Increased Level of β-Amyloid in the Brain of Bulbectomized Mice

Aleksandrova, I. Yu.; Kuvichkin, Vasily; Kashparov, I. A.; Medvinskaya, N. I.; Nesterova, I. V.; Лунин, С. М.; Samokhin, A. N.; Бобкова, Н. В.

doi:10.1023/b:biry.0000018948.04559.ab

Cited by 65 publications

(42 citation statements)

References 11 publications

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“…The olfactory dysfunction has been proposed to be the prodrome of AD, in which the hippocampus-dependent memory decline is generally the earliest clinical symptom of the patients [62]. The animal models with removal of olfactory bulb also show memory deficits [63], interneurons unnormally activated [64], and Aβ accumulation in the hippocampus [16], which resemble the observations in AD patients. These data suggest that the olfactory deficit may cause hippocampus impairments.…”

Section: Discussionmentioning

confidence: 87%

Activation of Glycogen Synthase Kinase-3 Mediates the Olfactory Deficit-Induced Hippocampal Impairments

Huang

Wang

et al. 2014

Mol Neurobiol

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The populations with olfactory dysfunction show an increased chance for hippocampus-dependent episodic memory deficit. Although it is known that the olfactory information projects to the hippocampus through entorhinal cortex layer II, the molecular mechanisms linking olfactory deficit to the hippocampus is not understood. Using bilateral olfactory bulbectomy (OBX) as a model, we found that OBX induced memory deficits with activation of several memory-related protein kinases in the hippocampal extracts, including glycogen synthase kinase-3β (GSK-3β), protein kinase A (PKA), extracellular-signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), phosphatidylinositol-3-kinase (PI3K), and protein kinase B (PKB). The OBX rats also show suppression of long-term potentiation (LTP); reduction of synapsin I, synaptophysin, NR2A/B, and PSD95; thinner presynaptic active zone and postsynaptic density with enlarged synaptic space; decreased spine numbers and mushroom-type spines; and tau hyperphosphorylation. After injection of SB216763 for several weeks by vena caudalis, selective inhibition of GSK-3β ameliorated the OBX-induced memory deficits with recovery of the synaptic components and tau phosphorylation. Furthermore, genetic ablation of GSK-3β by lentivirus-packed shRNA effectively rescued the memory deficits, synaptic disorder, and tauopathy. Our data indicate that GSK-3 activation mediates the olfactory deficits to the hippocampus, and targeting GSK-3 blocks the pathological connection.

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Section: Discussionmentioning

confidence: 87%

Activation of Glycogen Synthase Kinase-3 Mediates the Olfactory Deficit-Induced Hippocampal Impairments

Huang

Wang

et al. 2014

Mol Neurobiol

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“…Moreover, OBX has been used as one of the AD models since impairment of olfactory perceptual acuity is observed not only at the early stage of AD (14,15) but also in a transgenic AD model of mice over-expressing a mutant form of the human amyloid-bprecursor protein (16). In addition, OBX causes elevation of the Ab level in the brain (17) and the degeneration of septo-hippocampal cholinergic system in rodents (8,9,18), and thereby induces cognitive dysfunction (8 -10).…”

Section: Butea Superba-induced Amelioration Of Cognitive and Emotionamentioning

confidence: 99%

Butea superba–Induced Amelioration of Cognitive and Emotional Deficits in Olfactory Bulbectomized Mice and Putative Mechanisms Underlying Its Actions

et al. 2014

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Abstract. This study investigated the effects of alcoholic extract of Butea superba (BS) on cognitive deficits and depression-related behavior using olfactory bulbectomized (OBX) mice and the underlying molecular mechanisms of its actions. OBX mice were treated daily with BS (100 and 300 mg/kg, p.o.) or reference drugs, tacrine (2.5 mg/kg, i.p.) and imipramine (10 mg/kg, i.p.) from day 3 after OBX. OBX impaired non-spatial and spatial cognitive performances, which were elucidated by the novel object recognition test and modified Y maze test, respectively. These deficits were attenuated by tacrine and BS but not imipramine. OBX animals exhibited depressionlike behavior in the tail suspension test in a manner reversible by imipramine and BS but not tacrine. OBX down-regulated phosphorylation of synaptic plasticity-related signaling proteins: NMDA receptor, AMPA receptor, calmodulin-dependent kinase II, and cyclic AMP-responsive element-binding protein. OBX also reduced choline acetyltransferase in the hippocampus. BS and tacrine reversed these neurochemical alterations. Moreover, BS inhibited ex vivo activity of acetylcholinesterase in the brain. These results indicate that BS ameliorates not only cognition dysfunction via normalizing synaptic plasticity-related signaling and facilitating central cholinergic systems but also depression-like behavior via a mechanism differing from that implicated in BS amelioration of cognitive function in OBX animals.

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“…95 Because of its cholinergic alterations, the OBX rats are also used as a model of Alzheimer's disease, as there is an elevation of beta-amyloid in the rat brain after bulbectomy. 96 …”

Section: Acetylcholine System Alteration In Obx Ratsmentioning

confidence: 99%

Neurochemical and Behavioural Changes in Rat Models of Depression

Skelin¹,

Kovačević²,

Dikšić³

2011

Croat. Chem. Acta

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Abstract. Depression is one of the most prevalent psychiatric disorders with significant lifetime prevalence. The study of human depression is hindered by the relatively significant heterogeneity of this disorder. As a result of these heterogeneities, studies using a sound and representative animal model of depression are extremely valuable and, in general, provide important information regarding the neurochemical/biological changes occurring during depression and the subsequent treatment of its symptoms. In this review we concentrate on two solid rat models of depression: olfactory bulbectomized (OBX) rats and Flinders Sensitive Line (FSL) of rats. These two models were selected because they possess all three characteristics of a good animal model; face, predictive and constructive validities. We also emphasize the brain serotonergic system and we discuss the open field and forced swim test to assess behaviour. (doi: 10.5562/cca1817) Keywords: depression, olfactory bulbectomized rat model of depression, Flinders sensitive line rat, Flinders Resistant line rat, animal model of depression

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Increased Level of β-Amyloid in the Brain of Bulbectomized Mice

Cited by 65 publications

References 11 publications

Activation of Glycogen Synthase Kinase-3 Mediates the Olfactory Deficit-Induced Hippocampal Impairments

Activation of Glycogen Synthase Kinase-3 Mediates the Olfactory Deficit-Induced Hippocampal Impairments

Butea superba–Induced Amelioration of Cognitive and Emotional Deficits in Olfactory Bulbectomized Mice and Putative Mechanisms Underlying Its Actions

Neurochemical and Behavioural Changes in Rat Models of Depression

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