Decrease in PTEN and increase in Akt expression and neuron size in aged rat spinal cord

Amorim, Miguel A.R.; Garcia-Segura, Luis Miguel; Goya, Rodolfo G.; Portiansky, Enrique Leo

doi:10.1016/j.exger.2010.03.015

Cited by 13 publications

(9 citation statements)

References 24 publications

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“…With aging, there is thought to be a decline in motor unit number, but a compensatory increase in collateral axonal and terminal sprouting, resulting in an increase in motor unit size (Deschenes, et al, 2010;McNeil, et al, 2005;Vandervoort, 2002). Studies of lower motor neurons in aging humans and rodents have identified alterations to the cell soma size (Miyata, et al, 2008;Rodrigues de Amorim, et al, 2010), degeneration of dendritic and axonal integrity or number (Miyata, et al, 2008), alterations in protein expression (Finazzo, 1994;Hideyama, et al, 2012;Portiansky, et al, 2006;Rodrigues de Amorim, et al, 2010;Rygiel, et al, 2014;Vogelsberg, et al, 1997;Xie, et al, 2000), as well as changes in electrochemical properties and motor neuron firing rates (Christie and Kamen, 2006;Kalmar, et al, 2009;Kamen, et al, 1995;Kido, et al, 2004;Tracy, et al, 2005). However, the literature is not consistent regarding the effects of age on motor neuron number with some studies reporting no change (Chai, et al, 2011;Chopek and Gardiner, 2010), and others indicating substantial loss (Hashizume, et al, 1988;Ishihara, et al, 1987;Jacob, 1998;Kanda, 2002;Lexell, 1997;Tomlinson and Irving, 1977;Xie, et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Perturbed cholesterol homeostasis in aging spinal cord

Parkinson

Dayas

2016

Neurobiology of Aging

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The spinal cord is vital for the processing of sensorimotor information and for its propagation to and from both the brain and the periphery. Spinal cord function is affected by aging, however, the mechanisms involved are not well-understood. To characterize molecular mechanisms of spinal cord aging, microarray analyses of gene expression were performed on cervical spinal cords of aging rats. Of the metabolic and signaling pathways affected, cholesterol-associated pathways were the most comprehensively altered, including significant downregulation of cholesterol synthesis-related genes and upregulation of cholesterol transport and metabolism genes. Paradoxically, a significant increase in total cholesterol content was observed-likely associated with cholesterol ester accumulation. To investigate potential mechanisms for the perturbed cholesterol homeostasis, we quantified the expression of myelin and neuroinflammation-associated genes and proteins. Although there was minimal change in myelin-related expression, there was an increase in phagocytic microglial and astrogliosis markers, particularly in the white matter. Together, these results suggest that perturbed cholesterol homeostasis, possibly as a result of increased inflammatory activation in spinal cord white matter, may contribute to impaired spinal cord function with aging.

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Section: Introductionmentioning

confidence: 99%

Perturbed cholesterol homeostasis in aging spinal cord

Parkinson

Dayas

2016

Neurobiology of Aging

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“…Our data also suggest that cytoplasmatic accumulation of lipofuscin pigments in aged neurons [7] while apparently devoid of toxic effects, may contribute to increasing cell size. As mentioned above, the expression of PTEN, a tumor suppressor gene known to play an important role in the regulation of cell size, has been shown to decrease in the spinal cord of aging rats [10] . This decrease may play a role in the age-related increase in neuronal size reported here.…”

Section: Discussionmentioning

confidence: 92%

“…In fact, there is scarce information even on the general morphological changes in the spinal cord of aging rats. In previous studies we have observed that there is an increase in the number of neurofilaments present in the gray matter of aged rats [7] , changes in the lectinhistochemical pattern [8] , a complete loss of neuron-specific nuclear protein (NeuN) immunoreactivity in cervical, thoracic and lumbar segments of aged female rats [9] , as well as a decrease in the expression of a phosphatase and tensin homologue on chromosome 10 (PTEN), a tumor suppressor gene known to play an important role in the regulation of cell size [10] .…”

