Decreased level of nerve growth factor (NGF) and its messenger RNA in the aged rat brain

Lärkfors, Lena; Ebendal, Ted; Whittemore, Scott R.; Persson, Håkan; Hoffer, Barry J.; Olson, Lar̀s

doi:10.1016/0169-328x(87)90044-1

Cited by 228 publications

(68 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Diminished plasticity in aged rats has been reported previously (Scheff et al, 1980) and may reflect a reduction in the ability of neurons to synthesize materials necessary for growth, a modification of the glial reaction, or changes in the target tissue. Previous studies have suggested that alterations in the production of factors necessary to initiate a sprouting response may change with age, however, while some studies have shown that levels of NGF mRNA and protein are decreased in aged rats (Koh and Loy, 1987;Larkfors et al, 1987), others have reported no change (Crutcher and Weingartner, 1991). In addition, levels of mRNA for brain derived neurotrophic factor (BDNF), a trophic factor known to support the survival and outgrowth of basal forebrain cholinergic neurons, and its receptors, trkB, are unchanged in the hippocampal formation during normal aging (Lapchak et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

Lesion-induced sprouting of commissural/associational axons and induction of GAP-43 mRNA in hilar and CA3 pyramidal neurons in the hippocampus are diminished in aged rats

et al. 1995

View full text Add to dashboard Cite

Removal of synaptic connections following a partial deafferentation lesion results in a sprouting of remaining afferents that terminate near the denervated area. However, while the ability to form new synapses in response to injury has been reported in both young and aged rats, previous studies have suggested that the injury-induced response in the hippocampus of aged rats may be delayed and/or not as extensive as compared to young adults. Given that growth associated proteins are central for the regulation of neurite outgrowth during both development and regeneration, we were interested in determining if the magnitude and time course of the sprouting response of hippocampal neurons to deafferentation might correlate with induction of growth associated proteins and whether these parameters could be modulated with age. For our studies we used the Holmes fiber stain to determine the expansion of the C/A fiber plexus following denervation and compared the time course of the sprouting response with that observed by in situ hybridization for the neurite outgrowth proteins, growth associated protein-43 (GAP-43), superior cervical ganglion-10 (SCG-10), and neurofilament-68 (NF-68) at various time points after the lesion for each age group. We found that the commissural/associational (C/A) fiber plexus expanded by 45% in young adult rats at 30 and 45 d postlesion and was accompanied by a significant increase in expression of GAP-43 mRNA in both ipsilateral and contralateral hilar and CA3 pyramidal neurons, the cell bodies of origin for the C/A pathway. In contrast, a dampened sprouting response was observed in aged rats at all time points postlesion and coincided with a lack of induction of any of the growth-associated proteins. These results suggest that GAP-43 is involved in outgrowth of C/A axons in the hippocampus in response to a partial deafferentation lesion. However, factors that stimulate neurite outgrowth and upregulate GAP-43 mRNA in response to a partial deafferentation lesion diminish with age.

show abstract

Section: Discussionmentioning

confidence: 99%

Lesion-induced sprouting of commissural/associational axons and induction of GAP-43 mRNA in hilar and CA3 pyramidal neurons in the hippocampus are diminished in aged rats

et al. 1995

View full text Add to dashboard Cite

show abstract

“…The present study was therefore performed to elucidate the distribution of PGRN throughout the mouse brain using immunohistochemical techniques. We also compared the expression levels of PGRN at the mRNA and protein levels in younger and older animals because the expression of other growth factors, such as nerve growth factor (NGF) and brainderived neurotrophic factor (BDNF), are known to decrease with age [14,15]. …”

