Cerebral Cortex Gsα Protein Levels and Forskolin-Stimulated Cyclic AMP Formation Are Increased in Bipolar Affective Disorder

Abstract: Experimental animal and peripheral blood cell studies point to guanine nucleotide regulatory (G) protein disturbances in bipolar affective disorder. We have previously reported elevated prefrontal cortex G_sα protein in bipolar affective disorder and have now extended these preliminary observations in a larger number of subjects, assessing the brain regional specificity of these changes in greater detail, determining the functional biochemical correlates of such changes, and evaluating their diagnostic specificity. Membrane G protein (G_sα, G_iα, G_oα, and Gβ) immunoreactivities were estimated by western blotting in postmortem brain regions obtained from 10 patients with a DSMIII-R diagnosis of bipolar affective disorder and 10 nonpsychiatric controls matched on the basis of age, postmortem delay, and brain pH. To examine whether there were functional correlates to the observed elevated G_sα levels, basal and GTPγS-and forskolin-stimulated cyclic AMP production was determined in the same brain regions. Compared with controls, G_sα (52-kDa species) immunoreactivity was significantly (p < 0.05) elevated in prefrontal (+36%), temporal (+65%), and occipital (+96%) cortex but not in hippocampus (+28%), thalamus (-23%), or cerebellum (+21%). In contrast, no significant differences were found in the other G protein subunits (G_iα, G_oα, Gβ) measured in these regions. Forskolin-stimulated cyclic AMP production was significantly increased in temporal (+31%) and occipital (+96%) cortex but not in other regions. No significant differences were apparent in basal or GTPγS-stimulated cyclic AMP production. A significant correlation (r= 0.60, p < 0.001) was observed between forskolin-stimulated cyclic AMP formation and G_sα (52 kDa) immunoreactivity when examined across these cortical regions. The observed increase in G_sα may be specific to bipolar disorders as no significant differences were detected in G_sα levels in temporal cortex from patients with either schizophrenia (n = 7) or Alzheimer's disease (n = 7). In summary, the present study confirms and extends our earlier findings and supports the notion that increased G_sα levels and possibly G_sα-adenylyl cyclase-mediated signal transduction are relevant to the pathophysiology of bipolar affective disorder.     

Size and mortality rates of Glossina pallidipes in the semi-arid zone of southwestern Kenya

Seasonal changes in the mean size of tsetse, Glossina pallidipes Austen, as indicated by wing vein length, were monitored during 1983-86 at Nguruman, southwestern Kenya. Changes in size of nulliparous females and wing fray category 1 males were shown to be correlated with the relative humidity 2 months before they were captured. Soil temperature when flies were in the pupal stage had much less effect. Size dependent mortality was demonstrated, with the mean size of flies emerging from pupae significantly less than that of field-caught flies. This mortality must occur at emergence, since there was no evidence of size-dependent mortality once the flies became available to the trap. Size was correlated with density-independent mortality acting on the parent population 2 months previously. It might therefore be possible to use size as an index of the intensity of such mortality. This could be useful when assessing the level of additional mortality required to suppress tsetse populations.     

Nuclear DNA sequences from late Pleistocene megafauna

We report the retrieval and characterization of multi- and single-copy nuclear DNA sequences from Alaskan and Siberian mammoths (Mammuthus primigenius). In addition, a nuclear copy of a mitochondrial gene was recovered. Furthermore, a 13,000-year-old ground sloth and a 33,000- year-old cave bear yielded multicopy nuclear DNA sequences. Thus, multicopy and single-copy genes can be analyzed from Pleistocene faunal remains. The results also show that under some circumstances, nucleotide sequence differences between alleles found within one individual can be distinguished from DNA sequence variation caused by postmortem DNA damage. The nuclear sequences retrieved from the mammoths suggest that mammoths were more similar to Asian elephants than to African elephants.