Aging brain

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

Neuroprotective Effect of Dioscin on the Aging Brain.

Abstract: Our previous works have shown that dioscin, a natural product, has various pharmacological activities, however, its role in brain aging has not been reported. In the present study, in vitro H2O2-treated PC12 cells and in vivo d-galactose-induced aging rat models were used to evaluate the neuroprotective effect of dioscin on brain aging. The results showed that dioscin increased cell viability and protected PC12 cells against oxidative stress through decreasing reactive oxygen species (ROS) and lactate dehydrogenase (LDH) levels. In vivo, dioscin markedly improved the spatial learning ability and memory of aging rats, reduced the protein carbonyl content and aging cell numbers, restored the levels of superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px), malondialdehyde (MDA) and nitric oxide synthase (NOS) in brain tissue, and reversed the histopathological structure changes of nerve cells. Mechanism studies showed that dioscin markedly adjusted the MAPK and Nrf2/ARE signalling pathways to decrease oxidative stress. Additionally, dioscin also significantly decreased inflammation by inhibiting the mRNA or protein levels of TNF-α, IL-1β, IL-6, CYP2E1 and HMGB1. Taken together, these results indicate that dioscin showed neuroprotective effect against brain aging via decreasing oxidative stress and inflammation, which should be developed as an efficient candidate in clinical to treat brain aging in the future.

Spermidine, a caloric restriction mimetic, provides neuroprotection against normal and d-galactose-induced oxidative stress and apoptosis through activation of autophagy in male rats during aging

Abstract: Spermidine (SPD) is a natural polyamine present in all living organisms and is involved in the maintenance of cellular homeostasis by inducing autophagy in different model organisms. Its role as a caloric restriction mimetic (CRM) is still being investigated. We have undertaken this study to investigate whether SPD, acting as a CRM, can confer neuroprotection in d-galactose induced accelerated senescence model rat and naturally aged rats through modulation of autophagy and inflammation. Young male rats (4 months), d-gal induced (500 mg/kg b.w., subcutaneously) aging and naturally aged (22 months) male rats were supplemented with SPD (10 mg/kg b.w., orally) for 6 weeks. Standard protocols were employed to measure prooxidants, antioxidants, apoptotic cell death and electron transport chain complexes in brain tissues. Gene expression analysis with reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to assess the expression of autophagy and inflammatory marker genes. Our data demonstrate that SPD significantly (p ≤ 0.05) decreased the level of pro-oxidants and increased the level of antioxidants. SPD supplementation also augmented the activities of electron transport chain complexes in aged brain mitochondria thus proving its antioxidant potential at the level of mitochondria. RT-PCR data revealed that SPD up-regulated the expression of autophagy genes (ATG-3, Beclin-1, ULK-1 and LC3B) and down-regulated the expression of the inflammatory gene (IL-6) in aging brain. Our results provide first line of evidence that SPD provides neuroprotection against aging-induced oxidative stress by regulating autophagy, antioxidants level and also reduces neuroinflammation. These results suggest that SPD may be beneficial for neuroprotection during aging and age-related disorders.

Studies on aging processes.

Abstract: By means of computer assisted morphometry and microdensitometry it has been possible to characterize aging processes in transmitter identified neurons demonstrated at the presynaptic level by immunocytochemistry and at the postsynaptic level by receptor autoradiography. Three-month- and 24-month-old rats were used in the present study. It was discovered that the DA neurons innervating the striatum and nucleus accumbens underwent degeneration in the aging brain both at the pre- and post-synaptic level, while the DA synapses within the tuberculum olfactorium remained intact. In this quantitative receptor autoradiographical analysis 3H-spiperone and 3H-N-propyl-norapomorphine were used as radioligands for DA receptors. In comparison with the aging induced changes in DA receptors in the striatum and in the nucleus accumbens the alpha 2- and the beta-adrenergic receptors appeared to be more resistant to the aging process. In the analysis of the opiate receptors of the aging brain it could be demonstrated by quantitative receptor autoradiography using both radioligands for the mu-type (3H-etorphin) and delta-type (3H-d-ala2-d-leu5-enkephalin) of opiate receptors that there is a marked and widespread disappearance of both types of opiate receptors in the aging brain. It must be emphasized that no correlation exists in the degeneration pattern of the mu- and delta-type of opioid receptors indicating that they may represent two separate entities with separate trophic regulation. In contrast, it was discovered in the quantitative receptor autoradiographical analysis that 3H-flunitrazepam binding was increased in many areas of the aging brain compared with the adult rat brain. These results underline the heterogeneity in the degenerative patterns which take place in transmitter receptors in relation to aging. Thus, these results indicate that the simple replacement therapy in aged patients may not give optimal results. As a matter of fact, such treatments can lead to a further unbalance between the various types of transmitter identified neurons building up the neuronal networks of the brain, which are undergoing degeneration.

Primary Cultures of Rat Cerebellar Granule Cells as a Model to Study Neuronal 5‐Lipoxygenase and FLAP Gene Expression

Abstract: Aging is associated with chronic neurodegenerative diseases and increased brain vulnerability that may lead to a worse outcome from brain insults in elderly than in young subjects. Inflammation is one of the patholphysiological mechanisms of both chronic and acute neurodegeneration. Leukotrienes are inflammatory lipid mediators whose formation from arachidonic acid is initiated by 5-lipoxygenase (5-LO). 5-LO is also expressed in neurons and can be activated by brain injuries, whereas 5-LO inhibitors can provide neuroprotection. The expression of the 5-LO gene appears to be inhibited by the pineal hormone, melatonin, and stimulated by stress hormone glucocorticoids (e.g., corticosterone and the synthetic glucocorticoid dexamethasone). Melatonin deficiency and hyperglucocorticoidemia frequently develop with aging. We found that old or pinealectomized, i.e., melatonin-deficient rats are more susceptible to kainate-triggered excitotoxic limbic brain injury than the corresponding young or sham-pinealectomized controls, and that pinealectomy, aging, or glucocorticoid treatment result in an enhanced expression of 5-LO in limbic structures. We hypothesize that an aging brain is at a higher risk of neurodegeneration via aging-suppressed melatonin secretion and/or aging-increased glucocorticoid secretion and the resultant upregulation of 5-LO expression. Furthermore, we propose that suppressing the 5-LO expression and/or activity will increase the brain's resistance to injury. The results of our ongoing research are expected to elucidate the role of 5-LO in aging and neurodegeneration and to indicate neuroprotective therapies that would target the 5-LO pathway.