Neurochemical Changes in the Aging Process: Implications in Medication in the Elderly

Anyanwu, Ebere C.

doi:10.1100/tsw.2007.112

Cited by 29 publications

(21 citation statements)

References 30 publications

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“…Gonadal steroid hormones and aging have a significant impact on brain neurochemistry and physiology (Anyanwu 2007; Gillies and McArthur 2010). Therefore, we next examined whether the sex difference in GABA B R-dependent signaling was observed in layer 5/6 PrLC pyramidal neurons from young adult (P60–70) mice.…”

Section: Resultsmentioning

confidence: 99%

Sex differences in GABABR-GIRK signaling in layer 5/6 pyramidal neurons of the mouse prelimbic cortex

et al. 2015

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The medial prefrontal cortex (mPFC) has been implicated in multiple disorders characterized by clear sex differences, including schizophrenia, attention deficit hyperactivity disorder, post-traumatic stress disorder, depression, and drug addiction. These sex differences likely represent underlying differences in connectivity and/or the balance of neuronal excitability within the mPFC. Recently, we demonstrated that signaling via the metabotropic γ-aminobutyric acid receptor (GABABR) and G proteingated inwardly-rectifying K+ (GIRK/Kir3) channels modulates the excitability of the key output neurons of the mPFC, the layer 5/6 pyramidal neurons. Here, we report a sex difference in the GABABR-GIRK signaling pathway in these neurons. Specifically, GABABR-dependent GIRK currents recorded in the prelimbic region of the mPFC were larger in adolescent male mice than in female counterparts. Interestingly, this sex difference was not observed in layer 5/6 pyramidal neurons of the adjacent infralimbic cortex, nor was it seen in young adult mice. The sex difference in GABABR-GIRK signaling is not attributable to different expression levels of signaling pathway components, but rather to a phosphorylation-dependent trafficking mechanism. Thus, sex differences related to some diseases associated with altered mPFC function may be explained in part by sex differences in GIRK-dependent signaling in mPFC pyramidal neurons.

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Section: Resultsmentioning

confidence: 99%

Sex differences in GABABR-GIRK signaling in layer 5/6 pyramidal neurons of the mouse prelimbic cortex

et al. 2015

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“…Age is the most important independent risk factor for stroke (Rosamond et al 2008) and the aged brain undergoes numerous neurochemical and physiological changes compared with young brains (Anyanwu 2007). Most experimental stroke studies have been performed on young animals, and therefore may not fully replicate the effects of ischemia on neural tissue in aged subjects.…”

Section: Introductionmentioning

confidence: 99%

Age-related changes in AMP-activated protein kinase after stroke

Liu

Benashski

Persky

et al. 2011

AGE

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Adenosine monophosphate-activated protein kinase (AMPK) is an evolutionary conserved energy sensor sensitive to changes in cellular AMP/ ATP ratio which is activated by phosphorylation (pAMPK). pAMPK levels decrease in peripheral tissues with age, but whether this also occurs in the aged brain, and how this contributes to the ability of the aged brain to cope with ischemic stress is unknown. This study investigated the activation of AMPK and the response to AMPK inhibition after induced stroke in both young and aged male mice. Baseline levels of phosphorylated AMPK were higher in aged brains compared to young mice. Strokeinduced a robust activation of AMPK in young mice, yet this response was muted in the aged brain. Young mice had larger infarct volumes compared with aged animals; however, more severe behavioral deficits and higher mortality were seen in aged mice after stroke. Inhibition of AMPK with Compound C decreased infarct size in young animals, but had no effect in aged mice. Compound C administration led to a reduction in brain ATP levels and induced hypothermia, which led to enhanced neuroprotection in young but not aged mice. This work demonstrates that aging increases baseline brain pAMPK levels; aged mice have a muted stroke-induced pAMPK response; and that AMPK inhibition and hypothermia are less efficacious neuroprotective agents in the aged brain. This has important translational relevance for the development of neuroprotective agents in preclinical models and our understanding of the enhanced metabolic stress experienced by the aged brain.

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“…With increasing life expectancy, elderly patients will soon constitute the majority of stroke victims (Rojas et al, 2007). Numerous neurochemical and physiological changes occur with aging (Anyanwu, 2007) making it critical to model age-related diseases appropriately at the bench. However, aging animals are rarely used in stroke studies due to significant costs of animal care, the increased complexity of surgical procedures, and lower survival rates compared to young animals.…”

Section: Introductionmentioning

confidence: 99%

Expression of Na–K–Cl cotransporter and edema formation are age dependent after ischemic stroke

Akella¹,

Benashski²,

Xu³

et al. 2010

Experimental Neurology

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Age is the most important independent risk factor for stroke; however aging animals are rarely used in stroke studies. Previous work demonstrated that young male mice had more edema formation after an induced stroke than aging animals. An important contributor to cerebral edema formation is the Na-K-Cl cotransporter (NKCC). We examined the expression of NKCC in young (10-12 week) and aging (15-16 months) C57BL6 male mice after middle cerebral artery occlusion (MCAO) and investigated the effect of pharmacological inhibition of NKCC with Bumetanide on cerebral edema formation. Both immunofluorescent staining and Western blotting analysis showed that NKCC expression was significantly higher in the ischemic penumbra of young compared to aging mice after stroke. Edema formation was significantly more robust in young mice and was reduced with Bumetanide. Bumetanide had no effect on cerebral edema in aging mice after MCAO. This suggests that NKCC expression and edema formation are age dependent after ischemic stroke.

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Neurochemical Changes in the Aging Process: Implications in Medication in the Elderly

Cited by 29 publications

References 30 publications

Sex differences in GABABR-GIRK signaling in layer 5/6 pyramidal neurons of the mouse prelimbic cortex

Sex differences in GABABR-GIRK signaling in layer 5/6 pyramidal neurons of the mouse prelimbic cortex

Age-related changes in AMP-activated protein kinase after stroke

Expression of Na–K–Cl cotransporter and edema formation are age dependent after ischemic stroke

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