Energy metabolism of rat cerebral cortex, hypothalamus and hypophysis during ageing

Villa, R. F.; Ferrari, Francesca; Gorini, A.

doi:10.1016/j.neuroscience.2012.09.041

Cited by 29 publications

(36 citation statements)

References 70 publications

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“…This observation is in accordance with the concept that, although gross abnormalities of metabolic and neurotransmitter function are unlikely to be compatible with survival even in unimpaired but aged animals, subtle changes may accompany the aging process, with biochemical modifications occurring before the lesion becomes apparent [33,92]. Consequently, (e) age-related changes in brain energy metabolism, sustained by enzymes catalytic activities, should be considered as one of the most relevant factors in physiopathological conditions and influencing responses of selected brain areas to pharmacological treatments, predisposing the cerebral tissue to the responsiveness to noxious stimuli because of changes in energy metabolism.…”

Section: Discussionsupporting

confidence: 91%

“…Age-related changes of assayed enzyme activities support the notion of the existence of different catalytic properties between ''large'' and ''small'' synaptosomes, that may indicate a different (1) metabolic competence, as previously discussed, and (2) a different potential susceptibility of the correspondent subfields to noxious stimuli [33].…”

Section: Synaptosomal Metabolism During Agingsupporting

confidence: 77%

“…In fact, most neurological and psychiatric disorders are associated with regional changes in basal metabolism, as postulated by the ''spare respiratory capacity'' hypothesis [29] and as underlined in some studies and reviews also by us [30][31][32][33][34]. Moreover, acetylcholine and its precursors have an important role counteracting cholinergic deficits typical of age-related neurodegenerative diseases, such as Alzheimer's disease, also controlling proliferation and differentiation of astroglial cells, as widely studied by Bramanti et al [35,36].…”

Section: Introductionmentioning

confidence: 99%

“…enzyme activities, (2) identify potential pathogenic mechanisms, and (3) develop a suitable model to study pharmacological interventions. In fact, during aging, changes in energy-linked enzyme properties not only seem to predispose to some important physiopathological modifications in the in vivo brain [14,33,[37][38][39][40][41], but also may settle tissue responsiveness to drug treatments [30-32, 40, 42-46].…”

Section: Introductionmentioning

confidence: 99%

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Energy Metabolism of Synaptosomes from Different Neuronal Systems of Rat Cerebellum During Aging: A Functional Proteomic Characterization

2014

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Functional proteomics was used to characterize age-related changes in energy metabolism of different neuronal pathways within the cerebellar cortex of Wistar rats aged 2, 6, 12, 18, and 24 months. The "large" synaptosomes, derived from the glutamatergic mossy fibre endings which make synaptic contact with the granule cells of the granular layer, and the "small" synaptosomes, derived from the pre-synaptic terminals of granule cells making synaptic contact with the dendrites of Purkinje cells, were isolated by a combined differential/gradient centrifugation technique. Because most brain disorders are associated with bioenergetic changes, the maximum rate (Vmax) of selected enzymes of glycolysis, Krebs' cycle, glutamate and amino acids metabolism, and acetylcholine catabolism were evaluated. The results show that "large" and "small" synaptosomes possess specific and independent metabolic features. This study represents a reliable model to study in vivo (1) the physiopathological molecular mechanisms of some brain diseases dependent on energy metabolism, (2) the responsiveness to noxious stimuli, and (3) the effects of drugs, discriminating their action sites at subcellular level on specific neuronal pathways.

