Flupirtine attenuates chronic restraint stress-induced cognitive deficits and hippocampal apoptosis in male mice.

Abstract:

:Chronic restraint stress (CRS) causes hippocampal neurodegeneration and hippocampus-dependent cognitive deficits. Flupirtine represents neuroprotective effects and we have previously shown that flupirtine can protect against memory impairment induced by acute stress. The present study aimed to investigate whether flupirtine could alleviate spatial learning and memory impairment and hippocampal apoptosis induced by CRS. CRS mice were restrained in well-ventilated Plexiglass tubes for 6h daily beginning from 10:00 to 16:00 for 21 consecutive days. Mice were injected with flupirtine (10mg/kg and 25mg/kg) or vehicle (10% DMSO) 30min before restraint stress for 21 days. After stressor cessation, the spatial learning and memory, dendritic spine density, injured neurons and the levels of Bcl-2, Bax, p-Akt, p-GSK-3β, p-Erk1/2 and synaptophysin of hippocampal tissues were examined. Our results showed that flupirtine significantly prevented spatial learning and memory impairment induced by CRS in the Morris water maze. In addition, flupirtine (10mg/kg and 25mg/kg) treatment alleviated neuronal apoptosis and the reduction of dendritic spine density and synaptophysin expression in the hippocampal CA1 region of CRS mice. Furthermore, flupirtine (10mg/kg and 25mg/kg) treatment significantly decreased the expression of Bax and increased the p-Akt and p-GSK-3β, and flupirtine (25mg/kg) treatment up-regulated the p-Erk1/2 in the hippocampus of CRS mice. These results suggested that flupirtine exerted protective effects on the CRS-induced cognitive impairment and hippocampal neuronal apoptosis, which is possibly associated with the activation of Akt/GSK-3β and Erk1/2 signaling pathways.

journal_name

Behav Brain Res

authors

Huang P,Li C,Fu T,Zhao D,Yi Z,Lu Q,Guo L,Xu X

doi

10.1016/j.bbr.2015.04.004

subject

Has Abstract

pub_date

2015-07-15 00:00:00

pages

1-10

eissn

0166-4328

issn

1872-7549

pii

S0166-4328(15)00246-6

journal_volume

288

pub_type

杂志文章
  • Prepulse inhibition of acoustic startle in spontaneously hypertensive rats.

    abstract::Prepulse inhibition is modulated by dopaminergic drugs and is disrupted in attention-deficit hyperactivity disorder, as well as mental illnesses such as schizophrenia. Spontaneously hypertensive rats (SHR) have been proposed as an animal model of attention-deficit hyperactivity disorder and show marked alterations of ...

    journal_title:Behavioural brain research

    pub_type: 杂志文章

    doi:10.1016/j.bbr.2004.02.021

    authors: van den Buuse M

    更新日期:2004-10-05 00:00:00

  • Earlier is not always better: behavioral dysfunction and abnormal cerebral morphogenesis following neonatal cortical lesions in the rat.

    abstract::Rats with lesions of the medial frontal, ventral frontal or posterior parietal cortex in adulthood were compared behaviorally and neuroanatomically in adulthood with rats with similar removals at 7 days of age. The neonatal lesions altered cortical morphogenesis, especially in the ventral frontal and parietal groups, ...

    journal_title:Behavioural brain research

    pub_type: 杂志文章

    doi:10.1016/0166-4328(85)90005-1

    authors: Kolb B,Whishaw IQ

    更新日期:1985-09-01 00:00:00

  • The effects of chronic mild stress on male Sprague-Dawley and Long Evans rats: I. Biochemical and physiological analyses.

    abstract::The chronic unpredictable mild stress (CMS) is a paradigm developed in animals to model the relatively minor and unanticipated irritants that lead to a state of anhedonia in some individuals. However, the effectiveness of CMS is sometimes difficult to establish, for which unique strain sensitivities has been attribute...

    journal_title:Behavioural brain research

    pub_type: 杂志文章

    doi:10.1016/s0166-4328(02)00222-x

    authors: Bielajew C,Konkle AT,Merali Z

    更新日期:2002-11-15 00:00:00

  • Lateral neglect in a head movement task: more impairment with unilateral than bilateral lesions of the superior colliculus in the rat.

