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

Abstract

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...

Comparison of Ionized Calcium-binding Adapter Molecule 1-Immunoreactive Microglia in the Spinal Cord Between Young Adult and Aged Dogs

“…Because aging is a major risk factor for major CNS disorders, the cellular and molecular changes that occur during aging and the factors that can extend lifespan have been studied [19][20][21]. In this study, we compared NeuN-immunoreactive neurons in the each level of the spinal cord between the adult and aged dogs: The number of NeuN-immunoreactive neurons was not significantly changed between the groups.…”

Neuronal changes after chronic high blood pressure in animal models and its implication for vascular dementia

“…The SH rats also showed spatial memory deficits with a reduction of white matter volumes (for review see Kaiser et al, 2014), loss of neurons and gial reaction (for review see Tayebati et al, 2012). Therefore, the SH rats have been used recently in studies of neurodegenerative diseases, such as VD (for review see Hwang et al, 2007). In addition, the neuro-histopathological changes reported in the SH rats include chronical vessel changes with stroke lesions, mainly hemorrhagic episodes in the cerebral cortex and basal ganglia (Hainsworth and Markus, 2008;Jiwa et al, 2010).…”

The Effect of Hypertension on Adult Hippocampal Neurogenesis in Young Adult Spontaneously Hypertensive Rats and Dahl Rats

“…Kronenberg and colleagues (2007) showed an increase in the number of DCX+ and BrdU+ cells in the DG both in SHR hypertensive strain and SHR strokeprone hypertensive strain compared to their genetic control Wistar Kyoto rats. Hwang et al (2008) measured proliferation using the number of DCX+ cells at various ages (1, 8 and 12 months) in SHRs compared to SD rats. At all ages the number of DCX+ cells in the DG was higher in SHRs.…”

“…Importantly, hypertension can lead to the impairments in hippocampus-dependent processes such as learning and spatial orientation, even in the absence of clinical evidence of vascular damage (Harrington et al 2000, Papademetriou 2005. Studies show that hypertension decreases (Pietranera et al 2006, Pietranera et al 2008, Pietranera et al 2010, Shih et al 2016 but also increases (Hwang et al 2008, Kronenberg et al 2007, Perfilieva et al 2001 adult neurogenesis. Thus question remains, however, if hippocampal sensitivity to blood pressure also includes alterations of adult neurogenesis in the dentate gyrus (DG).…”