scholarly journals Increased Endogenous GDNF in Mice Protects Against Age-Related Decline in Neuronal Cholinergic Markers

2021 ◽  
Vol 13 ◽  
Author(s):  
Sumonto Mitra ◽  
Giorgio Turconi ◽  
Taher Darreh-Shori ◽  
Kärt Mätlik ◽  
Matilde Aquilino ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Cholinergic Neurons ◽  
Lewy Body Dementia ◽  
Cholinergic Transmission ◽  
Expression Of Genes ◽  
Age Related ◽  
Y Maze ◽  
In The Wild ◽  
And Function ◽  
Cholinergic Markers

Gradual decline in cholinergic transmission and cognitive function occurs during normal aging, whereas pathological loss of cholinergic function is a hallmark of different types of dementia, including Alzheimer’s disease (AD), Lewy body dementia (LBD), and Parkinson’s disease dementia (PDD). Glial cell line-derived neurotrophic factor (GDNF) is known to modulate and enhance the dopamine system. However, how endogenous GDNF influences brain cholinergic transmission has remained elusive. In this study, we explored the effect of a twofold increase in endogenous GDNF (Gdnf hypermorphic mice, Gdnfwt/hyper) on cholinergic markers and cognitive function upon aging. We found that Gdnfwt/hyper mice resisted an overall age-associated decline in the cholinergic index observed in the brain of Gdnfwt/wt animals. Biochemical analysis revealed that the level of nerve growth factor (NGF), which is important for survival and function of central cholinergic neurons, was significantly increased in several brain areas of old Gdnfwt/hyper mice. Analysis of expression of genes involved in cholinergic transmission in the cortex and striatum confirmed modulation of cholinergic pathways by GDNF upon aging. In line with these findings, Gdnfwt/hyper mice did not undergo an age-related decline in cognitive function in the Y-maze test, as observed in the wild type littermates. Our results identify endogenous GDNF as a potential modulator of cholinergic transmission and call for future studies on endogenous GDNF function in neurodegenerative disorders characterized by cognitive impairments, including AD, LBD, and PDD.

scholarly journals Cholinergic Degeneration and Alterations in the TrkA and p75NTR Balance as a Result of Pro-NGF Injection into Aged Rats

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Ashley M. Fortress ◽  
Mona Buhusi ◽  
Kris L. Helke ◽  
Ann-Charlotte E. Granholm
Keyword(s):  
Basal Forebrain ◽  
Cholinergic Neurons ◽  
Memory Impairments ◽  
Age Related ◽  
High Affinity Receptor ◽  
Affinity Receptor ◽  
Cholinergic Degeneration ◽  
And Function ◽  
Do So

Learning and memory impairments occurring with Alzheimer's disease (AD) are associated with degeneration of the basal forebrain cholinergic neurons (BFCNs). BFCNs extend their axons to the hippocampus where they bind nerve growth factor (NGF) which is retrogradely transported to the cell body. While NGF is necessary for BFCN survival and function via binding to the high-affinity receptor TrkA, its uncleaved precursor, pro-NGF has been proposed to induce neurodegeneration via binding to the p75NTR and its coreceptor sortilin. Basal forebrain TrkA and NGF are downregulated with aging while pro-NGF is increased. Given these data, the focus of this paper was to determine a mechanism for how pro-NGF accumulation may induce BFCN degeneration. Twenty-four hours after a single injection of pro-NGF into hippocampus, we found increased hippocampal p75NTR levels, decreased hippocampal TrkA levels, and cholinergic degeneration. The data suggest that the increase in p75NTR with AD may be mediated by elevated pro-NGF levels as a result of decreased cleavage, and that pro-NGF may be partially responsible for age-related degenerative changes observed in the basal forebrain. This paper is the firstin vivoevidence that pro-NGF can affect BFCNs and may do so by regulating expression of p75NTR neurotrophin receptors.