    abstract::Unilateral lesions of the superior colliculus produce contralateral neglect. This study determined if bilateral lesions would impair head orientation in a way expected from the summation of two contralateral neglects. Rats were trained to make various head movements to get water at a 3 x 3 array of holes, each with a ...

    journal_title:Behavioural brain research

    pub_type: 杂志文章

    doi:10.1016/0166-4328(88)90039-3

    authors: Sinnamon HM,Garcia EJ

    更新日期:1988-02-01 00:00:00

  • Behavioral characteristics of rats predisposed to learned helplessness: reduced reward sensitivity, increased novelty seeking, and persistent fear memories.

    abstract::The congenitally helpless rat strain, which was selectively bred for increased susceptibility to learned helplessness, may model the predisposition to affective disorders, including depression and post-traumatic stress disorder. Other than the selected trait, the behavior of this strain is not well characterized. In t...

    journal_title:Behavioural brain research

    pub_type: 杂志文章

    doi:10.1016/j.bbr.2005.06.016

    authors: Shumake J,Barrett D,Gonzalez-Lima F

    更新日期:2005-11-07 00:00:00

  • Zebrafish (Danio rerio) responds differentially to stimulus fish: the effects of sympatric and allopatric predators and harmless fish.

    abstract::The zebrafish has been an excellent model organism of developmental biology and genetics. Studying its behavior will add to the already strong knowledge of its biology and will strengthen the use of this species in behavior genetics and neuroscience. Anxiety is one of the most problematic human psychiatric conditions....

    journal_title:Behavioural brain research

    pub_type: 杂志文章

    doi:10.1016/j.bbr.2007.07.037

    authors: Bass SL,Gerlai R

    更新日期:2008-01-10 00:00:00

  • Brain sites mediating the discriminative stimulus effects of nicotine in rats.

    abstract::Pharmacological studies suggest that the discriminative stimulus (DS) produced by nicotine is mediated centrally. The aim of the present study was to identify neuroanatomical substrates that mediate the DS properties of nicotine. Specifically, the nucleus accumbens, a brain region known to mediate the DS effects of am...

    journal_title:Behavioural brain research

    pub_type: 杂志文章

    doi:10.1016/0166-4328(95)00245-6

    authors: Shoaib M,Stolerman IP

    更新日期:1996-08-01 00:00:00

  • Effect of local 6-OHDA and 5,6-DHT injections into the rat olfactory bulb on neophobia and learned aversion to a novel food.

    abstract::This study investigated the role of the noradrenergic (NA) and the serotoninergic (5-HT) centrifugal fibers on the olfactory bulb (OB). For this purpose, behavioral responses largely depending on olfactory information were measured in rats after discrete bilateral injections into the OB with either 6-hydroxydopamine (...

    journal_title:Behavioural brain research

    pub_type: 杂志文章

    doi:10.1016/0166-4328(83)90036-0

    authors: Royet JP,Gervais R,Araneda S

    更新日期:1983-12-01 00:00:00

  • Hippocampal BDNF treatment facilitates consolidation of spatial memory in spontaneous place recognition in rats.

    abstract::In order to investigate the role of brain-derived neurotrophic factor (BDNF) in the consolidation of spatial memory, we examined the relationship between the increase of hippocampal BDNF and the establishment of long-term spatial memory in spontaneous place recognition test in rats. The test consisted of a sample phas...

    journal_title:Behavioural brain research

    pub_type: 杂志文章

    doi:10.1016/j.bbr.2014.01.034

    authors: Ozawa T,Yamada K,Ichitani Y

    更新日期:2014-04-15 00:00:00

  • Genetic dissection of nicotine-related behaviour: a review of animal studies.

    abstract::Nicotine has a broad spectrum of behavioural effects. A considerable body of data has emerged indicating genetic factors regulate the behavioural effects of nicotine. Experimental genetic techniques have been invaluable in generating knowledge on the interrelationship of genetic factors and behavioural responsiveness ...

    journal_title:Behavioural brain research

    pub_type: 杂志文章,评审

    doi:10.1016/s0166-4328(00)00198-4

    authors: Mohammed AH

    更新日期:2000-08-01 00:00:00

  • Membrane potential and input resistance of cat spinal motoneurons in wakefulness and sleep.

