Impact of aging on heat shock protein expression in the substantia nigra and striatum of the female rat

Abstract

Many heat shock proteins are chaperones that help refold or degrade misfolded proteins and battle apoptosis. Because of their capacity to protect against protein misfolding, they may help keep diseases of aging at bay. A few reports have examined heat shock proteins (eg. Hsp25, Hsp60, Hsp70, and heat shock cognate 70 or Hsc70) as a function of age in the striatum and nigra. In the present study, we examined the impact of aging on Hsp25, heme oxygenase 1 (HO1 or Hsp32), Hsp40, Hsp60, Hsc70, Hsc/Hsp70 interacting protein (Hip), 78 kDa glucose-regulated protein (GRP78), Hsp90, and ubiquitinated proteins in the nigra and striatum of the female rat by infrared immunoblotting. Female animals are not typically examined in aging studies, adding further to the novelty of our study. Striatal HO1 and Hsp40 were both higher in middle-aged females than in the oldest group. Hsp60 levels were also highest in middle age in the nigra, but were highest in the oldest animals in the striatum. Striatal levels of Hsc70 and the co-chaperone Hip were lower in the oldest group relative to the youngest animals. In contrast, Hsp25 rose with advancing age in both regions. Hsp25 was also colocalized with tyrosine hydroxylase in nigral neurons. Ubiquitinated proteins exhibited a trend to rise in the oldest animals in both regions, and K48 linkage-specific ubiquitin rose significantly from 4-6 to 16-19 months in the striatum. Our study reveals a complex array of age-related changes in heat shock proteins. Furthermore, the age-related rises in some proteins, such as Hsp25, may reflect endogenous adaptations to cellular stress.

Heat shock protein responses to aging and proteotoxicity in the olfactory bulb

“…We previously found an age‐related loss in Hsc70 in the striatum of female rats (Gleixner et al . ), consistent with this study. Hsc70 levels have also been reported to fall in the temporal cortex in Alzheimer's patients (Yoo et al .…”

Heat shock protein defenses in the neocortex and allocortex of the telencephalon

“…Notably, aged allocortex exhibited lower levels of Hsp90 and CHIP than aged neocortex, an observation that supports further examination of these proteins in relation to diseases associated with aging. Finally, the age- and MG132-related increase in Hsp25 in allocortex is consistent with previous work that this Hsp is higher in the cortex, striatum, substantia nigra, and the olfactory bulb of aged animals relative to young controls (Crum et al, in press; Dickey et al, 2009; Gleixner et al, 2014; Gupte et al, 2010; Schultz et al, 2001). …”

Heat shock proteins in neurodegenerative disorders and aging

“…Most commonly, there appear to be straightforward increases or decreases of heat shock proteins in neurodegenerative conditions and in aging, with the responses varying by heat shock protein, disease, cell type, brain region, etc. However, on occasion we have also observed a somewhat biphasic expression pattern in the heat shock protein response to age-related stress (Gleixner et al 2014). If one assumes that age-related stress accrues over time, our findings bear some resemblance to the biphasic phenomenon of 'hormesis,' defined in the toxicological literature as low dose stimulation and high dose inhibition (Calabrese 2010(Calabrese , 2013Calabrese and Blain 2011;Calabrese et al 2010;Mattson 2008).…”

“…It is instructive that Hsp27 expression increases with the severity of the pathological changes as well as the duration of the disease (Renkawek et al 1993(Renkawek et al , 1994aWilhelmus et al 2006). We and others have reported that Hsp25 is also markedly increased by aging in the striatum, substantia nigra, globus pallidus, and cerebral cortex (Dickey et al 2009;Gleixner et al 2014;Gupte et al 2010). Using immunofluorescent confocal analyses, we also determined that Hsp25 is expressed within tyrosine hydoxylase + dopaminergic neurons in the substantia nigra, pars compacta (Gleixner et al 2014).…”