Section: Introductionmentioning

confidence: 99%

Increased Number of Neurons in the Cervical Spinal Cord of Aged Female Rats

et al. 2011

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In the brain, specific signaling pathways localized in highly organized regions called niches allow the persistence of a pool of stem and progenitor cells that generate new neurons in adulthood. Much less is known about the spinal cord where a sustained adult neurogenesis is not observed. Moreover, there is scarce information concerning cell proliferation in the adult mammalian spinal cord and virtually none in aging animals or humans. We performed a comparative morphometric and immunofluorescence study of the entire cervical region (C1-C8) in young (5 mo.) and aged (30 mo.) female rats. Serum prolactin (PRL), a neurogenic hormone, was also measured. Gross anatomy showed a significant age-related increase in size of all of the cervical segments. Morphometric analysis of cresyl violet stained segments also showed a significant increase in the area occupied by the gray matter of some cervical segments of aged rats. The most interesting finding was that both the total area occupied by neurons and the number of neurons increased significantly with age, the latter increase ranging from 16% (C6) to 34% (C2). Taking the total number of cervical neurons the age-related increase ranged from 19% (C6) to 51% (C3), C3 being the segment that grew most in length in the aged animals. Some bromodeoxyuridine positive-neuron specific enolase negative (BrdU+-NSE−) cells were observed and, occasionally, double positive (BrdU+-NSE+) cells were detected in some cervical segments of both young and aged rats groups. As expected, serum PRL increased markedly with age. We propose that in the cervical spinal cord of female rats, both maturation of pre-existing neuroblasts and/or possible neurogenesis occur during the entire life span, in a process in which PRL may play a role.

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“…Recently, aging in the normal brain and spinal cord has been associated with moderate degrees of neurochemical changes, structural derangement and neuronal damage [13][14][15][16]. There are some reports about age-related changes of aII-spectrin proteolysis in the hippocampus [17,18] and in some motor neurons which show apoptosis in the aged rat lumbar enlargement through a caspase-dependent manner [19].…”

Section: Introductionmentioning

confidence: 97%

Increased Immunoreactivities of Cleaved αII-Spectrin and Cleaved Caspase-3 in the Aged Dog Spinal Cord

et al. 2011

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The activation of caspase-3 is considered to be a reliable marker for apoptotic cell death, and a 120-kDa fragment of αII-spectrin is generated by caspase-3 mediated cleavage of this structural protein. In the present study, we compared cleaved αII-spectrin (120-kDa) and cleaved caspase-3-immunoreactive cells and their protein levels in the cervical (C₅-C₆) and lumbar (L₃-L₄) levels of the spinal cord in adult (1-2 year-old) and aged (10-12 year-old) dogs (German shepherds). Weak cleaved αII-spectrin and cleaved caspase-3 immunoreactivity was found in neurons of the adult group; however, their immunoreactivity was distinctively increased in the neuronal cytoplasm in the aged group compared to those in the adult group, although the distribution pattern of their neurons was similar between the adult and age group. In addition, cleaved αII-spectrin and cleaved caspase-3 levels in the aged spinal cord were markedly increased compared to those in the adult group. These findings suggest that the increases of cleaved αII-spectrin and cleaved caspase-3 immunoreactivity may be related to aging of the spinal cord in dogs.

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Decrease in PTEN and increase in Akt expression and neuron size in aged rat spinal cord

Cited by 13 publications

References 24 publications

Perturbed cholesterol homeostasis in aging spinal cord

Perturbed cholesterol homeostasis in aging spinal cord

Increased Number of Neurons in the Cervical Spinal Cord of Aged Female Rats

Increased Immunoreactivities of Cleaved αII-Spectrin and Cleaved Caspase-3 in the Aged Dog Spinal Cord

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