mentioning

confidence: 99%

Age-Dependent Changes in Progranulin Expression in the Mouse Brain

et al. 2011

View full text Add to dashboard Cite

Abstract. The progranulin (PGRN) gene is involved in sexual differentiation of the brain during the perinatal period and estrogen-induced adult neurogenesis in the hippocampus. Mutations in the PGRN gene are also implicated in human frontotemporal lobar degeneration. Thus, while PGRN appears to play important roles as a growth factor in the brain, the localization of PGRN-expressing cells throughout the brain has not been fully established. In the present study, we examined the localization of PGRN proteins in the brain using adult male wild-type mice and PGRNdeficient mice we had generated previously. We also evaluated age-dependent changes in PGRN expression at the mRNA and protein levels. As expected, no immunoreactivity was observed in the brains of the PGRN-deficient mice. In the wild-type mice, intense immunoreactivity was observed in several brain regions including the cingulate and piriform cortices, the pyramidal cell layer and dentate gyrus of the hippocampus, the amygdala, the ventromedial and arcuate nuclei of the hypothalamus and the Purkinje cell layer in the cerebellum. Moreover, PGRN mRNA and protein expression decreased in the cortex, hippocampus and hypothalamus in an age-dependent manner. Since many of these brain regions are involved in emotion, memory and recognition, PGRN may play roles as a growth factor in these brain functions that decline with age. Key words: Aging, Brain, Gene expression, Immunohistochemistry, Progranulin (J. Reprod. Dev. 57: [113][114][115][116][117][118][119] 2011) he progranulin (PGRN) gene spans approximately 6.3 kbp and encodes a 68.5-kDa protein containing 7.5 tandem granulin motif repeats [1]. PGRN mRNA is expressed in various tissues and organs, including the reproductive organs, gastrointestinal tract, endocrine organs and neural tissues [2,3]. The PGRN protein is processed into peptides of approximately 6 kDa called granulins [2,4], also known as epithelins [5]. Although both PGRN and granulins have growth-modulating effects on many types of cells in culture [4,5], little is known about their precise molecular mechanisms of action.We have identified PGRN as one of the genes that are upregulated in the hypothalamus by sex steroids during the perinatal period and are involved in sexual differentiation of the rat brain [6][7][8][9]. In addition, we also suggested that PGRN plays a role in mediating the mitogenic effects of estrogen in the hippocampus of adult rats [10]. Subsequently, we generated a line of mice lacking the PGRN gene and found that PGRN-deficient mice exhibited enhanced anxiety and decreased male sexual behavior, suggesting that PGRN is indeed involved in masculinization of the rodent brain [11]. Recently, PGRN has been identified as one of the major factors causing frontotemporal lobar degeneration (FTLD) in humans. In studies on the frequency of mutations in the FTLD population, 5-10% of the patients were found to have mutations in the PGRN gene [12,13]. Taken together, these observations suggest that PGRN plays important roles in the brain ...

show abstract

“…NGF and its mRNA content in the hippocampus are reported to be decreased in aged (28 months old) rats [47]. Moreover, LNGFRLIS was shown to be induced by NGF [48].…”

Section: Discussionmentioning

confidence: 99%

Changes in NGF Receptor-Like Immunoreactive Substance in the Suprachiasmatic Nucleus of the Hypothalamus in Blind Rats.

Asada

Nonomura

Nakagawa

1992

J. Clin. Biochem. Nutr.

View full text Add to dashboard Cite

Summaryin mammals, the hypothalamic suprachiasmatic nucleus (SCN ), a circadian oscillator, receives the retinohypothalamic tract (RHT), which is essential for the synchronization of circadian rhythms by light-dark cycle; and nerve growth factor (NGF) receptors with low affinity have been detected in the SCN. Thus, we examined whether low-affinity NGF receptors (LNGFR) are present in the terminals of the RHT by studies on the LNGFR-like immunoreactive substance (LNGFRLIS) in the SCN of blind rats. LNGFRLIS in the SCN gradually decreased with age in control rats, though it could be observed until 16-20 weeks of age. After bilateral orbital enucleation of 4-week-old rats, the density of the LNGFRLIS gradually decreased on both sides of the SCN from week 4 after the operation, disappearing 7 weeks after the operation. In congenitally blind, hereditary microphthalmic rats, LNGFRLIS was not detectable in the SCN, but in half-blind hereditary microphthalmic rats LNGFRLIS was detectable on both sides of the SCN. 125I-NGF injected into the SCN was found in the optic nerve and the retina. Since NGF is suggested to be retrogradely transported and to support survival of neurons, these findings suggest that LNGFR is present at the terminal of the RHT, and raise the possibility that NGF or other growth factors such as brain-derived neurotrophic factor in or around the SCN plays a role in maintaining the retinal ganglion cells through LNGFR.

show abstract

Decreased level of nerve growth factor (NGF) and its messenger RNA in the aged rat brain

Cited by 228 publications

References 37 publications

Lesion-induced sprouting of commissural/associational axons and induction of GAP-43 mRNA in hilar and CA3 pyramidal neurons in the hippocampus are diminished in aged rats

Lesion-induced sprouting of commissural/associational axons and induction of GAP-43 mRNA in hilar and CA3 pyramidal neurons in the hippocampus are diminished in aged rats

Age-Dependent Changes in Progranulin Expression in the Mouse Brain

Changes in NGF Receptor-Like Immunoreactive Substance in the Suprachiasmatic Nucleus of the Hypothalamus in Blind Rats.

Contact Info

Product

Resources

About