| 1. |
- Berger, Anna-Karin
(författare)
-
Old age depression : occurrence and influence on cognitive functioning in aging and Alzheimer's disease
- 2004
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The general aims of this thesis were to examine the occurrence of depressive symptoms three years before the diagnoses of depression and Alzheimer's disease (AD), and to study the effects of depression on cognitive functioning in aging and AD. Five empirical studies were conducted. All data were taken from the Kungsholmen Project, a longitudinal populationbased study of aging and dementia targeting persons who are 75 years and older, living in the Kungsholmen district in Stockholm, Sweden. The specific objectives of Study I were to examine preclinical markers of depression, in terms of presence and severity of depressive symptoms, as well as to examine whether cognitive deficits were present during the preclinical period of old age depression. The chief aim of Study II was to investigate depressive symptomatology, with respect to mood- or motivation-related symptoms, in the preclinical phase of AD. In particular, Study 11 examined mood- and motivation-related symptoms in relation to subjective memory problems to elucidate whether depressive symptoms reflect insight into the dementing process, or is rather a part of the neurodegenerative process. Study III and IV investigated the influence of depression on AD-related deficits in various cognitive domains (e.g., episodic memory, shortterm memory, verbal abilities, visuospatial skill) in mild to moderate stages of AD, whereas Study V examined the influence of depression on global cognitive functioning longitudinally, from the preclinical stage of AD to the time of diagnosis. Study V also addressed whether a concurrent diagnosis of depression causes more rapid decline in global cognitive functioning over a 3-year interval among persons who were going to develop AD. Findings from Study I showed that depressive symptoms are elevated preclinically in old age depression. Persons who were to be depressed showed a greater number of depressive symptoms (i.e., dysphoria, appetite disturbance) and their symptoms were also more severe (i.e., dysphoria, appetite disturbance, lack of interest, psychomotor disturbances), compared to individuals who remained nondepressed. In addition, depressive symptoms were associated with somewhat poorer global cognitive functioning. These data suggest that there are preclinical markers for old age depression. Study II revealed that depressive symptoms are elevated in preclinical AD as well. There was a predominance of motivation-related (e.g., lack of interest, concentration difficulties, loss of energy) over mood-related (e.g., dysphoria, feelings of guilt, thoughts of death) symptoms. This pattern remained after controlling for subjective memory complaints, indicating that the elevation of depressive symptoms may not merely reflect self-perceived cognitive deficits. Thus, depressive symptoms may be a part of the pathological process of AD. The studies (III and IV) examining the effects of depression on AD-related cognitive deficits showed no impact of depression among mild to moderate cases of AD in episodic memory, verbal ability, and visuospatial skill. However, depressionrelated deficits in global cognitive functioning were observed in the preclinical phase of AD (Study V), although a diagnosis of depression did not result in greater decline over a 3-year follow-up interval. To summarize the findings of this thesis, depressive symptoms were found to be elevated preclinically in both depression and AD. However, different patterns of symptoms were present. Mood-related symptoms were more elevated in depression, whereas motivationrelated symptoms were dominating in AD. In terms of depression-related effects on cognitive functioning in AD, the results indicated that, already at a very early clinical stage of AD, the neurodegenerative process overshadows the impact of depression, although this condition is associated with cognitive deficits in normal aging.
|
|
| 2. |
|
|
| 3. |
- Berger, Karin
(författare)
-
Enterostatin - target proteins and intracellular mechanisms. Function in food intake and energy metabolism
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hunger and satiety are the results of complex neural events that involve several neurotransmitters and peptides. Enterostatin is an appetite-regulating peptide released in the intestine in response to fat ingestion. Enterostatin specifically decreases fat intake, but has also metabolic effects like inhibition of insulin secretion. Enterostatin has both central and gastrointestinal site of action, although the gastrointestinal action is dependent on vagal transmission. The target and cellular mechanisms has however not been elucidated. In this thesis, a possible target protein for enterostatin has been found in a neuronal cell line and further identified in rat brain membranes. The target protein was identified as the beta-subunit of the F1F0-ATP synthase. Furthermore, the binding of enterostatin to the protein was verified in pure F1F0-ATP synthase and was also confirmed in the insulin producing cell line INS-1. In INS-cells, the targeting of enterostatin resulted in perturbed ATP synthesis, enhanced heat production and increased oxygen consumption. Enterostatin was also shown to decrease the insulin secretion in these cells. This indicates that enterostatin is involved in the regulation of energy metabolism within the cell. The binding of enterostatin to F1-ATPase was inhibited by µ-opiates, i.e. beta-casomorphin, but not by a kappa-opiate. The inhibition of high-fat food intake by low doses of intravenous injection of enterostatin was abolished by simultaneous equimolar administration of beta-casomorphin. Higher doses of enterostatin instead increased the high-fat food intake, and there was a synergistic increase on food intake together with beta-casomorphin. The association between insulin secretion and uncoupling protein-2 (UCP2) expression was compared in INS-1 cells after long-term exposure to oleic acid. It was concluded that fatty acid-induced increase in UCP2 expression is not always associated with decreased insulin secretion.
|
|
| 4. |
- Berger, Karin, et al.
