Aging brain

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

Is Dendritic Proliferation of Surviving Neurons a Compensatory Response to Loss of Neighbors in the Aging Brain

Abstract: The plastic capacities of the developing brain are well known, and it is the young brain that usually is emphasized when considering neuronal plasticity. The view taken here is that the plastic capacity of the developing brain does not suddenly cease as some developmental landmark is reached but that some degree of residual plasticity is maintained to the end of the developmental continuum (death). Functionally, this residual plasticity may be manifested in a variety of ways, including (1) recovery from strokes and lesions and (2) compensatory responses to the degenerative phenomena of the aging brain. We define neuronal “plasticity” as the adaptive response(s) of neurons to perturbations in their local environment. The perturbations may be in the chemical composition of the neuron’s immediate surround, its afferent supply, its targets, or in its neighboring neurons and glia. The plastic response(s) to such perturbations may include alteration in dendritic and/or axonal morphology, in synapses, receptors, metabolism, even in genetic expression (e.g., Black et al., 1984: Davis et al., 1986).

Brain cytochrome oxidase activity of synaptic and nonsynaptic mitochondria during aging.

Abstract: The activity of cytochrome c oxidase was studied in aging brain on non-synaptic and intra-synaptic mitochondria from frontal cerebral cortex, hippocampus and striatum of 4, 8, 12, 16, 20 and 24 month-old Sprague-Dawley rats. Specific activities of cytochrome oxidase were significantly higher in light synaptic mitochondria than in non-synaptic or heavy ones at all the ages examined. However, enzyme activity in light mitochondria from cerebral cortex remains unchanged during aging, being increased in hippocampus and striatum. These results indicate that aging affected not only the various cerebral area (macroheterogeneity), but also the different mitochondrial populations (subcellular heterogeneity).

Delayed and Blunted Induction of mRNA for Tissue Plasminogen Activator in the Brain of Old Rats Following Pentylenetetrazole-Induced Seizure Activity

Abstract: The ability of the rodent brain to support plasticity-related phenomena declines with increasing age. Here we investigated the extent to which old rats retain the capacity to initiate transcription for immediate early genes, particularly as it relates to brain plasticity, in response to a strong stimulus. The intraperitoneal administration of pentylenetetrazole (PTZ) to rats of various ages evoked tonic-clonic seizures. Using an RNA gel-blot and in situ hybridization analysis, we found that 1 hour after the onset of seizure, messenger RNA (mRNA) for tissue plasminogen activator (TPA) was increased approximately 3.7-fold in the hippocampi of 3-month-old rats. The levels of TPA mRNA in the hippocampi and cortices of 3-month-old rats returned to control levels by 3 hours after PTZ administration. The levels of TPA mRNA increased 2.5-fold in the hippocampi of 18-month-old rats and 1.8-fold in the brains of the 28-month-old-rats at 3 hours and returned to basal levels by 15 hours following PTZ treatment. Quantitatively similar increases were calculated for the cortex. At peak induction the transcripts were localized throughout the cortical layers of the 3-month-old rats, whereas the TPA mRNA expression was restricted to cortical layer V of the older rats. Our results suggest that although the aging brain retains the capacity to respond to chemically induced seizures, the induction of TPA mRNA is temporarily delayed and the levels are diminished with increasing age. Because TPA has been implicated in neuronal plasticity, this finding suggests that immediate early genes are important factors in the limited plasticity of the aging brain.

Endothelial Nitric Oxide Synthase-Deficient Mice

Abstract: Age-related cerebral small-vessel disease (CSVD) is a major cause of stroke and dementia. Despite a widespread acceptance of small-vessel arteriopathy, lacunar infarction, diffuse white matter injury, and cognitive impairment as four cardinal features of CSVD, a unifying pathologic mechanism of CSVD remains elusive. Herein, we introduce partial endothelial nitric oxide synthase (eNOS)-deficient mice as a model of age-dependent, spontaneous CSVD. These mice developed cerebral hypoperfusion and blood-brain barrier leakage at a young age, which progressively worsened with advanced age. Their brains exhibited elevated oxidative stress, astrogliosis, cerebral amyloid angiopathy, microbleeds, microinfarction, and white matter pathology. Partial eNOS-deficient mice developed gait disturbances at middle age, and hippocampus-dependent memory deficits at older ages. These mice also showed enhanced expression of bone morphogenetic protein 4 (BMP4) in brain pericytes before myelin loss and white matter pathology. Because BMP4 signaling not only promotes astrogliogenesis but also blocks oligodendrocyte differentiation, we posit that paracrine actions of BMP4, localized within the neurovascular unit, promote white matter disorganization and neurodegeneration. These observations point to BMP4 signaling pathway in the aging brain vasculature as a potential therapeutic target. Finally, because studies in partial eNOS-deficient mice corroborated recent clinical evidence that blood-brain barrier disruption is a primary cause of white matter pathology, the mechanism of impaired nitric oxide signaling-mediated CSVD warrants further investigation.

Age-Related Alterations in Brain Perfusion, Venous Oxygenation, and Oxygen Metabolic Rate of Mice: A 17-Month Longitudinal MRI Study.

Abstract: Background: Characterization of physiological parameters of the aging brain, such as perfusion and brain metabolism, is important for understanding brain function and diseases. Aging studies on human brain have mostly been based on the cross-sectional design, while the few longitudinal studies used relatively short follow-up time compared to the lifespan. Objectives: To determine the longitudinal time courses of cerebral physiological parameters across the adult lifespan in mice. Methods: The present work examined longitudinal changes in cerebral blood flow (CBF), cerebral venous oxygenation (Yv), and cerebral metabolic rate of oxygen (CMRO2) using MRI in healthy C57BL/6 mice from 3 to 20 months of age. Each mouse received 16 imaging sessions at an ~1-month interval. Results: Significant increases with age were observed in CBF (p = 0.017) and CMRO2 (p < 0.001). Meanwhile, Yv revealed a significant decrease (p = 0.002) with a non-linear pattern (p = 0.013). The rate of change was 0.87, 2.26, and -0.24% per month for CBF, CMRO2, and Yv, respectively. On the other hand, systemic parameters such as heart rate did not show a significant age dependence (p = 0.47). No white-matter-hyperintensities (WMH) were observed on the T2-weighted image at any age of the mice. Conclusion: With age, the mouse brain revealed an increase in oxygen consumption. This observation is consistent with previous findings in humans using a cross-sectional design and suggests a degradation of the brain's energy production or utilization machinery. Cerebral perfusion remains relatively intact in aged mice, at least until 20 months of age, consistent with the absence of WMH in mice.