The Application of the Rorschach Inkblot Test in the Study of Neural and Cognitive Aging

2020 ◽  
Vol 41 (1) ◽  
pp. 1-18 ◽  
Author(s):  
Eamonn Arble ◽  
Steven W. Steinert ◽  
Ana M. Daugherty
Keyword(s):  
Cognitive Function ◽  
Cognitive Aging ◽  
Mirror Neuron ◽  
Present Review ◽  
Age Related ◽  
Brain Structure And Function ◽  
Rorschach Inkblot Test ◽  
Cortical Regions ◽  
Inkblot Test ◽  
And Function

Abstract. The Rorschach Inkblot test has been adopted and adapted by many researchers to assess and predict different aspects of human experience and cognitive performance. The present review examines research that incorporates the Rorschach to evaluate neural and cognitive aging as well as decline in age-related disease. Specifically, differences in amygdala and cortical regions, as well as mirror neuron and asymmetrical hemisphere activity that correlate with specific responses to Rorschach stimuli are discussed in the context of typical changes in brain structure and function in the course of aging. In addition, the present review provides a proposed framework for expanding the use of the Rorschach to evaluate other domains of neural and cognitive function. The authors conclude that, despite a need for increased research, the Rorschach is a viable measure to evaluate certain aspects of cognitive function and decline throughout the lifespan.

scholarly journals Dietary Polyphenols as Modulators of Brain Functions: Biological Actions and Molecular Mechanisms Underpinning Their Beneficial Effects

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
David Vauzour
Keyword(s):  
Cognitive Function ◽  
Molecular Mechanisms ◽  
Inflammatory Stress ◽  
Dietary Polyphenols ◽  
Beneficial Effects ◽  
Brain Functions ◽  
Expression Of Genes ◽  
Age Related ◽  
Neuroprotective Actions ◽  
Protective Signaling

Accumulating evidence suggests that diet and lifestyle can play an important role in delaying the onset or halting the progression of age-related health disorders and to improve cognitive function. In particular, polyphenols have been reported to exert their neuroprotective actions through the potential to protect neurons against injury induced by neurotoxins, an ability to suppress neuroinflammation, and the potential to promote memory, learning, and cognitive function. Despite significant advances in our understanding of the biology of polyphenols, they are still mistakenly regarded as simply acting as antioxidants. However, recent evidence suggests that their beneficial effects involve decreases in oxidative/inflammatory stress signaling, increases in protective signaling and neurohormetic effects leading to the expression of genes that encode antioxidant enzymes, phase-2 enzymes, neurotrophic factors, and cytoprotective proteins. Specific examples of such pathways include the sirtuin-FoxO pathway, the NF-κB pathway, and the Nrf-2/ARE pathway. Together, these processes act to maintain brain homeostasis and play important roles in neuronal stress adaptation and thus polyphenols have the potential to prevent the progression of neurodegenerative pathologies.

scholarly journals Triple nanoemulsion potentiates the effects of topical treatments with microencapsulated retinol and modulates biological processes related to skin aging

2013 ◽  
Vol 88 (6) ◽  
pp. 930-936 ◽  
Author(s):  
Alessandro Afornali ◽  
Rodrigo de Vecchi ◽  
Rodrigo Makowiecky Stuart ◽  
Gustavo Dieamant ◽  
Luciana Lima de Oliveira ◽  
...  
Keyword(s):  
Genetic Factors ◽  
Biological Process ◽  
Ex Vivo ◽  
Skin Aging ◽  
Biological Processes ◽  
Skin Damage ◽  
Expression Of Genes ◽  
Age Related ◽  
Reverse Transcription Quantitative Pcr ◽  
And Function

BACKGROUND: The sum of environmental and genetic factors affects the appearance and function of the skin as it ages. The identification of molecular changes that take place during skin aging provides biomarkers and possible targets for therapeutic intervention. Retinoic acid in different formulations has emerged as an alternative to prevent and repair age-related skin damage. OBJECTIVES: To understand the effects of different retinoid formulations on the expression of genes associated with biological processes that undergo changes during skin aging. METHODS: Ex-vivo skin samples were treated topically with different retinoid formulations. The modulation of biological processes associated with skin aging was measured by Reverse Transcription quantitative PCR (RT-qPCR). RESULTS: A formulation containing microencapsulated retinol and a blend of active ingredients prepared as a triple nanoemulsion provided the best results for the modulation of biological, process-related genes that are usually affected during skin aging. CONCLUSION: This association proved to be therapeutically more effective than tretinoin or microencapsulated retinol used singly.

scholarly journals γ-Oryzanol Improves Cognitive Function and Modulates Hippocampal Proteome in Mice

Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 753 ◽  
Author(s):  
Wiramon Rungratanawanich ◽  
Giovanna Cenini ◽  
Andrea Mastinu ◽  
Marc Sylvester ◽  
Anne Wilkening ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Brain Function ◽  
Clinical Symptoms ◽  
Oryza Sativa L ◽  
Beneficial Effects ◽  
Adult Mice ◽  
Age Related ◽  
Y Maze ◽  
Quantitative Changes

