Two Genetic Rat Models of Arterial Hypertension Show Different Mechanisms by Which Adult Hippocampal Neurogenesis Is Increased

Kronenberg, Golo; Lippoldt, Andrea; Kempermann, Gerd

doi:10.1159/000096217

Cited by 33 publications

(21 citation statements)

References 102 publications

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“…This result concurs with previous studies which found that neurogenesis dramatically declined in the dentate gyrus during aging [5,7,11,12,17,23,25,28]. In addition, Kronenberg et al [16] compared young adult SHR and stroke-prone SHR (SHRSP) with the genetic control WKY strain: in both SHR and SHRSP, newly generated DCX immunoreactive neurons were significantly high compared to WKY strain. However, in the present study, we found that the number of DCX immunoreactive cells, the intensity of DCX immunoreactivity and the expression level of DCX protein in the SHRs were higher than those in the SDRs at corresponding age stages.…”

Section: Discussionsupporting

confidence: 91%

Doublecortin-Immunoreactive Neuronal Precursors in the Dentate Gyrus of Spontaneously Hypertensive Rats at Various Age Stages: Comparison with Sprague-Dawley Rats

Hwang

Yoon

Choi

et al. 2008

The Journal of Veterinary Medical Science

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ABSTRACT. Spontaneously hypertensive rats (SHRs) are widely accepted in medical research because this model has been used for studies in neurodegenerative diseases such as vascular dementia and stroke. In the present study, we observed newly generated neuronal precursors using doublecortin (DCX, a marker of neural proliferation and differentiation) in the subgranular zone of the dentate gyrus in SHRs compared to Sprague-Dawley rats (SDRs) at various age stages. DCX immunoreactivity, immunoreactive cell numbers and its protein level in the dentate gyrus of the SHRs were higher than those in the SDRs at postnatal month 1 (PM 1). At PM 8, DCX immunoreactivity, immunoreactive cell numbers and protein levels in both groups were markedly decreased compared to those at PM 1; however, they were higher than those in the SDRs. They were decreased in the both groups with age: DCX immunoreactive cells in the SDRs were few at PM 12. Our results indicate that newly generated neuronal precursors are more abundant in SHRs than in SDRs during their life. KEY WORDS: development, doublecortin, neurogenesis, spontaneously hypertensive rat.J. Vet. Med. Sci. 70(4): 373-377, 2008 Spontaneously hypertensive rats (SHRs) are normotensive at birth and gradually develop stable hypertension during the first months of life. These rats are used as a genetic model of hypertension, which is widely accepted in medical research because it has features in common with idiopathic hypertension in man [20,21]. Moreover, this animal model has been used recently in studies of neurodegenerative diseases, such as, vascular dementia and stroke, because hypertension is a primary risk factor of these conditions [9,10].It has been reported that the rate of granule cell generation in the dentate gyrus of the adult mouse is dependent on strain [14,15]. In addition, significantly more newly generated cells and greater proliferation were found in the dentate gyrus of the young SHRs than in the young Sprague-Dawley rats (SDRs) [22]. However, they examined newly generated cells in the dentate gyrus using the thymidine analog bromodeoxyuridine (BrdU), which is labeled on newly generated glial cells as well as neuronal precursors [18].DCX gene encodes a 40-kDa microtubule-associated protein, which is specifically expressed in neuronal precursors in the developing and adult CNS. It is known that during CNS development DCX expression is associated with the migration and differentiation of neuronal precursors [3,4,13], and as a result, DCX is frequently used as a marker of newly generated neurons, not glial cells. In the present study, we investigated differences in distribution of DCX immunoreactive neuronal precursors in the dentate gyrus of SHRs and SDRs at various age stages. MATERIALS AND METHODSExperimental animals: Male SHRs and SDRs were obtained from the Experimental Animal Center, Hallym University, Chuncheon, South Korea. Postnatal month 1 (PM 1) (n=12), PM 8 (n=12) and PM 12 (n=12) rats in each strain were housed in a conventional state under adequate tem...

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Section: Discussionsupporting

confidence: 91%

Doublecortin-Immunoreactive Neuronal Precursors in the Dentate Gyrus of Spontaneously Hypertensive Rats at Various Age Stages: Comparison with Sprague-Dawley Rats

Hwang

Yoon

Choi

et al. 2008

The Journal of Veterinary Medical Science

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“…Higher glucocorticoid levels and reduced 5-HT signaling [Veenema et al, 2003[Veenema et al, , 2004Veenema and Neumann, 2007] in the LAL mice might be contributing to this difference. Genetic influence on hippocampal neurogenesis has also been shown in several other studies [Hayes and Nowakowski, 2002;Kempermann and Gage, 2002;Schauwecker, 2006;Kronenberg et al, 2007]. The observation that social stress affects neurogenesis [Gould et al, 1997] and structural plasticity in the brain [Magarinos et al, 1996;Fuchs and Flügge, 2003] has received wide attention, but the possible interaction between these effects and pre-existing differences in stress coping style is less studied.…”

