Judit Sóvágó, Boglárka Makkai, Balázs Gulyás, Håkan Hall
  [show abstract] [hide abstract]
  ABSTRACT: Agonist stimulated [35S]guanosine 5′-γ-thiotriphosphate ([35S]GTPγS) binding autoradiography was established for the examination of dopamine-D2/D3 receptors in human brain sections. The distribution of G proteins activated by dopamine-D2/D3 receptors was studied in whole hemisphere cryosections. Dopamine stimulated [35S]GTPγS binding in brain regions with high densities of dopamine D2-like receptors, i.e. putamen (23 ± 2%, mean ± SEM,% stimulation over basal binding), caudate (20 ± 0%) and substantia nigra (22 ± 2%), but also in regions with lower receptor densities such as amygdala (17 ± 8%), hippocampus (16 ± 6%), anterior cingulate (13 ± 3%), and thalamus (12 ± 2%). Dopamine stimulated [35S]GTPγS binding to significantly higher levels in the dorsal than in the ventral part of the striatum. Dopamine caused low or very low stimulation in all cortical areas. Raclopride, a selective D2/D3 receptor antagonist, potently inhibited dopamine stimulated [35S]GTPγS binding, whereas R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390), a selective D1 antagonist, did not block the [35S]GTPγS binding response stimulated by dopamine. Hence, the stimulatory effect of dopamine was primarily mediated by D2/D3 receptors. Quinpirole stimulated [35S]GTPγS binding in the same regions as dopamine. The maximal level of stimulation induced by dopamine and quinpirole was not significantly different. The present study demonstrates that agonist stimulated [35S]GTPγS binding autoradiography could be a suitable technique for the examination of dopamine-D2/D3 receptors in the human brain. This functional assay could provide useful new information about dopamine receptor/G protein coupling in the postmortem human brain, and reveal possible disease related alterations of the interaction between D2/D3 receptors and G proteins.
  European Journal of Neuroscience 06/2005; 22(1):65 - 71. · 3.63 Impact Factor