scholarly journals Contributions of the Brain Angiotensin IV–AT4Receptor Subtype System to Spatial Learning

1999 ◽  
Vol 19 (10) ◽  
pp. 3952-3961 ◽  
Author(s):  
John W. Wright ◽  
LeighAnn Stubley ◽  
Eric S. Pederson ◽  
Enikö A. Kramár ◽  
Jodi M. Hanesworth ◽  
...  
Keyword(s):  
Spatial Learning ◽  
Angiotensin Iv ◽  
The Brain

scholarly journals Reappearance of Hippocampal CA1 Neurons after Ischemia is Associated with Recovery of Learning and Memory

2005 ◽  
Vol 25 (12) ◽  
pp. 1586-1595 ◽  
Author(s):  
Olof Bendel ◽  
Tjerk Bueters ◽  
Mia von Euler ◽  
Sven Ove Ögren ◽  
Johan Sandin ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Cognitive Functions ◽  
Spatial Learning And Memory ◽  
Neuronal Marker ◽  
Ca1 Neurons ◽  
Ca1 Region ◽  
Hippocampal Ca1 ◽  
The Brain

The pyramidal neurons of the hippocampal CA1 region are essential for cognitive functions such as spatial learning and memory, and are selectively destroyed after cerebral ischemia. To analyze whether degenerated CA1 neurons are replaced by new neurons and whether such regeneration is associated with amelioration in learning and memory deficits, we have used a rat global ischemia model that provides an almost complete disappearance (to approximately 3% of control) of CA1 neurons associated with a robust impairment in spatial learning and memory at two weeks after ischemia. We found that transient cerebral ischemia can evoke a massive formation of new neurons in the CA1 region, reaching approximately 40% of the original number of neurons at 90 days after ischemia (DAI). Co-localization of the mature neuronal marker neuronal nuclei with 5-bromo-2'-deoxyuridine in CA1 confirmed that neurogenesis indeed had occurred after the ischemic insult. Furthermore, we found increased numbers of cells expressing the immature neuron marker polysialic acid neuronal cell adhesion molecule in the adjacent lateral periventricular region, suggesting that the newly formed neurons derive from this region. The reappearance of CA1 neurons was associated with a recovery of ischemia-induced impairments in spatial learning and memory at 90 DAI, suggesting that the newly formed CA1 neurons restore hippocampal CA1 function. In conclusion, these results show that the brain has an endogenous capacity to form new nerve cells after injury, which correlates with a restoration of cognitive functions of the brain.

scholarly journals Disparate Central and Peripheral Effects of Circulating IGF-1 Deficiency on Tissue Mitochondrial Function

2019 ◽  
Vol 57 (3) ◽  
pp. 1317-1331 ◽  
Author(s):  
Gavin Pharaoh ◽  
Daniel Owen ◽  
Alexander Yeganeh ◽  
Pavithra Premkumar ◽  
Julie Farley ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cognitive Function ◽  
Spatial Learning ◽  
Mitochondrial Function ◽  
Coupling Efficiency ◽  
Redox Status ◽  
Cellular Aging ◽  
Age Related ◽  
The Brain ◽  
Circulating Levels

AbstractAge-related decline in circulating levels of insulin-like growth factor (IGF)-1 is associated with reduced cognitive function, neuronal aging, and neurodegeneration. Decreased mitochondrial function along with increased reactive oxygen species (ROS) and accumulation of damaged macromolecules are hallmarks of cellular aging. Based on numerous studies indicating pleiotropic effects of IGF-1 during aging, we compared the central and peripheral effects of circulating IGF-1 deficiency on tissue mitochondrial function using an inducible liver IGF-1 knockout (LID). Circulating levels of IGF-1 (~ 75%) were depleted in adult male Igf1f/f mice via AAV-mediated knockdown of hepatic IGF-1 at 5 months of age. Cognitive function was evaluated at 18 months using the radial arm water maze and glucose and insulin tolerance assessed. Mitochondrial function was analyzed in hippocampus, muscle, and visceral fat tissues using high-resolution respirometry O2K as well as redox status and oxidative stress in the cortex. Peripherally, IGF-1 deficiency did not significantly impact muscle mass or mitochondrial function. Aged LID mice were insulin resistant and exhibited ~ 60% less adipose tissue but increased fat mitochondrial respiration (20%). The effects on fat metabolism were attributed to increases in growth hormone. Centrally, IGF-1 deficiency impaired hippocampal-dependent spatial acquisition as well as reversal learning in male mice. Hippocampal mitochondrial OXPHOS coupling efficiency and cortex ATP levels (~ 50%) were decreased and hippocampal oxidative stress (protein carbonylation and F2-isoprostanes) was increased. These data suggest that IGF-1 is critical for regulating mitochondrial function, redox status, and spatial learning in the central nervous system but has limited impact on peripheral (liver and muscle) metabolism with age. Therefore, IGF-1 deficiency with age may increase sensitivity to damage in the brain and propensity for cognitive deficits. Targeting mitochondrial function in the brain may be an avenue for therapy of age-related impairment of cognitive function. Regulation of mitochondrial function and redox status by IGF-1 is essential to maintain brain function and coordinate hippocampal-dependent spatial learning. While a decline in IGF-1 in the periphery may be beneficial to avert cancer progression, diminished central IGF-1 signaling may mediate, in part, age-related cognitive dysfunction and cognitive pathologies potentially by decreasing mitochondrial function.

