Nicotinic receptors mediate stress-nicotine detrimental interplay via dopamine cells’ activity

Epidemiological studies report strong association between mood disorders and tobacco addiction. This high comorbidity requires adequate treatment but the underlying mechanisms are unknown. We demonstrate that nicotine exposure, independent of drug withdrawal effects, increases stress sensitivity, a major risk factor in mood disorders. Nicotine and stress concur to induce long-lasting cellular adaptations within the dopamine (DA) system. This interplay is underpinned by marked remodeling of nicotinic systems, causing increased ventral tegmental area (VTA) DA neurons’ activity and stress-related behaviors, such as social aversion. Blocking β2 or α7 nicotinic acetylcholine receptors (nAChRs) prevents, respectively, the development and the expression of social stress-induced neuroadaptations; conversely, facilitating α7 nAChRs activation specifically in the VTA promotes stress-induced cellular and behavioral maladaptations. Our work unravels a complex nicotine-stress bidirectional interplay and identifies α7 nAChRs as a promising therapeutic target for stress-related psychiatric disorders

Intelligence, educational attainment, and brain structure in those at familial high-risk for schizophrenia or bipolar disorder

First-degree relatives of patients diagnosed with schizophrenia (SZ-FDRs) show similar patterns of brain abnormalities and cognitive alterations to patients, albeit with smaller effect sizes. First-degree relatives of patients diagnosed with bipolar disorder (BD-FDRs) show divergent patterns; on average, intracranial volume is larger compared to controls, and findings on cognitive alterations in BD-FDRs are inconsistent. Here, we performed a meta-analysis of global and regional brain measures (cortical and subcortical), current IQ, and educational attainment in 5,795 individuals (1,103 SZ-FDRs, 867 BD-FDRs, 2,190 controls, 942 schizophrenia patients, 693 bipolar patients) from 36 schizophrenia and/or bipolar disorder family cohorts, with standardized methods. Compared to controls, SZ-FDRs showed a pattern of widespread thinner cortex, while BD-FDRs had widespread larger cortical surface area. IQ was lower in SZ-FDRs (d = −0.42, p = 3 × 10−5), with weak evidence of IQ reductions among BD-FDRs (d = −0.23, p =.045). Both relative groups had similar educational attainment compared to controls. When adjusting for IQ or educational attainment, the group-effects on brain measures changed, albeit modestly. Changes were in the expected direction, with less pronounced brain abnormalities in SZ-FDRs and more pronounced effects in BD-FDRs. To conclude, SZ-FDRs and BD-FDRs show a differential pattern of structural brain abnormalities. In contrast, both had lower IQ scores and similar school achievements compared to controls. Given that brain differences between SZ-FDRs and BD-FDRs remain after adjusting for IQ or educational attainment, we suggest that differential brain developmental processes underlying predisposition for schizophrenia or bipolar disorder are likely independent of general cognitive impairment

The Sariçiçek howardite fall in Turkey: Source crater of HED meteorites on Vesta and impact risk of Vestoids

###EgeUn###The Sariçiçek howardite meteorite shower consisting of 343 documented stones occurred on September 2, 2015 in Turkey and is the first documented howardite fall. Cosmogenic isotopes show that Sariçiçek experienced a complex cosmic-ray exposure history, exposed during ~12–14 Ma in a regolith near the surface of a parent asteroid, and that an ~1 m sized meteoroid was launched by an impact 22 ± 2 Ma ago to Earth (as did one-third of all HED meteorites). SIMS dating of zircon and baddeleyite yielded 4550.4 ± 2.5 Ma and 4553 ± 8.8 Ma crystallization ages for the basaltic magma clasts. The apatite U-Pb age of 4525 ± 17 Ma, K-Ar age of ~3.9 Ga, and the U,Th-He ages of 1.8 ± 0.7 and 2.6 ± 0.3 Ga are interpreted to represent thermal metamorphic and impact-related resetting ages, respectively. Petrographic; geochemical; and O-, Cr-, and Ti-isotopic studies confirm that Sariçiçek belongs to the normal clan of HED meteorites. Petrographic observations and analysis of organic material indicate a small portion of carbonaceous chondrite material in the Sariçiçek regolith and organic contamination of the meteorite after a few days on soil. Video observations of the fall show an atmospheric entry at 17.3 ± 0.8 km s -1 from NW; fragmentations at 37, 33, 31, and 27 km altitude; and provide a pre-atmospheric orbit that is the first dynamical link between the normal HED meteorite clan and the inner Main Belt. Spectral data indicate the similarity of Sariçiçek with the Vesta asteroid family (V-class) spectra, a group of asteroids stretching to delivery resonances, which includes (4) Vesta. Dynamical modeling of meteoroid delivery to Earth shows that the complete disruption of a ~1 km sized Vesta family asteroid or a ~10 km sized impact crater on Vesta is required to provide sufficient meteoroids ?4 m in size to account for the influx of meteorites from this HED clan. The 16.7 km diameter Antionia impact crater on Vesta was formed on terrain of the same age as given by the 4 He retention age of Sariçiçek. Lunar scaling for crater production to crater counts of its ejecta blanket show it was formed ~22 Ma ago. © The Meteoritical Society, 2019.58261, 40339 nccr – on the move NNX14AM62G MFAG/113F035 Simons Foundation: 302497 NNX14-AR92G, NNX16AD34G Academy of Finland: 299543 Government Council on Grants, Russian Federation: ? 02., A03.21.0006 Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung: PZ00P2_154874 Ministry of Education and Science of the Russian Federation: 3.1959.2017/4.6 National Natural Science Foundation of China: 41403055Acknowledgments—We thank N. Ergu€n and family in the village of Sari©ci©cek for donating the meteorites studied here and collecting meteorite fall coordinates. We thank E. Atalan and S. Ozdemir€ at Bingo€l University, and E. Necip Yardım and M. C© i©cek at Mu©s Alparslan University, for facilitating our research at the campuses, and S. Pamuk at the Bingo€l police headquarters. We thank A. and T. Ozdum€ an, police officers in Bingo€l, for assisting with the field study. For technical assistance, we further acknowledge support from M. Fehr, Y.-J. Lai, and L. Hoffland (NASA Ames Research Center); David Mittlefehldt (NASA JSC); K. Wimmer (Ries Crater Museum); J. Sanchez (Planetary Science Institute); A. Neesemann (Free University Berlin); S. Atanasova-Vladimirova and I. Piroeva (Institute of Physical Chemistry, BAS); and B. Georgieva and V. Strijkova (Institute of Optical Materials and Technologies, BAS). This work was supported by Istanbul University (Project No. 40339 and 58261), the Scientific and Technological Research Council of Turkey (MFAG/113F035), the Swiss National Science foundation (PZ00P2_154874 and NCCR PlanetS), the Ministry of Science and Higher Education of the Russian Federation (Project # 3.1959.2017/4.6), Act 211 of the Government of the Russian Federation, contract ? 02.A03.21.0006, the National Natural Science Foundation of China (41403055), the Simons Foundation (302497), the Academy of Finland (299543), the NASA Cosmochemistry Program (NNX14AM62G), the NASA Emerging Worlds Program (NNX16AD34G), and the NASA NEOO program (NNX14-AR92G). -