(författare)
-
Mitochondrial ATP synthase--a possible target protein in the regulation of energy metabolism in vitro and in vivo
- 2002
-
Ingår i: Nutritional neuroscience. - : Informa UK Limited. - 1028-415X .- 1476-8305. ; 5:3, s. 201-210
-
Tidskriftsartikel (refereegranskat)abstract
- The increasing prevalence of obesity in the Western world has stimulated an intense search for mechanisms regulating food intake and energy balance. A number of appetite-regulating peptides have been identified, their receptors cloned and the intracellular events characterized. One possible energy-dissipating mechanism is the mitochondrial uncoupling of ATP-synthesis from respiratory chain oxidation through uncoupling proteins, whereby energy derived from food could be dissipated as heat, instead of stored as ATP. The exact role of the uncoupling proteins in energy balance is, however, uncertain. We show here that mitochondrial F1F0-ATP synthase itself is a target protein for an anorectic peptide, enterostatin, demonstrated both after affinity purification of rat brain membranes and through a direct physical interaction between enterostatin and purified F1-ATP synthase. In insulinoma cells (INS-1) enterostatin was found to target F1F0-ATP synthase, causing an inhibition of ATP production, an increased thermogenesis and increased oxygen consumption. The experiments suggest a role of mitochondrial F1F0-ATP synthase in the suppressed insulin secretion induced by enterostatin. It could be speculated that this targeting mechanism is involved in the decreased energy efficiency following enterostatin treatment in rat.
|
|
| 5. |
- Noren, L, et al.
(författare)
-
Size or polarisability effects? A comparative study of TlCu7S4 and TlCu7Se4
- 2001
-
Ingår i: JOURNAL OF ALLOYS AND COMPOUNDS. - 0925-8388. ; 314:1-2, s. 114-123
-
Tidskriftsartikel (refereegranskat)abstract
- The room temperature structures of the tetragonal compounds TlCu7S4 and TlCu7Se4 have been reinvestigated on various fronts, by experiment and theoretical calculations. Neutron powder diffraction data have been analysed by Rietveld profile refinement and Reverse Monte Carlo modelling. Both approaches show substantial disorder on the copper site that corresponds to 25% vacancies in the common crystallographic description, and more so inthe thiocuprate than in the selenocuprate.
|
|
| 6. |
|
|
| 7. |
- Rippe, Catarina, et al.
(författare)
-
Effect of high-fat diet, surrounding temperature, and enterostatin on uncoupling protein gene expression
- 2000
-
Ingår i: American Journal of Physiology: Endocrinology and Metabolism. - 1522-1555. ; 279:2, s. 293-300
-
Tidskriftsartikel (refereegranskat)abstract
- Nonshivering thermogenesis induced in brown adipose tissue (BAT) during high-fat feeding is mediated through uncoupling protein 1 (UCP1). UCP2 is a recently identified homologue found in many tissues. To determine the role of UCP1 and UCP2 in thermoregulation and energy balance, we investigated the long-term effect of high-fat feeding on mRNA levels in mice at two different ambient temperatures. We also treated mice with the anorectic peptide enterostatin and compared mRNA levels in BAT, white adipose tissue (WAT), stomach, and duodenum. Here, we report that high-fat feeding at 23 degrees C increased UCP1 and UCP2 levels in BAT four- and threefold, respectively, and increased UCP2 levels fourfold in WAT. However, at 29 degrees C, UCP1 decreased, whereas UCP2 remained unchanged in BAT and increased twofold in WAT. Enterostatin increased UCP1 and decreased UCP2 mRNA in BAT. In stomach and duodenum, high-fat feeding decreased UCP2 mRNA, whereas enterostatin increased it. Our results suggest that the regulation of uncoupling protein mRNA levels by high-fat feeding is dependent on ambient temperature and that enterostatin is able to modulate it.
|
|
| 8. |
- Rippe, Catarina, et al.
(författare)
-
Effect of long-term high-fat feeding on the expression of pancreatic lipases and adipose tissue uncoupling proteins in mice
- 2003
-
Ingår i: Pancreas. - 0885-3177. ; 26:2, s. 36-42
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: A diet containing a high amount of fat has been shown, in short-term studies, to increase the expression of pancreatic lipase and colipase. AIM: To investigate the effects of long-term high-fat-feeding (113 days) on the mRNA expression of pancreatic lipase, colipase, pancreatic lipase-related proteins (1 and 2), and uncoupling proteins during the development of obesity and glucose intolerance. METHODOLOGY: Mice were fed either a high-fat or standard diet and killed after 3, 13, 57, and 113 days. Brown and white adipose tissue and pancreas were collected for mRNA extraction [corrected]. RESULTS: The high-fat-fed mice became obese and glucose-intolerant by 113 days. The high-fat diet increased lipase (p < 0.05) expression initially. At the end of the experiment, the lipase levels had decreased to the level of the control. Colipase levels did not change during the first 57 days of high-fat feeding but decreased below control levels by 113 days (p < 0.05). The high-fat diet increased brown adipose tissue uncoupling protein 1 (UCP1)(p < 0.005) expression but not the expression of uncoupling protein 2. CONCLUSION: Long-term high-fat feeding, leading to glucose intolerance, occurs with a simultaneous decrease in the mRNA expression of pancreatic lipase and colipase and an increase in UCP1 expression.
|
|