Rice (Oryza sativa L.) is the richest source of γ-oryzanol, a compound endowed with antioxidant and anti-inflammatory properties. γ-Oryzanol has been demonstrated to cross the blood-brain barrier in intact form and exert beneficial effects on brain function. This study aimed to clarify the effects of γ-oryzanol in the hippocampus in terms of cognitive function and protein expression. Adult mice were administered with γ-oryzanol 100 mg/kg or vehicle (control) once a day for 21 consecutive days following which cognitive behavior and hippocampal proteome were investigated. Cognitive tests using novel object recognition and Y-maze showed that long-term consumption of γ-oryzanol improves cognitive function in mice. To investigate the hippocampal proteome modulated by γ-oryzanol, 2D-difference gel electrophoresis (2D-DIGE) was performed. Interestingly, we found that γ-oryzanol modulates quantitative changes of proteins involved in synaptic plasticity and neuronal trafficking, neuroprotection and antioxidant activity, and mitochondria and energy metabolism. These findings suggested γ-oryzanol as a natural compound able to maintain and reinforce brain function. Although more intensive studies are needed, we propose γ-oryzanol as a putative dietary phytochemical for preserving brain reserve, the ability to tolerate age-related changes, thereby preventing clinical symptoms or signs of neurodegenerative diseases.

scholarly journals Adropin correlates with aging-related neuropathology in humans and improves cognitive function in aging mice

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Subhashis Banerjee ◽  
Sarbani Ghoshal ◽  
Clemence Girardet ◽  
Kelly M. DeMars ◽  
Changjun Yang ◽  
...  
Keyword(s):  
Cellular Metabolism ◽  
Enrichment Analysis ◽  
Spatial Learning And Memory ◽  
Oligodendrocyte Progenitor Cells ◽  
Protein Markers ◽  
Markers Of Inflammation ◽  
Expression Of Genes ◽  
Age Related ◽  
And Function ◽  
Mrna Markers

AbstractThe neural functions of adropin, a secreted peptide highly expressed in the brain, have not been investigated. In humans, adropin is highly expressed in astrocytes and peaks during critical postnatal periods of brain development. Gene enrichment analysis of transcripts correlating with adropin expression suggests processes relevant to aging-related neurodegenerative diseases that vary with age and dementia state, possibly indicating survivor bias. In people aged <40 y and ‘old-old’ (>75 y) diagnosed with dementia, adropin correlates positively with genes involved in mitochondrial processes. In the ‘old-old’ without dementia adropin expression correlates positively with morphogenesis and synapse function. Potent neurotrophic responses in primary cultured neurons are consistent with adropin supporting the development and function of neural networks. Adropin expression in the ‘old-old’ also correlates positively with protein markers of tau-related neuropathologies and inflammation, particularly in those without dementia. How variation in brain adropin expression affects neurological aging was investigated using old (18-month) C57BL/6J mice. In mice adropin is expressed in neurons, oligodendrocyte progenitor cells, oligodendrocytes, and microglia and shows correlative relationships with groups of genes involved in neurodegeneration and cellular metabolism. Increasing adropin expression using transgenesis improved spatial learning and memory, novel object recognition, resilience to exposure to new environments, and reduced mRNA markers of inflammation in old mice. Treatment with synthetic adropin peptide also reversed age-related declines in cognitive functions and affected expression of genes involved in morphogenesis and cellular metabolism. Collectively, these results establish a link between adropin expression and neural energy metabolism and indicate a potential therapy against neurological aging.

scholarly journals Exogenous NGF Affects Cholinergic Transmitter Function and Y-Maze Behavior in Aged Fischer 344 Male Rats

1991 ◽  
Vol 18 (S3) ◽  
pp. 403-407 ◽  
Author(s):  
Lawrence R. Williams ◽  
R. Jane Rylett ◽  
Hylan C. Moises ◽  
Andrew H. Tang
Keyword(s):  
Brightness Discrimination ◽  
Cholinergic Neurons ◽  
Male Rats ◽  
Neuronal Markers ◽  
Fischer 344 ◽  
Cognitive Measure ◽  
Age Related ◽  
Y Maze ◽  
Cholinergic Phenotype ◽  
The Brain

