Göran Possnert

Dynamics of Hippocampal Neurogenesis in Adult Humans

Adult-born hippocampal neurons are important for cognitive plasticity in rodents. There is evidence for hippocampal neurogenesis in adult humans, although whether its extent is sufficient to have functional significance has been questioned. We have assessed the generation of hippocampal cells in humans by measuring the concentration of nuclear-bomb-test-derived ¹⁴C in genomic DNA, and we present an integrated model of the cell turnover dynamics. We found that a large subpopulation of hippocampal neurons constituting one-third of the neurons is subject to exchange. In adult humans, 700 new neurons are added in each hippocampus per day, corresponding to an annual turnover of 1.75% of the neurons within the renewing fraction, with a modest decline during aging. We conclude that neurons are generated throughout adulthood and that the rates are comparable in middle-aged humans and mice, suggesting that adult hippocampal neurogenesis may contribute to human brain function.

Synchronized terrestrial-atmospheric deglacial records around the North Atlantic

On the basis of synchronization of three carbon-14 (14C)-dated lacustrine sequences from Sweden with tree ring and ice core records, the absolute age of the Younger Dryas-Preboreal climatic shift was determined to be 11,450 to 11,390 ± 80 years before the present. A 150-year-long cooling in the early Preboreal, associated with rising Δ14C values, is evident in all records and indicates an ocean ventilation change. This cooling is similar to earlier deglacial coolings, and box-model calculations suggest that they all may have been the result of increased freshwater forcing that inhibited the strength of the North Atlantic heat conveyor, although the Younger Dryas may have begun as an anomalous meltwater event.

Neurogenesis in the Striatum of the Adult Human Brain

In most mammals, neurons are added throughout life in the hippocampus and olfactory bulb. One area where neuroblasts that give rise to adult-born neurons are generated is the lateral ventricle wall of the brain. We show, using histological and carbon-14 dating approaches, that in adult humans new neurons integrate in the striatum, which is adjacent to this neurogenic niche. The neuronal turnover in the striatum appears restricted to interneurons, and postnatally generated striatal neurons are preferentially depleted in patients with Huntingtons disease. Our findings demonstrate a unique pattern of neurogenesis in the adult human brain.

Dynamics of Cell Generation and Turnover in the Human Heart

The contribution of cell generation to physiological heart growth and maintenance in humans has been difficult to establish and has remained controversial. We report that the full complement of cardiomyocytes is established perinataly and remains stable over the human lifespan, whereas the numbers of both endothelial and mesenchymal cells increase substantially from birth to early adulthood. Analysis of the integration of nuclear bomb test-derived (14)C revealed a high turnover rate of endothelial cells throughout life (>15% per year) and more limited renewal of mesenchymal cells (<4% per year in adulthood). Cardiomyocyte exchange is highest in early childhood and decreases gradually throughout life to <1% per year in adulthood, with similar turnover rates in the major subdivisions of the myocardium. We provide an integrated model of cell generation and turnover in the human heart.

Dynamics of human adipose lipid turnover in health and metabolic disease

Adipose tissue mass is determined by the storage and removal of triglycerides in adipocytes. Little is known, however, about adipose lipid turnover in humans in health and pathology. To study this in vivo, here we determined lipid age by measuring 14C derived from above ground nuclear bomb tests in adipocyte lipids. We report that during the average ten-year lifespan of human adipocytes, triglycerides are renewed six times. Lipid age is independent of adipocyte size, is very stable across a wide range of adult ages and does not differ between genders. Adipocyte lipid turnover, however, is strongly related to conditions with disturbed lipid metabolism. In obesity, triglyceride removal rate (lipolysis followed by oxidation) is decreased and the amount of triglycerides stored each year is increased. In contrast, both lipid removal and storage rates are decreased in non-obese patients diagnosed with the most common hereditary form of dyslipidaemia, familial combined hyperlipidaemia. Lipid removal rate is positively correlated with the capacity of adipocytes to break down triglycerides, as assessed through lipolysis, and is inversely related to insulin resistance. Our data support a mechanism in which adipocyte lipid storage and removal have different roles in health and pathology. High storage but low triglyceride removal promotes fat tissue accumulation and obesity. Reduction of both triglyceride storage and removal decreases lipid shunting through adipose tissue and thus promotes dyslipidaemia. We identify adipocyte lipid turnover as a novel target for prevention and treatment of metabolic disease.