    abstract::An approximation of the membrane resistance - input resistance - was measured with double-barrelled micropipettes in hindlimb motoneurons during wakefulness and the states of sleep in chronically implanted, restrained cats. During postural atonia in rapid-eye-movement (REM) sleep, motoneurons had a sustained hyperpola...

    journal_title:Behavioural brain research

    pub_type: 杂志文章

    doi:10.1016/0166-4328(81)90060-7

    authors: Glenn LL,Dement WC

    更新日期:1981-03-01 00:00:00

  • Perirhinal cortex lesions that impair object recognition memory spare landmark discriminations.

    abstract::Rats with lesions in the perirhinal cortex and their control group learnt to discriminate between mirror-imaged visual landmarks to find a submerged platform in a watermaze. Rats initially learnt this discrimination passively, in that they were repeatedly placed on the platform in one corner of a square watermaze with...

    journal_title:Behavioural brain research

    pub_type: 杂志文章

    doi:10.1016/j.bbr.2016.07.031

    authors: Nelson AJD,Olarte-Sánchez CM,Amin E,Aggleton JP

    更新日期:2016-10-15 00:00:00

  • The nucleus accumbens in monkeys (Macaca fascicularis): I. The organization of behaviour.

    abstract::A behavioural comparison was made between six unoperated control monkeys and six monkeys which received bilateral ibotenic acid lesions of the nucleus accumbens. Two of the control monkeys were subsequently given bilateral lesions of the anterior cingulate and medial frontal cortex (areas 24, 25 and 32) and were retes...

    journal_title:Behavioural brain research

    pub_type: 杂志文章

    doi:10.1016/0166-4328(94)90003-5

    authors: Stern CE,Passingham RE

    更新日期:1994-03-31 00:00:00

  • Sex differences and reversal of brain asymmetry by testosterone in chickens.

    abstract::The study examined the effect of testosterone on the asymmetry of visual discrimination performance of young chicks. Two-week-old chicks were tested on the pebble floor visual discrimination task. Male chicks were found to have brain asymmetry for visual discrimination learning, since chicks tested binocularly, or tes...

    journal_title:Behavioural brain research

    pub_type: 杂志文章

    doi:10.1016/0166-4328(87)90026-x

    authors: Zappia JV,Rogers LJ

    更新日期:1987-03-01 00:00:00

  • Amygdalar activation of group I metabotropic glutamate receptors produces anti- and pro-conflict effects depending upon animal sex in a sexually dimorphic conditioned conflict-based anxiety model.

    abstract::Women are more susceptible than men to develop anxiety disorders, however, the mechanisms involved are still unclear. In this study, we investigated the role of group I metabotropic glutamate receptors (mGluRs), a target for anxiety disorders, and whether estradiol may modulate conflict-based anxiety in female rats by...

    journal_title:Behavioural brain research

    pub_type: 杂志文章

    doi:10.1016/j.bbr.2016.01.009

    authors: De Jesús-Burgos MI,González-García S,Cruz-Santa Y,Pérez-Acevedo NL

    更新日期:2016-04-01 00:00:00

  • Bizarre behaviors and risk assessment in 3xTg-AD mice at early stages of the disease.

    abstract::Bizarre behaviors (stereotyped stretching, stereotyped rearing, backward movements and jumps) were conspicuously elicited in classical unconditioned tests with different levels of anxiogenic conditions. They were characterized for the first time as early-BPSD-like symptoms in 6 month-old male and female 3xTg-AD mice. ...

    journal_title:Behavioural brain research

    pub_type: 杂志文章

    doi:10.1016/j.bbr.2013.10.017

    authors: Baeta-Corral R,Giménez-Llort L

    更新日期:2014-01-01 00:00:00

  • Sexually dimorphic behavioral and neural responses to a predator scent.

    abstract::Male and female C57BL/6 J mice were tested on the predator odor response task, where they needed to cross through a chamber of scented bedding to reach a sucrose reward. Following the behavioral testing, mouse brains were immunohistochemically labeled for expression of the immediate early gene c-fos. In the presence o...

    journal_title:Behavioural brain research

    pub_type: 杂志文章

    doi:10.1016/j.bbr.2020.112467

    authors: Francesconi JA,Macaroy C,Sawant S,Hamrick H,Wahab S,Klein I,McGann JP

    更新日期:2020-03-16 00:00:00

  • Neural mechanisms underlying the changes in ipsilateral primary motor cortex excitability during unilateral rhythmic muscle contraction.

