Interactive effects of a protein kinase AII inhibitor and testosterone on spatial learning in the Morris water maze

Khorshidahmad, Tina; Tabrizian, Kaveh; Vakilzadeh, Gelareh; Nikbin, Parmida; Moradi, Shima; Hosseini-Sharifabad, Ali; Roghani, Ali; Naghdi, Nasser; Sharifzadeh, Mohammad

doi:10.1016/j.bbr.2011.12.028

Cited by 23 publications

(12 citation statements)

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“…Although testosterone replacement has been prescribed to patients with hypogonadism to improve the quality of life and overall health, including the improvement of cognitive function in men (Donatucci et al 2014) and animal models (Bassil and Morley 2010 ;Cunningham and Toma 2010;Margo and Winn 2006), several studies found that testosterone replacement in the hypogonadal condition has either no effect or adverse effects on cognition in animal models (Emamian et al 2010;Harooni et al 2008;Khorshidahmad et al 2012;Naghdi and Asadollahi 2004) and humans (Kenny et al 2004;Lu et al 2006;Maki et al 2007;Vaughan et al 2007;Wolf et al 2000). In addition, previous studies reported that a high dosage of testosterone could lead to increased cell apoptosis (Cunningham et al 2009), neuronal toxicity (Buletko et al 2012), and impaired learning and decreased memory capability in animal models (Emamian et al 2010;Harooni et al 2008;Naghdi et al 2005;Spritzer et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Testosterone replacement attenuates cognitive decline in testosterone-deprived lean rats, but not in obese rats, by mitigating brain oxidative stress

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Pratchayasakul

et al. 2015

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Testosterone replacement improves metabolic parameters and cognitive function in hypogonadism. However, the effects of testosterone therapy on cognition in obese condition with testosterone deprivation have not been investigated. We hypothesized that testosterone replacement improves cognitive function in testosterone-deprived obese rats by restoring brain insulin sensitivity, brain mitochondrial function, and hippocampal synaptic plasticity. Thirty male Wistar rats had either a bilateral orchiectomy (ORX: O, n = 24) or a sham operation (S, n = 6). ORX rats were further divided into two groups fed with either a normal diet (NDO) or a high-fat diet (HFO) for 12 weeks. Then, ORX rats in each dietary group were divided into two subgroups (n = 6/subgroup) and were given either castor oil or testosterone (2 mg/kg/day, s.c.) for 4 weeks. At the end of this protocol, cognitive function, metabolic parameters, brain insulin sensitivity, hippocampal synaptic plasticity, and brain mitochondrial function were determined. We found that testosterone replacement increased peripheral insulin sensitivity, decreased circulation and brain oxidative stress levels, and attenuated brain mitochondrial ROS production in HFO rats. However, testosterone failed to restore hippocampal synaptic plasticity and cognitive function in HFO rats. In contrast, in NDO rats, testosterone decreased circulation and brain oxidative stress levels, attenuated brain mitochondrial ROS production, and restored hippocampal synaptic plasticity as well as cognitive function. These findings suggest that testosterone replacement improved peripheral insulin sensitivity and decreased oxidative stress levels, but failed to restore hippocampal synaptic plasticity and cognitive function in testosterone-deprived obese rats. However, it provided beneficial effects in reversing cognitive impairment in testosterone-deprived non-obese rats.

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Section: Introductionmentioning

confidence: 99%

Testosterone replacement attenuates cognitive decline in testosterone-deprived lean rats, but not in obese rats, by mitigating brain oxidative stress

Pintana

Pongkan

Pratchayasakul

et al. 2015

AGE

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“…Alternatively, the elevated T levels might reflect a positive relationship between T and spatial learning and memory. It has been demonstrated in mice (Pyter et al, 2006), rats (Sandstrom et al, 2006;Leonard and Winsauer, 2011;Spritzer et al, 2011;McConnell et al, 2012;Hawley et al, 2013), and humans (Janowsky et al, 1994;Postma et al, 2000;Silverman et al, 1999;Cherrier et al, 2001;Burkitt et al, 2007) that baseline T is positively correlated with spatial learning and memory (but see Naghdi et al, 2003;Khorshidahmad et al, 2012). Because translocated snakes were in a completely novel environment, any movements that they made required them to learn new topography and remember where key beneficial habitat features (e.g., rodent burrows and other suitable cover) were located.…”

Section: Discussionmentioning

confidence: 99%

Effects of long distance translocation on corticosterone and testosterone levels in male rattlesnakes

Heiken

Brusch

Gartland

et al. 2016

General and Comparative Endocrinology

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Translocation is an increasingly common conservation tool used to augment declining populations or to remove nuisance animals from areas of human conflict. Studies show that venomous snakes translocated long distances may wander and experience increased mortality. However, potential sub-lethal physiological effects on translocated snakes remain unknown. We conducted an experimental study on free-ranging rattlesnakes to test the hypothesis that long distance translocation is stressful. The glucocorticoid response to translocation was variable among snakes. There was some evidence that translocation may be stressful, as baseline corticosterone levels in most snakes rose following translocation, whereas levels remained consistent in control snakes. Interestingly, testosterone levels rose dramatically following translocation, possibly reflecting effects of interaction with new environmental cues and/or resident snakes, or effects of navigation in a new environment. Corticosterone and testosterone were positively correlated. Our study shows that long distance translocation can affect steroid hormone concentrations in rattlesnakes, a result that should be taken into consideration when managing nuisance snakes or repatriating animals to the wild.

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“…The published data suggest that PKAII inhibition could affect the spatial memory. Nonetheless, when a PKAII inhibitor, like H-89, was co-administered with testosterone, negative correlation in memory process was detected [120] . Furthermore, the role of PKAII in cholinergic gene expression modulation has been studied, which confirms that PKAII acts as an important agent in spatial cognition retention in male rats [121] .…”

Section: Protein Kinasesmentioning

confidence: 99%

The Implication of Androgens in the Presence of Protein Kinase C to Repair Alzheimer’s Disease-Induced Cognitive Dysfunction

Amiri

Azadmanesh

Shasaltaneh

et al. 2020

ibj

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Aging, as a major risk factor of memory deficiency, affects neural signaling pathways in hippocampus. In particular, age-dependent androgens deficiency causes cognitive impairments. Several enzymes like PKC are involved in memory deficiency. Indeed, PKC regulatory process mediates α-secretase activation to cleave APP in β-amyloid cascade and tau proteins phosphorylation mechanism. Androgens and cortisol regulate PKC signaling pathways, affecting the modulation of RACK1. Mitogen-activated protein kinase/ERK signaling pathway depends on CREB activity in hippocampal neurons and is involved in regulatory processes via PKC and androgens. Therefore, testosterone and PKC contribute in the neuronal apoptosis. The present review summarizes the current status of androgens, PKC, and their influence on cognitive learning. Inconsistencies in experimental investigations related to this fundamental correlation are also discussed, with emphasis on the mentioned contributors as the probable potent candidates for learning and memory improvement.

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Interactive effects of a protein kinase AII inhibitor and testosterone on spatial learning in the Morris water maze

Cited by 23 publications

References 50 publications

Testosterone replacement attenuates cognitive decline in testosterone-deprived lean rats, but not in obese rats, by mitigating brain oxidative stress

Testosterone replacement attenuates cognitive decline in testosterone-deprived lean rats, but not in obese rats, by mitigating brain oxidative stress

Effects of long distance translocation on corticosterone and testosterone levels in male rattlesnakes

The Implication of Androgens in the Presence of Protein Kinase C to Repair Alzheimer’s Disease-Induced Cognitive Dysfunction

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