Dynamics of Oligodendrocyte Generation and Myelination in the Human Brain

The myelination of axons by oligodendrocytes has been suggested to be modulated by experience, which could mediate neural plasticity by optimizing the performance of the circuitry. We have assessed the dynamics of oligodendrocyte generation and myelination in the human brain. The number of oligodendrocytes in the corpus callosum is established in childhood and remains stable after that. Analysis of the integration of nuclear bomb test-derived (14)C revealed that myelin is exchanged at a high rate, whereas the oligodendrocyte population in white matter is remarkably stable in humans, with an annual exchange of 1/300 oligodendrocytes. We conclude that oligodendrocyte turnover contributes minimally to myelin modulation in human white matter and that this instead may be carried out by mature oligodendrocytes, which may facilitate rapid neural plasticity.

Quantitative mass and energy dispersive elastic recoil spectrometry: Resolution and efficiency considerations

A time of flight-energy recoil telescope system for mass and energy dispersive recoil spectrometry has been applied to study the formation of Mg2Si layers and depth profiling of Ga1−xAlxAs quantum well structures. Measurements of the energy (depth) dependence of the mass resolution showed that the telescope could be used over the energy range from 5 to 18 MeV to distinguish between recoils of 1 amu mass difference up to mass 28 amu. The energy dependence of the detection efficiency was found to be independent of the recoil energy for 12C and 28Si recoils and no strong evidence for a recoil species dependence of the detection efficiency for recoils heavier than 16O was found.

A calendar age estimate of the Younger Dryas-Holocene boundary at Kråkenes, western Norway

The Younger Dryas/Holocene transition (YD/H) in the sediments of Kråkenes Lake, western Nor way, is well marked both lithologically and palaeobiologically at 756.5 cm in the investigated core. A series of 70 AMS radiocarbon dates on terrestrial plant macrofossils and the NaOH-soluble fraction of lake sediment was measured between 585 and 840 cm, covering the time span c. 10 440 to 7915 BP on the radiocarbon timescale. Forty-three of these dates above 760 cm were wiggle-matched against the German oak-pine dendro calibration curve (IntCal 93) with recent corrections in both the oak and the pine sections. With an increase in age of the pine dendro-series of 200 6 20 yr, the calendar age of the YD/H lithostratigraphic boundary at Kråkenes is estimated to 11 530+40 -60 cal. BP. By using a date of 9750 BP (11 170 cal. BP) on the transition between the 10 000 and 9600 14C plateaux as a time marker, this result is compared with recent results from other archives. It is consistent with many of them, including the GRIP ice core, German pine series, Lake Gościaz, south Swedish lakes, and Baltic varves, suggesting that the Younger Dryas-Holocene transition in the North Atlantic region occurred within the range 11 500–11 600 cal. BP.

Pitfalls in the AMS radiocarbon-dating of terrestrial macrofossils

The AMS 14 C technique has the advantage that small samples of Late Quaternary age can be dated with high accuracy, and that errors due to reservoir effects can be avoided if specifically determined terrestrial micro- and macrofossils are measured. However, to obtain such high-accuracy measurements, it is important how small samples are handled prior to treatment in the radiocarbon laboratories. Here we present a set of 51 AMS 14 C measurements, of which 31 dates gave expected ages and 20 dates resulted in anomalously young ages, despite the fact that all samples consisted of clearly identified Late Weichselian terrestrial plant macrofossils. To evaluate possible sources of error, we compared these samples in respect to preparation methods, sample storage and sample weight. Our results show that the long-term storage of wet macrofossil samples appears to have a significant effect on the radiocarbon age obtained, even when the samples are kept cool. Fungi or micro-organisms may easily be incorporated into a sample during preparation and identification, and can easily contribute to the contamination of a sample, if stored cool and wet for several months.

A molecular analysis of ground sloth diet through the last glaciation

DNA was extracted from five coprolites, excavated in Gypsum Cave, Nevada and radiocarbon dated to approximately 11 000, 20 000 and 28 500 years bp. All coprolites contained mitochondrial DNA sequences identical to a DNA sequence determined from a bone of the extinct ground sloth Nothrotheriops shastensis. A 157‐bp fragment of the chloroplast gene for the large subunit of the ribulosebisphosphate carboxylase (rbcL) was amplified from the boluses and several hundred clones were sequenced. In addition, the same DNA fragment was sequenced from 99 plant species that occur in the vicinity of Gypsum Cave today. When these were compared to the DNA sequences in GenBank, 69 were correctly (two incorrectly) assigned to taxonomic orders. The plant sequences from the five coprolites as well as from one previously studied coprolite were compared to rbcL sequences in GenBank and the contemporary plant species. Thirteen families or orders of plants that formed part of the diet of the Shasta ground sloth could be identified, showing that the ground sloth was feeding on trees as well as herbs and grasses. The plants in the boluses further indicate that the climate 11 000 years bp was dryer than 20 000 and 28 500 years bp. However, the sloths seem to have visited water sources more frequently at 11 000 bp than at earlier times.