Section: Linking Physiological Behavioral and Cognitive Traits -Possmentioning

confidence: 79%

Social Regulation of Neurogenesis in Teleosts

et al. 2007

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Salmonid fishes such as the rainbow trout (Oncorhynchus mykiss) are frequently used to study behavioral and neuroendocrine effects of socially induced stress. A predictable aggressive response to territorial intrusion, a well described neuroanatomy, and many essential similarities in the stress response in fishes and other vertebrates are among the advantages of this comparative model. One conspicuous difference when compared to mammals, however, is that in telost fish and other non-mammalian vertebrates, neurogenesis persists into adulthood to a much higher degree. Very little is known about the functional significance of individual differences in the rate of brain cell proliferation in fish, or whether structural changes in the fish brain are influenced by the social environment. In this paper we discuss the observation that brain cell proliferation is reduced in subordinate fish, focusing in particular on whether such individual variation reflects a difference in coping style or is indeed a response to social interactions.

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“…Hippocampal cell counts were determined in one-in-six series of sections covering the entire hippocampus in its rostrocaudal extension as described previously (Kronenberg et al, , 2007. Briefly, cells located in the granule cell layer and adjacent subgranular zone, defined as a two-cell bodies-wide zone of the hilus along the base of the granule cell layer were counted (Brown et al, 2003 Synaptosomes were prepared as described previously (Fink et al, 2002a,b) from the neocortex or hippocampus of adult Gsn ϩ/ϩ or Gsn Ϫ/Ϫ mice.…”

Section: Quantification and Imagingmentioning

confidence: 99%

“…DCX-immunoreactive cells and the number of CR-immunoreactive cells were used as surrogate markers of neurogenesis (Fig. 2C,D) (Kempermann et al, 2004;Kronenberg et al, 2007Kronenberg et al, , 2008. Both the number of DCX ϩ cells and the number of CR ϩ cells were robustly increased in gelsolin-deficient animals compared with wild-type controls (Fig.…”

Section: The Increase In Hippocampal Neurogenesis Is Preserved In Agementioning

confidence: 99%

Impact of Actin Filament Stabilization on Adult Hippocampal and Olfactory Bulb Neurogenesis

Kronenberg¹,

Gertz²,

Baldinger³

et al. 2010

J. Neurosci.

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Rearrangement of the actin cytoskeleton is essential for dynamic cellular processes. Decreased actin turnover and rigidity of cytoskeletal structures have been associated with aging and cell death. Gelsolin is a Ca 2ϩ -activated actin-severing protein that is widely expressed throughout the adult mammalian brain. Here, we used gelsolin-deficient (Gsn Ϫ/Ϫ ) mice as a model system for actin filament stabilization. In Gsn Ϫ/Ϫ mice, emigration of newly generated cells from the subventricular zone into the olfactory bulb was slowed. In vitro, gelsolin deficiency did not affect proliferation or neuronal differentiation of adult neural progenitors cells (NPCs) but resulted in retarded migration. Surprisingly, hippocampal neurogenesis was robustly induced by gelsolin deficiency. The ability of NPCs to intrinsically sense excitatory activity and thereby implement coupling between network activity and neurogenesis has recently been established. Depolarization-induced [Ca 2ϩ ] i increases and exocytotic neurotransmitter release were enhanced in Gsn Ϫ/Ϫ synaptosomes. Importantly, treatment of Gsn Ϫ/Ϫ synaptosomes with mycotoxin cytochalasin D, which, like gelsolin, produces actin disassembly, decreased enhanced Ca 2ϩ influx and subsequent exocytotic norepinephrine release to wild-type levels. Similarly, depolarization-induced glutamate release from Gsn Ϫ/Ϫ brain slices was increased. Furthermore, increased hippocampal neurogenesis in Gsn Ϫ/Ϫ mice was associated with a special microenvironment characterized by enhanced density of perfused vessels, increased regional cerebral blood flow, and increased endothelial nitric oxide synthase (NOS-III) expression in hippocampus. Together, reduced filamentous actin turnover in presynaptic terminals causes increased Ca 2ϩ influx and, subsequently, elevated exocytotic neurotransmitter release acting on neural progenitors. Increased neurogenesis in Gsn Ϫ/Ϫ hippocampus is associated with a special vascular niche for neurogenesis.

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Two Genetic Rat Models of Arterial Hypertension Show Different Mechanisms by Which Adult Hippocampal Neurogenesis Is Increased

Cited by 33 publications

References 102 publications

Doublecortin-Immunoreactive Neuronal Precursors in the Dentate Gyrus of Spontaneously Hypertensive Rats at Various Age Stages: Comparison with Sprague-Dawley Rats

Doublecortin-Immunoreactive Neuronal Precursors in the Dentate Gyrus of Spontaneously Hypertensive Rats at Various Age Stages: Comparison with Sprague-Dawley Rats

Social Regulation of Neurogenesis in Teleosts

Impact of Actin Filament Stabilization on Adult Hippocampal and Olfactory Bulb Neurogenesis

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