    abstract::The aim of this study was to investigate the neural mechanisms underlying the changes in the ipsilateral primary motor cortex (ipsi-M1) excitability induced during the unilateral rhythmic muscle contraction of the first dorsal interosseous (FDI) (rhythmic contraction) muscle with three different frequencies of auditor...

    journal_title:Behavioural brain research

    pub_type: 杂志文章

    doi:10.1016/j.bbr.2012.10.053

    authors: Uehara K,Morishita T,Kubota S,Funase K

    更新日期:2013-03-01 00:00:00

  • Validation of a 2-day water maze protocol in mice.

    abstract::We present a 2-day water maze protocol that addresses some of potential confounds present in the water maze when using the aged subjects typical of studies of neurodegenerative disorders, such as Alzheimer's disease. This protocol is based on an initial series of training trials with a visible platform, followed by a ...

    journal_title:Behavioural brain research

    pub_type: 杂志文章

    doi:10.1016/j.bbr.2008.09.002

    authors: Gulinello M,Gertner M,Mendoza G,Schoenfeld BP,Oddo S,LaFerla F,Choi CH,McBride SM,Faber DS

    更新日期:2009-01-23 00:00:00

  • Effects of rimonabant on the reinstatement of nicotine-conditioned place preference by drug priming in rats.

    abstract::Drug addiction is a chronic disorder characterized by a relatively high rate of relapse even after long period of abstinence. In the present study, we used the conditioned place preference (CPP) paradigm to investigate the establishment, extinction, reinstatement and cross-reinstatement of nicotine-induced place condi...

    journal_title:Behavioural brain research

    pub_type: 杂志文章

    doi:10.1016/j.bbr.2009.03.042

    authors: Biala G,Budzynska B,Staniak N

    更新日期:2009-09-14 00:00:00

  • Isoorientin, a GSK-3β inhibitor, rescues synaptic dysfunction, spatial memory deficits and attenuates pathological progression in APP/PS1 model mice.

    abstract::β-Amyloid (Aβ) elevation, tau hyperphosphorylation, and neuroinflammation are major hallmarks of Alzheimer's disease (AD). Glycogen synthase kinase-3β (GSK-3β) is a key protein kinase implicated in the pathogenesis of AD. Blockade of GSK-3β is an attractive therapeutic strategy for AD. Isoorientin, a 6-C-glycosylflavo...

    journal_title:Behavioural brain research

    pub_type: 杂志文章

    doi:10.1016/j.bbr.2020.112968

    authors: Tan X,Liang Z,Li Y,Zhi Y,Yi L,Bai S,Forest KH,Nichols RA,Dong Y,Li QX

    更新日期:2021-02-01 00:00:00

  • Exposure to an enriched environment facilitates motor recovery and prevents short-term memory impairment and reduction of striatal BDNF in a progressive pharmacological model of parkinsonism in mice.

    abstract::Previous studies showed that the repeated administration with a low dose of reserpine (RES) induces a gradual appearance of motor signs and cognitive deficits compatible with parkinsonism in rodents. Environmental stimulation has neuroprotective effects in animal models of neurodegenerative damage, including acutely i...

    journal_title:Behavioural brain research

    pub_type: 杂志文章

    doi:10.1016/j.bbr.2017.04.028

    authors: Campêlo CLC,Santos JR,Silva AF,Dierschnabel AL,Pontes A,Cavalcante JS,Ribeiro AM,Silva RH

    更新日期:2017-06-15 00:00:00

  • David vs. Goliath: Serotonin modulates opponent perception between smaller and larger rivals.

    abstract::During agonistic encounters, the perception of a larger opponent through morphological signaling typically suppresses aggression in the smaller individual, preventing contest intensity escalation. However, non-morphological factors such as central serotonin (5-HT) activity can influence individual aggression, potentia...

    journal_title:Behavioural brain research

    pub_type: 杂志文章

    doi:10.1016/j.bbr.2015.07.028

    authors: Bubak AN,Rieger NS,Watt MJ,Renner KJ,Swallow JG

    更新日期:2015-10-01 00:00:00

  • Changes in sleep-waking cycle after striatal excitotoxic lesions.