scholarly journals The role of dietary niacin intake and the adenosine-5′-diphosphate-ribosyl cyclase enzyme CD38 in spatial learning ability: is cyclic adenosine diphosphate ribose the link between diet and behaviour?

2008 ◽  
Vol 21 (1) ◽  
pp. 42-55 ◽  
Author(s):  
Genevieve S. Young ◽  
James B. Kirkland
Keyword(s):  
Spatial Learning ◽  
Young Male ◽  
Adenosine Diphosphate ◽  
Pyridine Nucleotide ◽  
Learning Ability ◽  
Learning Performance ◽  
Male Rats ◽  
Current Evidence ◽  
Niacin Deficiency ◽  
The Brain

The pyridine nucleotide NAD+is derived from dietary niacin and serves as the substrate for the synthesis of cyclic ADP-ribose (cADPR), an intracellular Ca signalling molecule that plays an important role in synaptic plasticity in the hippocampus, a region of the brain involved in spatial learning. cADPR is formed in part via the activity of the ADP-ribosyl cyclase enzyme CD38, which is widespread throughout the brain. In the present review, current evidence of the relationship between dietary niacin and behaviour is presented following investigations of the effect of niacin deficiency, pharmacological nicotinamide supplementation and CD38 gene deletion on brain nucleotides and spatial learning ability in mice and rats. In young male rats, both niacin deficiency and nicotinamide supplementation significantly altered brain NAD+and cADPR, both of which were inversely correlated with spatial learning ability. These results were consistent across three different models of niacin deficiency (pair feeding, partially restricted feeding and niacin recovery). Similar changes in spatial learning ability were observed inCd38− / − mice, which also showed decreases in brain cADPR. These findings suggest an inverse relationship between spatial learning ability, dietary niacin intake and cADPR, although a direct link between cADPR and spatial learning ability is still missing. Dietary niacin may therefore play a role in the molecular events regulating learning performance, and further investigations of niacin intake, CD38 and cADPR may help identify potential molecular targets for clinical intervention to enhance learning and prevent or reverse cognitive decline.

Elevated Seizure Threshold and Impaired Spatial Learning in Transgenic Mice with Putrescine Overproduction in the Brain

1993 ◽  
Vol 5 (9) ◽  
pp. 1233-1239 ◽  
Author(s):  
T. Halonen ◽  
J. Sivenius ◽  
R. Miettinen ◽  
M. Halmekytö ◽  
R. Kauppinen ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Spatial Learning ◽  
Seizure Threshold ◽  
The Brain

scholarly journals 27-Hydroxycholesterol impairs neuronal glucose uptake through an IRAP/GLUT4 system dysregulation

2017 ◽  
Vol 214 (3) ◽  
pp. 699-717 ◽  
Author(s):  
Muhammad-Al-Mustafa Ismail ◽  
Laura Mateos ◽  
Silvia Maioli ◽  
Paula Merino-Serrais ◽  
Zeina Ali ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Renin Angiotensin System ◽  
Angiotensin Iv ◽  
Memory Decline ◽  
Brain Glucose ◽  
Glut4 Expression ◽  
Altered Glucose ◽  
X Receptors ◽  
The Brain

Hypercholesterolemia is associated with cognitively deteriorated states. Here, we show that excess 27-hydroxycholesterol (27-OH), a cholesterol metabolite passing from the circulation into the brain, reduced in vivo brain glucose uptake, GLUT4 expression, and spatial memory. Furthermore, patients exhibiting higher 27-OH levels had reduced 18F-fluorodeoxyglucose uptake. This interplay between 27-OH and glucose uptake revealed the engagement of the insulin-regulated aminopeptidase (IRAP). 27-OH increased the levels and activity of IRAP, countered the IRAP antagonist angiotensin IV (AngIV)–mediated glucose uptake, and enhanced the levels of the AngIV-degrading enzyme aminopeptidase N (AP-N). These effects were mediated by liver X receptors. Our results reveal a molecular link between cholesterol, brain glucose, and the brain renin-angiotensin system, all of which are affected in some neurodegenerative diseases. Thus, reducing 27-OH levels or inhibiting AP-N maybe a useful strategy in the prevention of the altered glucose metabolism and memory decline in these disorders.

