Aging brain

About: Aging brain is a research topic. Over the lifetime, 1255 publications have been published within this topic receiving 66405 citations.

Neuronal hemoglobin in mitochondria is reduced by forming a complex with α-synuclein in aging monkey brains

Abstract: Neuronal hemoglobin (nHb) plays a critical role in maintaining normal mitochondrial functioning in the brain. However, in aging and Parkinson's disease (PD) brains, mitochondrial nHb levels are greatly reduced in neurons that accumulate α-synuclein (α-syn), suggesting a link between the two proteins. In this study, we demonstrate that α-syn and Hb can form a complex in both brain tissue and peripheral red blood cells (RBCs) in aging cynomolgus monkeys. nHb-α-syn complex levels in the mitochondrial fraction of the striatum decreased with age; this was negatively correlated with levels in the cytoplasmic fraction and in RBCs and was accompanied by a reduction in mitochondrial free nHb. In contrast, no changes in nHb-α-syn complex formation or free nHb levels were detected in the cerebellum. In vitro studies using a cultured dopaminergic cell line showed that intracellular accumulation of α-syn caused an elevation in nHb-α-syn complex levels in both mitochondrial and cytoplasmic fractions as well as a reduction in mitochondrial free nHb. nHb overexpression increased free nHb levels in mitochondria, stabilized mitochondrial membrane potential, and reduced α-syn-induced apoptosis. The above results suggest that α-syn forms a complex with nHb in selected regions of the aging brain, thereby decreasing mitochondrial function and increasing the risk of PD.

The Middle-Aged Brain: Biological sex and sex hormones shape memory circuitry.

Abstract: Over the last quarter century, a staggering number of brain imaging studies have probed the neural basis of age-related cognitive decline. Using multimodal brain imaging tools, we now have a clearer understanding of the morphological, neurochemical, and neurophysiological changes that accompany age-related declines in working memory, selective attention, inhibitory control, episodic memory and more (for review, see Cabeza, Nyberg & Park, 2016). These studies generally target adults over the age of 65, a historical precedent rooted in the average retirement age of U.S. wage-earners. An unintended consequence of this adopted standard is that it overlooks one of the most significant neuroendocrine changes in a woman’s life – the transition to menopause. In turn, it obscures our understanding of sex-dependent pathways that may shape the brain early in the aging process. The median age of menopause is 52.4 years (Gold et al., 2001). The time between the first clinical appearance of decreased ovarian function (i.e. shorter inter-menstrual time periods) to menstrual irregularity and final amenorrhea is variable and protracted, occurring over several years. The menopausal transition is marked by a decline in ovarian hormone production and is a time when many women report changes in memory and attention (e.g. “menopause fog”). Two decades of rodent and nonhuman primate studies have established the role of sex hormones in the synaptic organization of the hippocampus and prefrontal cortex (PFC), and their impact on memory function (Frick et al., 2017, Hara et al. 2015). A parallel literature has emerged within the human cognitive neuroscience field to identify the role of sex hormones in memory circuitry in the human brain. In this review, we summarize recent studies of the neural and cognitive changes that unfold in the middle decade of life (ages 45–60), as a function of sex, reproductive stage, and sex steroid hormones. As the ‘cognitive neuroscience of aging’ field evolves, applying a sex dependent lens to the study of the aging brain will enhance the translation of these findings for both sexes and ensure that men and women get the full benefit of our research efforts. By ignoring the midlife window, we risk missing critical clues that could reveal sex-dependent risk factors of future neurodegenerative disease.

Into the Fourth Dimension: Dysregulation of Genome Architecture in Aging and Alzheimer's Disease.

Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by synapse dysfunction and cognitive impairment. Understanding the development and progression of AD is challenging, as the disease is highly complex and multifactorial. Both environmental and genetic factors play a role in AD pathogenesis, highlighted by observations of complex DNA modifications at the single gene level, and by new evidence that also implicates changes in genome architecture in AD patients. The four-dimensional structure of chromatin in space and time is essential for context-dependent regulation of gene expression in post-mitotic neurons. Dysregulation of epigenetic processes have been observed in the aging brain and in patients with AD, though there is not yet agreement on the impact of these changes on transcription. New evidence shows that proteins involved in genome organization have altered expression and localization in the AD brain, suggesting that the genomic landscape may play a critical role in the development of AD. This review discusses the role of the chromatin organizers and epigenetic modifiers in post-mitotic cells, the aging brain, and in the development and progression of AD. How these new insights can be used to help determine disease risk and inform treatment strategies will also be discussed.

Reciprocal Induction Between α-Synuclein and β-Amyloid in Adult Rat Neurons

Abstract: In spite of definite roles for β-amyloid (Aβ) in familial Alzheimer's disease (AD), the cause of sporadic AD remains unknown Amyloid senile plaques and Lewy body pathology frequently coexist in neocortical and hippocampal regions of AD and Parkinson's diseases However, the relationship between Aβ and α-synuclein (α-Syn), the principle components in the pathological structures, in neuronal toxicity and the mechanisms of their interaction are not well studied As Aβ and α-Syn accumulate in aging patients, the biological functions and toxicity of these polypeptides in the aging brain may be different from those in young brain We examined the neurotoxicity influences of Aβ1-42 or α-Syn on mature neurons and the effects of Aβ1-42 or α-Syn on the production of endogenous α-Syn or Aβ1-40 reciprocally using a model of culture enriched with primary neurons from the hippocampus of adult rats Treatment of neurons with high concentrations of Aβ1-42 or α-Syn caused significant apoptosis of neurons Following Aβ1-42 treatment at sub apoptotic concentrations, both intra- and extra-cellular α-Syn levels were significantly increased Reciprocally, the non-toxic levels of α-Syn treatment also increased intra- and extra-cellular Aβ1-40 levels The phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, suppressed α-Syn-induced Aβ1-40 elevation, as well as Aβ1-42-induced α-Syn elevation Thus, high concentrations of Aβ1-42 and α-Syn exert toxic effects on mature neurons; however, non-toxic concentration treatment of these polypeptides induced the production of each other reciprocally with possible involvement of PI3K pathway