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Section: Discussionsupporting

confidence: 91%

Section: Synaptosomal Metabolism During Agingsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Energy Metabolism of Synaptosomes from Different Neuronal Systems of Rat Cerebellum During Aging: A Functional Proteomic Characterization

2014

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“…Results confirmed that in both EPS and Pl-OGT mice, hypothalamic mitochondria function was significantly reduced, linking placental OGT again to EPS brain programming. Hypothalamic mitochondrial dysfunction has previously been associated with altered whole-body growth and energy homeostasis, as well as stress-related depressive-like behaviors (33)(34)(35)(36)(37)(38). Therefore, the observed phenotypes in male EPS and Pl-OGT mice (HPA hyperresponsivity and dysregulated energy homeostasis) appear to be, at least in part, the result of mitochondrial dysfunction programmed by a reduction in placental OGT during gestation.…”

Section: Discussionmentioning

confidence: 98%

Targeted placental deletion of OGT recapitulates the prenatal stress phenotype including hypothalamic mitochondrial dysfunction

Howerton

Bale

2014

Proc. Natl. Acad. Sci. U.S.A.

141

130

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Maternal stress is a key risk factor in neurodevelopmental disorders, which often have a sex bias in severity and prevalence. We previously identified O-GlcNAc transferase (OGT) as a placental biomarker in our mouse model of early prenatal stress (EPS), where OGT levels were lower in male compared with female tissue and were further decreased following maternal stress. However, the function of placental OGT in programming the developing brain has not been determined. Therefore, we generated a transgenic mouse with targeted placental disruption of Ogt (Pl-OGT) and examined offspring for recapitulation of the adult EPS phenotype. Pl-OGT hemizygous and EPS male placentas showed similar robust changes in gene expression patterns suggestive of an altered ability to respond to endocrine and inflammatory signals, supporting placental OGT as an important mediator of EPS effects. ChIP-Seq for the O-GlcNAc mark identified the 17 beta hydroxysteroid dehydrogenase-3 (Hsd17b3) locus in male EPS placentas, which correlated with a reduction in Hsd17b3 expression and concordant reduced testosterone conversion. Remarkably, Pl-OGT adult offspring had reduced body weights and elevated hypothalamic-pituitary-adrenal stress axis responsivity, recapitulating phenotypes previously reported for EPS males. Further, hypothalamic microarray gene-set enrichment analyses identified reduced mitochondrial function in both Pl-OGT and EPS males. Cytochrome c oxidase activity assays verified this finding, linking reduced placental OGT with critical brain programming. Together, these studies confirm OGT as in important placental biomarker of maternal stress and demonstrate the profound impact a single placental gene has on longterm metabolic and neurodevelopmental programming that may be related to an increased risk for neurodevelopmental disorders.M aternal stress early in gestation has been identified as a risk factor for neurodevelopmental disorders, including autism spectrum disorders and schizophrenia. Despite strong epidemiological evidence, there remains a lack of specific mechanisms of disease development or predictive biomarkers of disease risk. Examination of the placenta is a promising avenue to find these mechanisms and biomarkers because of features of its biology and accessibility for diagnostic purposes postparturition. The placenta is uniquely positioned at the interface between the maternal and fetal compartments and is rapidly developing during the period of gestation at which maternal stress has been identified to increase disease risk to the offspring (1-5). We previously identified a reduction in O-GlcNAc transferase (OGT), an important O-glycotransferase enzyme that plays a critical role in regulation of gene expression through chromatin remodeling, in male placentas following early prenatal stress (EPS) (4). Placental OGT is basally lower in males due to its X-linkage and escaping of X-inactivation in the placenta and further reduced in our mouse model of EPS. Additionally, we established that a targeted reduction of placen...

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Environmental and Physiological Cues on the Hypothalamus During Aging

Nehlin

2017

Healthy Ageing and Longevity

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Energy metabolism of rat cerebral cortex, hypothalamus and hypophysis during ageing

Cited by 29 publications

References 70 publications

Energy Metabolism of Synaptosomes from Different Neuronal Systems of Rat Cerebellum During Aging: A Functional Proteomic Characterization

Energy Metabolism of Synaptosomes from Different Neuronal Systems of Rat Cerebellum During Aging: A Functional Proteomic Characterization

Targeted placental deletion of OGT recapitulates the prenatal stress phenotype including hypothalamic mitochondrial dysfunction

Environmental and Physiological Cues on the Hypothalamus During Aging

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