Prandial increase of leptin in the brain activates spatial learning and memory

2010 ◽  
Vol 17 (2) ◽  
pp. 119-127 ◽  
Author(s):  
Yutaka Oomura ◽  
Shuji Aou ◽  
Kouji Fukunaga
Keyword(s):  
Learning And Memory ◽  
Spatial Learning ◽  
Spatial Learning And Memory ◽  
The Brain

scholarly journals Angiotensin IV suppresses inflammation in the brains of rats with chronic cerebral hypoperfusion

2018 ◽  
Vol 19 (3) ◽  
pp. 147032031879958 ◽  
Author(s):  
Qing-Guang Wang ◽  
Xiao Xue ◽  
Yang Yang ◽  
Peng-Yu Gong ◽  
Teng Jiang ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Neurological Diseases ◽  
Amyloid Β ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Angiotensin Iv ◽  
Artificial Cerebrospinal Fluid ◽  
Ang Iv ◽  
The Brain ◽  
Pro Inflammatory Cytokines

Introduction: This study aimed to evaluate the influence of central angiotensin IV (Ang IV) infusion on chronic cerebral hypoperfusion (CCH)-related neuropathological changes including amyloid-β (Aβ), hyperphosphorylated tau (p-tau) and the inflammatory response. Materials and methods: Rats with CCH received central infusion of Ang IV, its receptor AT4R antagonist divalinal-Ang IV or artificial cerebrospinal fluid for six weeks. During this procedure, the systolic blood pressure (SBP) was monitored, and the levels of Aβ42, p-tau and pro-inflammatory cytokines in the brain were detected. Results: Rats with CCH exhibited higher levels of Aβ42, p-tau and pro-inflammatory cytokines in the brain when compared with controls. Infusion of Ang IV significantly reduced the expression of pro-inflammatory cytokines in the brains of rats with CCH. Meanwhile, the reduction of pro-inflammatory cytokines levels caused by Ang IV was reversed by divalinal-Ang IV. During the treatment, the SBP in rats was not significantly altered. Conclusion: This study demonstrates for the first time that Ang IV dose-dependently suppresses inflammation through AT4R in the brains of rats with CCH, which is independent from SBP. These findings suggest that Ang IV/AT4R may represent a potential therapeutic target for CCH-related neurological diseases.

Effect of GDNF on depressive-like behavior, spatial learning and key genes of the brain dopamine system in genetically predisposed to behavioral disorders mouse strains

2014 ◽  
Vol 274 ◽  
pp. 1-9 ◽  
Author(s):  
Vladimir S. Naumenko ◽  
Elena M. Kondaurova ◽  
Daria V. Bazovkina ◽  
Anton S. Tsybko ◽  
Tatyana V. Ilchibaeva ◽  
...  
Keyword(s):  
Behavioral Disorders ◽  
Spatial Learning ◽  
Mouse Strains ◽  
Brain Dopamine ◽  
Dopamine System ◽  
Key Genes ◽  
The Brain

scholarly journals Discovery of Inhibitors of Insulin-Regulated Aminopeptidase as Cognitive Enhancers

2012 ◽  
Vol 2012 ◽  
pp. 1-18 ◽  
Author(s):  
Hanna Andersson ◽  
Mathias Hallberg
Keyword(s):  
Intracerebroventricular Injection ◽  
Binding Affinities ◽  
Ang Ii ◽  
Angiotensin Iv ◽  
Positive Effects ◽  
Main Target ◽  
The Status ◽  
Ang Iv ◽  
The Relationship ◽  
The Brain

The hexapeptide angiotensin IV (Ang IV) is a metabolite of angiotensin II (Ang II) and plays a central role in the brain. It was reported more than two decades ago that intracerebroventricular injection of Ang IV improved memory and learning in the rat. Several hypotheses have been put forward to explain the positive effects of Ang IV and related analogues on cognition. It has been proposed that the insulin-regulated aminopeptidase (IRAP) is the main target of Ang IV. This paper discusses progress in the discovery of inhibitors of IRAP as potential enhancers of cognitive functions. Very potent inhibitors of the protease have been synthesised, but pharmacokinetic issues (including problems associated with crossing the blood-brain barrier) remain to be solved. The paper also briefly presents an overview of the status in the discovery of inhibitors of ACE and renin, and of AT1R antagonists and AT2R agonists, in order to enable other discovery processes within the RAS system to be compared. The paper focuses on the relationship between binding affinities/inhibition capacity and the structures of the ligands that interact with the target proteins.

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