Thermoregulatory profile of neurodegeneration‐induced dementia of the Alzheimer's type using intracerebroventricular streptozotocin in rats

Motzko-Soares, Anna Carolina Parracho; Vizin, Robson Cristiano Lillo; Martins, T. M. S.; Hungaro, A. R. O.; Sato, João Ricardo; Almeida, Maria Camila; Carrettiero, Daniel Carneiro

doi:10.1111/apha.13084

Cited by 9 publications

(5 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Each animal received two icv bilateral injections of 2 μL (1 μL/min): the first one was citrate (vehicle) or AEA (100 ng) ( Fraga et al, 2009 ), followed by another injection of vehicle or STZ (2 mg/kg) ( Motzko-Soares et al, 2018 ) 5 min later. After each infusion, the injection needle remained for at least 2 min in place, in order to prevent reflux of the administered solution.…”

Section: Methodsmentioning

confidence: 99%

Anandamide Effects in a Streptozotocin-Induced Alzheimer’s Disease-Like Sporadic Dementia in Rats

et al. 2018

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is characterized by multiple cognitive deficits including memory and sensorimotor gating impairments as a result of neuronal and synaptic loss. The endocannabinoid system plays an important role in these deficits but little is known about its influence on the molecular mechanism regarding phosphorylated tau (p-tau) protein accumulation – one of the hallmarks of AD –, and on the density of synaptic proteins. Thus, the aim of this study was to investigate the preventive effects of anandamide (N-arachidonoylethanolamine, AEA) on multiple cognitive deficits and on the levels of synaptic proteins (syntaxin 1, synaptophysin and synaptosomal-associated protein, SNAP-25), cannabinoid receptor type 1 (CB1) and molecules related to p-tau degradation machinery (heat shock protein 70, HSP70), and Bcl2-associated athanogene (BAG2) in an AD-like sporadic dementia model in rats using intracerebroventricular (icv) injection of streptozotocin (STZ). Our hypothesis is that AEA could interact with HSP70, modulating the level of p-tau and synaptic proteins, preventing STZ-induced cognitive impairments. Thirty days after receiving bilateral icv injections of AEA or STZ or both, the cognitive performance of adult male Wistar rats was evaluated in the object recognition test, by the escape latency in the elevated plus maze (EPM), by the tone and context fear conditioning as well as in prepulse inhibition tests. Subsequently, the animals were euthanized and their brains were removed for histological analysis or for protein quantification by Western Blotting. The behavioral results showed that STZ impaired recognition, plus maze and tone fear memories but did not affect contextual fear memory and prepulse inhibition. Moreover, AEA prevented recognition and non-associative emotional memory impairments induced by STZ, but did not influence tone fear conditioning. STZ increased the brain ventricular area and this enlargement was prevented by AEA. Additionally, STZ reduced the levels of p-tau (Ser199/202) and increased p-tau (Ser396), although AEA did not affect these alterations. HSP70 was found diminished only by STZ, while BAG2 levels were decreased by STZ and AEA. Synaptophysin, syntaxin and CB1 receptor levels were reduced by STZ, but only syntaxin was recovered by AEA. Altogether, albeit AEA failed to modify some AD-like neurochemical alterations, it partially prevented STZ-induced cognitive impairments, changes in synaptic markers and ventricle enlargement. This study showed, for the first time, that the administration of an endocannabinoid can prevent AD-like effects induced by STZ, boosting further investigations about the modulation of endocannabinoid levels as a therapeutic approach for AD.

show abstract

Section: Methodsmentioning

confidence: 99%

Anandamide Effects in a Streptozotocin-Induced Alzheimer’s Disease-Like Sporadic Dementia in Rats

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Thermoregulatory dysfunction was also investigated in animal models of AD (Vandal et al 2016, Motzko-Soares et al 2018.…”

mentioning

confidence: 99%

Autonomic impairment in Alzheimer’s disease is revealed by complexity analysis of functional thermal imaging signals during cognitive tasks

Perpetuini¹,

Cardone

Chiarelli

et al. 2019

Physiol. Meas.

