| 41. |
- Karlsson, Lars O, 1975, et al.
(författare)
-
Constitutive PGC-1α Overexpression in Skeletal Muscle Does Not Contribute to Exercise-Induced Neurogenesis.
- 2021
-
Ingår i: Molecular neurobiology. - : Springer Science and Business Media LLC. - 1559-1182 .- 0893-7648. ; 58, s. 1465-1481
-
Tidskriftsartikel (refereegranskat)abstract
- Physical exercise can improve age-dependent decline in cognition, which in rodent is partly mediated by restoration of an age-dependent decline in neurogenesis. Exercise-inducible myokines in the circulation present a link in muscle-brain crosstalk. The transcription factor PGC-1α regulates the release of such myokines with neurotrophic properties into the circulation. We study how chronic muscular overexpression of PGC-1α could contribute to exercise-induced effects on hippocampal neurogenesis and if this effect could be enhanced in a running wheel paradigm. We used 3- and 11-month-old transgenic mice with overexpression of PGC-1α under the control of muscle creatinine kinase promoter (MCK-PGC-1α), which have a constitutively developed endurance muscle phenotype. Wild-type and MCK-PGC-1α mice were single housed with free access to running wheels. Four weeks of running in female animals increased the levels of newborn cells, immature neurons, and, for young animals, new mature neurons, compared to sedentary controls. However, no difference in these parameters was observed between wild-type and transgenic mice under sedentary or running conditions. Multiplex analysis of serum cytokines, chemokines, and myokines suggested several differences in serum protein concentrations between genotypes with musclin found to be significantly upregulated 4-fold in male MCK-PGC-1α animals. We conclude that constitutive muscular overexpression of PGC-1α, despite systemic changes and difference in serum composition, does not translate into exercise-induced effects on hippocampal neurogenesis, independent of the age of the animal. This suggests that chronic activation of PGC-1α in skeletal muscle is by itself not sufficient to mimic exercise-induced effects or to prevent decline of neurogenesis in aging.
|
|
| 42. |
- Kempermann, G., et al.
(författare)
-
Human Adult Neurogenesis: Evidence and Remaining Questions
- 2018
-
Ingår i: Cell Stem Cell. - : Elsevier BV. - 1934-5909 .- 1875-9777. ; 23:1, s. 25-30
-
Tidskriftsartikel (refereegranskat)abstract
- Renewed discussion about whether or not adult neurogenesis exists in the human hippocampus, and the nature and strength of the supporting evidence, has been reignited by two prominently published reports with opposite conclusions. Here, we summarize the state of the field and argue that there is currently no reason to abandon the idea that adult-generated neurons make important functional contributions to neural plasticity and cognition across the human lifespan.
|
|
| 43. |
|
|
| 44. |
- Kuhn, Hans-Georg, 1961, et al.
(författare)
-
A lifetime perspective on risk factors for cognitive decline with a special focus on early events
- 2024
-
Ingår i: CEREBRAL CIRCULATION-COGNITION AND BEHAVIOR. - 2666-2450. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Both Alzheimer's disease and vascular dementia are the result of disease processes that typically develop over several decades. Population studies have estimated that more than half of the risk for dementia is preventable or at least modifiable through behavioral adaptations. The association between these lifestyle factors and the risk of dementia is most evident for exposure in midlife. However, habits formed in middle age often reflect a lifetime of behavior patterns and living conditions. Therefore, individuals who, for example, are able to maintain healthy diets and regular exercise during their middle years are likely to benefit from these cognition-protective habits they have practiced throughout their lives. For numerous adult diseases, significant risks can often be traced back to early childhood. Suboptimal conditions during the perinatal period, childhood and adolescence can increase the risk of adult diseases, including stroke, heart disease, insulin resistance, hypertension and dementia. This review aims at summarizing some of the evidence for dementia risks from a life-time perspective with the goal of raising awareness for early dementia prevention and successful aging.
|
|
| 45. |
- Kuhn, Hans-Georg, 1961, et al.
