L-type calcium channel blockade alleviates molecular and reversal spatial learning and memory alterations induced by entorhinal amyloid pathology in rats

Gholamipour-Badie, Hamid; Naderi, Nima; Khodagholi, Fariba; Shaerzadeh, Fatemeh; Motamedi, Fereshteh

doi:10.1016/j.bbr.2012.09.045

Cited by 35 publications

(33 citation statements)

References 66 publications

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“…Most published work supports an action of CCBs on amyloid. In rats, impairment of spatial memory following intracerebroventricular injection of Aβ was prevented both by nilvadipine and nimodipine treatments [76,77]. In a thorough study, Paris et al showed that chronic oral treatment with nilvadipine decreased Aβ burden in the brains of transgenic PS1/APPsw mice, and improved learning abilities and spatial memory [78].…”

Section: Preclinical Studiesmentioning

confidence: 99%

Antihypertensive agents in Alzheimer’s disease: beyond vascular protection

Lebouvier

Chen

Duriez

et al. 2019

Expert Review of Neurotherapeutics

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Introduction: Midlife hypertension has been consistently linked with increased risk of cognitive decline and Alzheimer's disease (AD). Observational studies and randomized trials show that the use of antihypertensive therapy is associated with a lesser incidence or prevalence of cognitive impairment and dementia. However, whether antihypertensive agents specifically target the pathological process of AD remains elusive. Areas covered: This review of literature provides an update on the clinical and preclinical arguments supporting anti-AD properties of antihypertensive drugs. The authors focused on validated all classes of antihypertensive treatments such as angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), calcium channel blockers (CCB), β-blockers, diuretics, neprilysin inhibitors, and other agents. Three main mechanisms can be advocated: action on the concurrent vascular pathology, action on the vascular component of Alzheimer's pathophysiology, and action on nonvascular targets. Expert opinion: In 2019, while there is no doubt that hypertension should be treated in primary prevention of vascular disease and in secondary prevention of stroke and mixed dementia, the place of antihypertensive agents in the secondary prevention of 'pure' AD remains an outstanding question. ARTICLE HISTORY

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Section: Preclinical Studiesmentioning

confidence: 99%

Antihypertensive agents in Alzheimer’s disease: beyond vascular protection

Lebouvier

Chen

Duriez

et al. 2019

Expert Review of Neurotherapeutics

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“…On the other hand, Palop et al found that Aβ elicits aberrant excitatory activity in cortical-hippocampal networks and compensatory responses that are particularly evident in the DG [ 28 ]. In the previous work, we found that isradipine and nimodipine could improve spatial learning and memory deficit induced by microinjection of Aβ into the EC [ 29 ]. It is believed that dysfunction of the perforant pathway projection from the EC to the DG is an important contributor to the onset and progression of cognitive impairment in AD [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Preventing Effect of L-Type Calcium Channel Blockade on Electrophysiological Alterations in Dentate Gyrus Granule Cells Induced by Entorhinal Amyloid Pathology

et al. 2015

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The entorhinal cortex (EC) is one of the earliest affected brain regions in Alzheimer’s disease (AD). EC-amyloid pathology induces synaptic failure in the dentate gyrus (DG) with resultant behavioral impairment, but there is little known about its impact on neuronal properties in the DG. It is believed that calcium dyshomeostasis plays a pivotal role in the etiology of AD. Here, the effect of the EC amyloid pathogenesis on cellular properties of DG granule cells and also possible neuroprotective role of L-type calcium channel blockers (CCBs), nimodipine and isradipine, were investigated. The amyloid beta (Aβ) 1–42 was injected bilaterally into the EC of male rats and one week later, electrophysiological properties of DG granule cells were assessed. Voltage clamp recording revealed appearance of giant sIPSC in combination with a decrease in sEPSC frequency which was partially reversed by CCBs in granule cells from Aβ treated rats. EC amyloid pathogenesis induced a significant reduction of input resistance (Rin) accompanied by a profound decreased excitability in the DG granule cells. However, daily administration of CCBs, isradipine or nimodipine (i.c.v. for 6 days), almost preserved the normal excitability against Aβ. In conclusion, lower tendency to fire AP along with reduced Rin suggest that DG granule cells might undergo an alteration in the membrane ion channel activities which finally lead to the behavioral deficits observed in animal models and patients with early-stage Alzheimer’s disease.

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“…Treatment of diabetic animals with nimodipine was shown to be effective in reducing the calpain and caspase‐3 expression to control levels. Enhanced calpain and caspase‐3 activity observed in AD rats was also found to be attenuated following supplementation of L‐type CCB (nimodipine/isradipine; Gholamipour‐Badie et al, ). Choudhary and Gill () also suggested that the nimodipine‐induced ameliorative effect could be attributed to its inhibitory action on elevated [Ca 2+ ] i .…”

Section: Discussionmentioning

confidence: 96%

L‐type calcium channel blocker ameliorates diabetic encephalopathy by modulating dysregulated calcium homeostasis

Singhal

Sandhir

2014

J of Neuroscience Research

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Diabetic encephalopathy is a complication of diabetes characterized by impaired cognitive functions. The objective of the present study was to examine the beneficial effect of the calcium channel blocker, nimodipine, on diabetes-induced cognitive deficits and altered calcium homeostasis in the cerebral cortex. Diabetes was induced in mice by intraperitoneal injection of streptozotocin (40 mg/kg body wt) for 5 days. Nimodipine (10 mg/kg body weight) was administered intraperitoneally to the animals every 48 hr for 8 weeks. A significant impairment in spatial learning and memory was observed in diabetic animals, which was reversed by nimodipine treatment. Diabetic animals showed increased CaV1.2 mRNA and protein expression, which might be responsible for enhanced synaptosomal calcium uptake. Nimodipine treatment was found to lower CaV1.2 mRNA, protein expression, and calcium uptake. Mitochondrial Ca(2+) uptake was reduced in diabetic brains, which was reversed with nimodipine treatment. Plasma membrane and sarcoplasmic reticulum Ca(2+) -ATPase activity was found to be significantly decreased in diabetic animals, whereas nimodipine supplementation restored the activity of both Ca(2+) -ATPases nearly to control values. Nimodipine treatment was shown to normalize intracellular free Ca(2+) levels in diabetic animals. Nimodipine was shown to attenuate increased calpain activity measured in terms of hydrolysis of fluorogenic substrate and αII-spectrin degradation. Nimodipine supplementation also reduced reactive oxygen species production and lipid peroxidation in diabetic animals. The data suggests that L-type calcium channel blocker is beneficial in preventing cognitive deficits associated with diabetic encephalopathy through modulation of dysregulated calcium homeostasis.

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L-type calcium channel blockade alleviates molecular and reversal spatial learning and memory alterations induced by entorhinal amyloid pathology in rats

Cited by 35 publications

References 66 publications

Antihypertensive agents in Alzheimer’s disease: beyond vascular protection

Antihypertensive agents in Alzheimer’s disease: beyond vascular protection

Preventing Effect of L-Type Calcium Channel Blockade on Electrophysiological Alterations in Dentate Gyrus Granule Cells Induced by Entorhinal Amyloid Pathology

L‐type calcium channel blocker ameliorates diabetic encephalopathy by modulating dysregulated calcium homeostasis

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