View full text Add to dashboard Cite

Alzheimer's disease (AD) is a dementing disorder that mainly impacts on the memory ability of patients (Dubois et al 2007). Many tests assessing memory deficits have been validated, allowing for a clinical diagnosis of this form of dementia (Cummings et al 2013). Moreover, because of central nervous system (CNS) degeneration, AD can also be characterized by subtle autonomic dysfunctions (Algotsson et al 1995, Affoo et al 2013, Femminella et al 2014. In fact, some studies have reported pathological changes in the autonomous nervous system (ANS) in AD. For instance, experimental tests that assess autonomic functions, such as the Valsalva maneuver and Tilt test, were performed on AD patients and healthy controls (HCs) with heart-rate and pulse amplitude monitoring to study disease-related changes in the parasympathetic, vasomotor and sudomotor sympathetic functions (Algotsson et al 1995). During these tests, AD patients exhibited slower heart rate and reduction in pulse amplitude, suggesting a hypo-sympathetic activity of AD patients with respect to HCs.Other studies have investigated the effect of ANS dysfunction on thermoregulatory activity in AD. A relationship between the progression of cold-intolerance and the course of the disease was found, highlighting both pathophysiological changes and adaptive behavior (Diamond and Diamond 1991). This result suggests that this symptom is not simply a manifestation of cognitive decline regarding neural mechanisms involved in autonomic

show abstract

“…Regarding the behavioral study, the Barnes maze test was utilized to assess differences in spatial learning and memory between the groups. Neurodegeneration was induced by intracerebroventricular STZ injection, leading to a pathology resembling AD [23,24,[42][43][44][45]. Other studies that evaluated the cognitive improvement action of HT in animals used daily gavage of HT acetate 50 mg/kg for 12 weeks [46] or 5 mg/kg/day for six months [47].…”

Section: Discussionmentioning

confidence: 99%

“…Researchers frequently employ the intracerebroventricular injection (icv) of the drug streptozotocin (STZ) to simulate AD in vivo models [23]. This drug (recommended for use only in male rats) is believed to initiate the AD disease cascade by reducing glucose utilization in the brain, leading to metabolic and behavioral disorders and a decrease in ATP and phosphocreatine concentrations [24].…”

Section: Introductionmentioning

confidence: 99%

The Impact of Hydroxytyrosol on the Metallomic-Profile in an Animal Model of Alzheimer’s Disease

Tabanez,

Santos,

Ikebara

et al. 2023

IJMS

View full text Add to dashboard Cite

It is undeniable that as people get older, they become progressively more susceptible to neurodegenerative illnesses such as Alzheimer’s disease (AD). Memory loss is a prominent symptom of this condition and can be exacerbated by uneven levels of certain metals. This study used inductively coupled plasma mass spectrometry (ICP-MS) to examine the levels of metals in the blood plasma, frontal cortex, and hippocampus of Wistar rats with AD induced by streptozotocin (STZ). It also tested the effects of the antioxidant hydroxytyrosol (HT) on metal levels. The Barnes maze behavior test was used, and the STZ group showed less certainty and greater distance when exploring the Barnes maze than the control group. The results also indicated that the control group and the STZ + HT group exhibited enhanced learning curves during the Barnes maze training as compared to the STZ group. The ICP-MS analysis showed that the STZ group had lower levels of cobalt in their blood plasma than the control group, while the calcium levels in the frontal cortex of the STZ + HT group were higher than in the control group. The most important finding was that copper levels in the frontal cortex from STZ-treated animals were higher than in the control group, and that the STZ + HT group returned to equivalent levels to the control group. The antioxidant HT can restore copper levels to their basal physiological state. This finding may help explain HT’s potential beneficial effect in AD-patients.

show abstract

Thermoregulatory profile of neurodegeneration‐induced dementia of the Alzheimer's type using intracerebroventricular streptozotocin in rats

Cited by 9 publications

References 84 publications

Anandamide Effects in a Streptozotocin-Induced Alzheimer’s Disease-Like Sporadic Dementia in Rats

Anandamide Effects in a Streptozotocin-Induced Alzheimer’s Disease-Like Sporadic Dementia in Rats

Autonomic impairment in Alzheimer’s disease is revealed by complexity analysis of functional thermal imaging signals during cognitive tasks

The Impact of Hydroxytyrosol on the Metallomic-Profile in an Animal Model of Alzheimer’s Disease

Contact Info

Product

Resources

About