(författare)
-
Adult Hippocampal Neurogenesis: A Coming-of-Age Story
- 2018
-
Ingår i: Journal of Neuroscience. - : Society for Neuroscience. - 0270-6474 .- 1529-2401. ; 38:49, s. 10401-10410
-
Tidskriftsartikel (refereegranskat)abstract
- What has become standard textbook knowledge over the last decade was a hotly debated matter a decade earlier: the proposition that new neurons are generated in the adult mammalian CNS. The early discovery by Altman and colleagues in the 1960s was vulnerable to criticism due to the lack of technical strategies for unequivocal demonstration, quantification, and physiological analysis of newly generated neurons in adult brain tissue. After several technological advancements had been made in the field, we published a paper in 1996 describing the generation of new neurons in the adult rat brain and the decline of hippocampal neurogenesis during aging. The paper coincided with the publication of several other studies that together established neurogenesis as a cellular mechanism in the adult mammalian brain. In this Progressions article, which is by no means a comprehensive review, we recount our personal view of the initial setting that led to our study and we discuss some of its implications and developments that followed. We also address questions that remain regarding the regulation and function of neurogenesis in the adult mammalian brain, in particular the existence of neurogenesis in the adult human brain.
|
|
| 46. |
|
|
| 47. |
- Kuhn, Hans-Georg, 1961
(författare)
-
Control of Cell Survival in Adult Mammalian Neurogenesis
- 2015
-
Ingår i: Cold Spring Harbor Perspectives in Biology. - : Cold Spring Harbor Laboratory. - 1943-0264. ; 7:12
-
Tidskriftsartikel (refereegranskat)abstract
- The fact that continuous proliferation of stem cells and progenitors, as well as the production of new neurons, occurs in the adult mammalian central nervous system (CNS) raises several basic questions concerning the number of neurons required in a particular system. Can we observe continued growth of brain regions that sustain neurogenesis? Or does an elimination mechanism exist to maintain a constant number of cells? If so, are old neurons replaced, or are the new neurons competing for limited network access among each other? What signals support their survival and integration and what factors are responsible for their elimination? This review will address these and other questions regarding regulatory mechanisms that control cell-death and cell-survival mechanisms during neurogenesis in the intact adult mammalian brain.
|
|
| 48. |
|
|
| 49. |
- Kuhn, Hans-Georg, 1961, et al.
(författare)
-
Detection and Phenotypic Characterization of Adult Neurogenesis
- 2016
-
Ingår i: Cold Spring Harbor Perspectives in Biology. - : Cold Spring Harbor Laboratory. - 1943-0264. ; 8:3
-
Tidskriftsartikel (refereegranskat)abstract
- Studies of adult neurogenesis have greatly expanded in the last decade, largely as a result of improved tools for detecting and quantifying neurogenesis. In this review, we summarize and critically evaluate detection methods for neurogenesis in mammalian and human brain tissue. Besides thymidine analog labeling, cell-cycle markers are discussed, as well as cell stage and lineage commitment markers. Use of these histological tools is critically evaluated in terms of their strengths and limitations, as well as possible artifacts. Finally, we discuss the method of radiocarbon dating for determining cell and tissue turnover in humans.
|
|
| 50. |
- Kuhn, Hans-Georg, 1961, et al.
(författare)
-
Developmental dysregulation of adult neurogenesis.
- 2011
-
Ingår i: The European journal of neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 33:6, s. 1115-22
-
Forskningsöversikt (refereegranskat)abstract
- Rather than a singular event that suddenly appears during adulthood, adult neurogenesis has long been recognized as the continuation of postnatal neurogenic activity. During the first postnatal weeks, significant cellular changes occur within and adjacent to germinal matrices of the subventricular zone and dentate gyrus. The majority of granule cells are generated during this period. In addition, radial glia are transformed into astrocyte-like stem cells, the ependymal layer is formed, and the highest rates of angiogenesis, gliogenesis and myelination are observed. The first postnatal weeks are critical as the brain growth rate is maximal, and changes during this period can have a great impact on neurogenesis levels and overall brain function later in life. This review chronicles cellular changes and some of the clinically relevant dysregulations that can occur during the postnatal period, and discusses the possible impact of these changes on neurogenesis and cognitive function later in life.
|
|
