Gender- and region-specific changes in estrogen signaling in aging rat brain mitochondria

Evola, Christopher M; Hudson, Tanner L; Huang, Lüping; Corbett, Adrian M.; Mayes, Debra A.

doi:10.18632/aging.101538

Cited by 7 publications

(9 citation statements)

References 38 publications

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“…Similar findings were also recently reported [25]. However, a sex-specific difference on PKCs brain distribution with an increase in expression in male brain, which deserves further investigation, has been suggested [25]. Moreover, it was also suggested that this age-related change in their activity and expression may explain, at least in part, an increase of chronic diseases susceptibility in the elderly [26,27].…”

Section: Protein Kinase Cs In Brain and Neurological Diseasessupporting

confidence: 82%

“…A study investigated the cytosolic and particulate fractions of cortex, striatum and hippocampus obtained from young and middle-aged rats showing no significant changes between young and middle-aged animal brains, therefore suggesting the changes in their expression may begin since middle-age and continue in aged brain [24]. Similar findings were also recently reported [25]. However, a sex-specific difference on PKCs brain distribution with an increase in expression in male brain, which deserves further investigation, has been suggested [25].…”

Section: Protein Kinase Cs In Brain and Neurological Diseasessupporting

confidence: 72%

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Age-Dependent Levels of Protein Kinase Cs in Brain: Reduction of Endogenous Mechanisms of Neuroprotection

Pastore

Pacifici

Dave

et al. 2019

IJMS

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Neurodegenerative diseases are among the leading causes of mortality and disability worldwide. However, current therapeutic approaches have failed to reach significant results in their prevention and cure. Protein Kinase Cs (PKCs) are kinases involved in the pathophysiology of neurodegenerative diseases, such as Alzheimer’s Disease (AD) and cerebral ischemia. Specifically ε, δ, and γPKC are associated with the endogenous mechanism of protection referred to as ischemic preconditioning (IPC). Existing modulators of PKCs, in particular of εPKC, such as ψεReceptor for Activated C-Kinase (ψεRACK) and Resveratrol, have been proposed as a potential therapeutic strategy for cerebrovascular and cognitive diseases. PKCs change in expression during aging, which likely suggests their association with IPC-induced reduction against ischemia and increase of neuronal loss occurring in senescent brain. This review describes the link between PKCs and cerebrovascular and cognitive disorders, and proposes PKCs modulators as innovative candidates for their treatment. We report original data showing εPKC reduction in levels and activity in the hippocampus of old compared to young rats and a reduction in the levels of δPKC and γPKC in old hippocampus, without a change in their activity. These data, integrated with other findings discussed in this review, demonstrate that PKCs modulators may have potential to restore age-related reduction of endogenous mechanisms of protection against neurodegeneration.

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Section: Protein Kinase Cs In Brain and Neurological Diseasessupporting

confidence: 82%

Section: Protein Kinase Cs In Brain and Neurological Diseasessupporting

confidence: 72%

Age-Dependent Levels of Protein Kinase Cs in Brain: Reduction of Endogenous Mechanisms of Neuroprotection

Pastore

Pacifici

Dave

et al. 2019

IJMS

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“…Aggregation of toxic β-amyloid (Aβ) oligomers has been recognized as a prominent pathological hallmark for AD, and they are derived from the sequent proteolysis of membrane-bound amyloid precursor protein (APP) by β- and γ- secretases [2]. An increasing amount of evidence has shown that mitochondria is important intracellular organelle for Aβ accumulating [3, 4] and mitochondrial dysfunctions are heavily involved in AD [5]. Nevertheless, the causal link between mitochondrial dysfunction and AD pathogenesis is elusive.…”

Section: Introductionmentioning

confidence: 99%

Studies on APP metabolism related to age-associated mitochondrial dysfunction in APP/PS1 transgenic mice