    abstract::Huntington's disease (HD) patients show severe diurnal choreic movements, while during slow-wave sleep (SWS) abnormal movements subside. Sleep disturbances in HD, including irregular delta activity and decreases in SWS, have also been reported. Striatal excitotoxic lesions have been shown to induce increased nocturnal...

    journal_title:Behavioural brain research

    pub_type: 杂志文章

    doi:10.1016/s0166-4328(02)00201-2

    authors: Mena-Segovia J,Cintra L,Prospéro-García O,Giordano M

    更新日期:2002-11-15 00:00:00

  • Hand kinematics during reaching and grasping in the macaque monkey.

    abstract::In this paper, we develop an animal model of prehension movements by examining the kinematics of reaching and grasping in monkeys and by comparing the results to published data on humans. Hand movements were recorded in three dimensions in monkeys who were trained to either point at visual targets under unperturbed an...

    journal_title:Behavioural brain research

    pub_type: 杂志文章

    doi:10.1016/s0166-4328(00)00284-9

    authors: Roy AC,Paulignan Y,Farnè A,Jouffrais C,Boussaoud D

    更新日期:2000-12-20 00:00:00

  • Virtual environment navigation tasks and the assessment of cognitive deficits in individuals with brain injury.

    abstract::Navigation in real environments is often impaired by traumatic brain injury (TBI). These deficits in wayfinding appear to be due to disruption of cognitive processes underlying navigation and may in turn be due to damage to the hippocampus and frontal lobes. These wayfinding problems after TBI were investigated using ...

    journal_title:Behavioural brain research

    pub_type: 杂志文章

    doi:10.1016/j.bbr.2007.07.015

    authors: Livingstone SA,Skelton RW

    更新日期:2007-12-11 00:00:00

  • Pharmacological treatment to augment hole board habituation in prenatal Vitamin D-deficient rats.

    abstract::Neurocognitive impairment has consistently been considered a central and stable feature of schizophrenia. There is much controversy about the effects of neuroleptics on neurocognitive deficits. Thus, further investigations are needed to clarify the pathological substrate of cognitive deficits in schizophrenia as well ...

    journal_title:Behavioural brain research

    pub_type: 杂志文章

    doi:10.1016/j.bbr.2005.07.010

    authors: Becker A,Grecksch G

    更新日期:2006-01-06 00:00:00

  • Observations in THY-Tau22 mice that resemble behavioral and psychological signs and symptoms of dementia.

    abstract::THY-Tau22 mice constitute an animal model for tau aggregation, a hallmark in Alzheimer's disease (AD) and Tauopathies. Our previous studies have shown learning and memory deficits and changes in synaptic plasticity in the hippocampus in THY-Tau22 mice that are consistent with the learning impairments seen in AD-patien...

    journal_title:Behavioural brain research

    pub_type: 杂志文章

    doi:10.1016/j.bbr.2012.12.008

    authors: Van der Jeugd A,Blum D,Raison S,Eddarkaoui S,Buée L,D'Hooge R

    更新日期:2013-04-01 00:00:00

  • An integrative analysis to sleep functions.

    abstract::Various studies suggest that some sleep functions, especially some slow wave sleep functions, are indispensable in mammals and related to brain regulation. It has been proposed that two of these functions are the adjustment of emotional balance and the processing of acquired emotional memories. During waking, the grad...

    journal_title:Behavioural brain research

    pub_type: 杂志文章,评审

    doi:10.1016/0166-4328(95)00005-e

    authors: Cai ZJ

    更新日期:1995-07-01 00:00:00

  • Enhanced recovery of learned alternation in ganglioside-treated rats after unilateral entorhinal lesions.

    abstract::The present study demonstrates that an abbreviated regimen of ganglioside treatments attenuates the behavioral impairments produced by unilateral lesions of the entorhinal cortex. Ganglioside treatments not only accelerate recovery of learned alternation on a Y-maze, but also reduce total errors and perseverative erro...

    journal_title:Behavioural brain research

    pub_type: 杂志文章

    doi:10.1016/s0166-4328(05)80057-9

    authors: Ramirez JJ,Fass-Holmes B,Karpiak SE,Harshbarger R,Zengel D,Wright P,Valbuena M

    更新日期:1991-04-18 00:00:00