ABSTRACT:Chronic ICV administration of NGF stimulates the activity of the cholinergic neuronal markers, HACU and ChAT, as well as the evoked release of both endogenous and newly synthesized acetylcholine in the brain of aging Fischer 344 male rats. However, the pattern of cholinergic phenotype stimulation indicates an age-related differential regulation of ChAT, HACU, and ACh release between specific brain areas, with the largest.effects found in the striatum. NGF treatment also increases the effectiveness of neurotransmission between basal forebrain cholinergic neurons and postsynaptic amygdaloid target neurons. The stimulation of central cholinergic transmitter function after NGF treatment affects behavior in a Y-maze brightness discrimination paradigm. NGF treatment does not affect the cognitive measure of brightness discrimination, but reduces the number of avoidance attempts, a measure of motor function.

scholarly journals Adropin expression correlates with aging-related neuropathology in the human brain and improves neuroinflammation and cognitive function in aging mice

2021 ◽  
Author(s):  
Subhashis Banerjee ◽  
Sarbani Ghoshal ◽  
Clemence Girardet ◽  
Kelly M. DeMars ◽  
Changjun Yang ◽  
...  
Keyword(s):  
Cellular Metabolism ◽  
Enrichment Analysis ◽  
Spatial Learning And Memory ◽  
Oligodendrocyte Progenitor Cells ◽  
Protein Markers ◽  
Novel Therapy ◽  
Markers Of Inflammation ◽  
Expression Of Genes ◽  
Age Related ◽  
And Function

Abstract The neural functions of adropin, a secreted peptide highly expressed in the brain, have not been investigated. In humans, adropin is highly expressed in astrocytes and peaks during critical postnatal periods of brain development. Gene enrichment analysis of transcripts correlating with adropin expression suggests processes relevance to aging-related neurodegenerative diseases that vary with age and dementia state, possibly indicating survivor bias. In people aged <40y and ‘oldold’ (>75y) diagnosed with dementia, adropin correlates positively with genes involved in mitochondrial processes. In the ‘old-old’ without dementia adropin expression correlates positively with morphogenesis and synapse function. Potent neurotrophic responses in primary cultured neurons are consistent with adropin supporting the development and function of neural networks. Adropin expression in the ‘old-old’ also correlates positively with protein markers of tau-related neuropathologies and inflammation, particularly in those without dementia. How variation in brain adropin expression affects neurological aging was investigated using old (18- month) C57BL/6J mice. In mice adropin is expressed in neurons, oligodendrocyte progenitor cells, oligodendrocytes, and microglia and shows correlative relationships with groups of genes involved in neurodegeneration and cellular metabolism. Increasing adropin expression using transgenesis improved spatial learning and memory, novel object recognition, resilience to exposure to new environments, and reduced mRNA markers of inflammation in old mice. Treatment with synthetic adropin peptide also reversed age-related declines of cognitive functions and affected expression of genes involved in morphogenesis and cellular metabolism. Collectively, these results establish a link between adropin expression and neural energy metabolism and indicate a potential novel therapy against neurological aging.

scholarly journals Treadmill Exercise During Cerebral Hypoperfusion Has Only Limited Effects on Cognitive Function in Middle-Aged Subcortical Ischemic Vascular Dementia Mice

2021 ◽  
Vol 13 ◽  
Author(s):  
Ryo Ohtomo ◽  
Hidehiro Ishikawa ◽  
Keita Kinoshita ◽  
Kelly K. Chung ◽  
Gen Hamanaka ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Vascular Dementia ◽  
Treadmill Exercise ◽  
Basic Research ◽  
Cerebrovascular Diseases ◽  
Cerebral Hypoperfusion ◽  
Middle Aged ◽  
Age Related ◽  
Y Maze ◽  
Aging Populations

Clinical and basic research suggests that exercise is a safe behavioral intervention and is effective for improving cognitive function in cerebrovascular diseases, including subcortical ischemic vascular dementia (SIVD). However, most of the basic research uses young animals to assess the effects of exercise, although SIVD is an age-related disease. In this study, therefore, we used middle-aged mice to examine how treadmill exercise changes the cognitive function of SIVD mice. As a mouse model of SIVD, prolonged cerebral hypoperfusion was induced in 8-month-old male C57BL/6J mice by bilateral common carotid artery stenosis. A week later, the mice were randomly divided into two groups: a group that received 6-week treadmill exercise and a sedentary group for observation. After subjecting the mice to multiple behavioral tests (Y-maze, novel object recognition, and Morris water maze tests), the treadmill exercise training was shown to only be effective in ameliorating cognitive decline in the Y-maze test. We previously demonstrated that the same regimen of treadmill exercise was effective in young hypoperfused-SIVD mice for all three cognitive tests. Therefore, our study may indicate that treadmill exercise during cerebral hypoperfusion has only limited effects on cognitive function in aging populations.

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