Chen

et al. 2019

Aging

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The aging brain with mitochondrial dysfunction and a reduced adenosine 5’-triphosphate (ATP) has been implicated in the onset and progression of β-Amyloid (Aβ)-induced neuronal toxicity in AD. To unravel the function of ATP and the underlying mechanisms on AD development, APP/PS1 double transgenic mice and wild-type (WT) C57 mice at 6 and 10 months of age were studied. We demonstrated a decreased ATP release in the hippocampus and platelet of APP/PS1 mice, comparing to C57 mice at a relatively early age. Levels of Aβ were raised in both hippocampus and platelet of APP/PS1 mice, accompanied by a decrease of α-secretase activity and an increase of β-secretase activity. Moreover, our results presented an age-dependent rise in mitochondrial vulnerability to oxidation in APP/PS1 mice. In addition, we found decreased pSer473-Akt levels, increased GSK3β activity by inhibiting phosphorylation at Ser9 in aged APP/PS1 mice and these dysfunctions probably due to down-regulation of Bcl-2 and up-regulation of cleaved caspase-3. Therefore, we demonstrate that PI3K/Akt/GSK3β signaling pathway could be involved in Aβ-associated mitochondrial dysfunction of APP/PS1 mice and APP abnormal metabolism in platelet might provide potential biomarkers for early diagnosis of AD.

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“…Furthermore, the effect of age should be considered. Age-dependent changes have been shown in estrogen signaling in memory-related brain regions (66,67), indicating an age-dependent effect of ovariectomy and estrogen supplementation on cognitive functions in rats (68)(69)(70). On the contrary, there is some evidence indicating that estradiol treatment in young adult (5-month old) and old (24-month old) ovariectomized mice may improve memory in object recognition task in the same manner (71).…”

Section: Discussionmentioning

confidence: 99%

The Role of Estrogen in Anxiety-Like Behavior and Memory of Middle-Aged Female Rats

et al. 2020

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Aging in women is associated with low estrogen, but also with cognitive decline and affective disorders. Whether low estrogen is causally responsible for these behavioral symptoms is not clear. Thus, we aimed to examine the role of estradiol in anxiety-like behavior and memory in rats at middle age. Twelve-month old female rats underwent ovariectomy (OVX) or were treated with 1 mg/kg of letrozole-an aromatase inhibitor. In half of the OVX females, 10 µg/kg of 17β-estradiol was supplemented daily for 4 weeks. Vehicle-treated sham-operated and OVX females served as controls. For behavioral assessment open field, elevated plus maze and novel object recognition tests were performed. Interaction between ovarian condition and additional treatment had the main effect on anxiety-like behavior of rats in the open field test. In comparison to control females, OVX females entered less frequently into the center zone of the open field (p < 0.01) and showed lower novel object discrimination (p = 0.05). However, estradiol-supplemented OVX rats had higher number of center-zone entries (p < 0.01), spent more time in the center zone (p < 0.05), and showed lower thigmotaxis (p < 0.01) when compared to OVX group. None of the hormonal manipulations affected anxiety-like behavior in the elevated plus maze test significantly, but a mild effect of interaction between ovarian condition and treatment was shown (p = 0.05). In conclusion, ovariectomy had slight negative effect on open-field ambulation and short-term recognition memory in middle-aged rats. In addition, a test-specific anxiolytic effect of estradiol supplementation was found. In contrast, letrozole treatment neither affected anxiety-like behavior nor memory.

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Gender- and region-specific changes in estrogen signaling in aging rat brain mitochondria

Cited by 7 publications

References 38 publications

Age-Dependent Levels of Protein Kinase Cs in Brain: Reduction of Endogenous Mechanisms of Neuroprotection

Age-Dependent Levels of Protein Kinase Cs in Brain: Reduction of Endogenous Mechanisms of Neuroprotection

Studies on APP metabolism related to age-associated mitochondrial dysfunction in APP/PS1 transgenic mice

The Role of Estrogen in Anxiety-Like Behavior and Memory of Middle-Aged Female Rats

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