Infusion of BDNF into the nucleus accumbens of aged rats improves cognition and structural synaptic plasticity through PI3K-ILK-Akt signaling

Li, Min; Dai, Fang; Du, Xiaoping; Yang, Qidong; Zhang, Xiuwu; Chen, Yuxiang

doi:10.1016/j.bbr.2012.03.010

Cited by 59 publications

(41 citation statements)

References 36 publications

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“…BDNF has been shown to be closely involved in synaptic plasticity, which is crucial for learning and memory functions. It has been shown that infusion of BDNF in the nucleus accumbens of old aged rats restored synaptic plasticity and improved cognition (Li et al, 2012). In our present study, we found decreased hippocampal BDNF mRNA expression levels in both male and female VPAexposed rats.…”

Section: Discussionsupporting

confidence: 72%

Social behavior, neuroimmune markers and glutamic acid decarboxylase levels in a rat model of valproic acid-induced autism

Win-Shwe

Nway²,

Imai

et al. 2018

J. Toxicol. Sci.

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Autism is a complex neurodevelopmental disorder characterized by impaired social communication and social interactions, and repetitive behaviors. The etiology of autism remains unknown and its molecular basis is not yet well understood. Pregnant Sprague-Dawley (SD) rats were administered 600 mg/kg of valproic acid (VPA) by intraperitoneal injection on day 12.5 of gestation. Both 11-to 13-week-old male and female rat models of VPA-induced autism showed impaired sociability and impaired preference for social novelty as compared to the corresponding control SD rats. Significantly reduced mRNA expressions of social behavior-related genes, such as those encoding the serotonin receptor, brain-derived neurotrophic factor and neuroligin3, and significantly increased expression levels of proinflammatory cytokines, such as interleukin-1 β and tumor necrosis factor-α, were noted in the hippocampi of both male and female rats exposed to VPA in utero. The hippocampal expression level of gamma amino butyric acid (GABA) enzyme glutamic acid decarboxylase (GAD) 67 protein was reduced in both male and female VPA-exposed rats as compared to the corresponding control animals. Our results indicate that developmental exposure to VPA affects the social behavior in rats by modulating the expression levels of social behavior-related genes and inflammatory mediators accompanied with changes in GABA enzyme in the hippocampus.

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Section: Discussionsupporting

confidence: 72%

Social behavior, neuroimmune markers and glutamic acid decarboxylase levels in a rat model of valproic acid-induced autism

Win-Shwe

Nway²,

Imai

et al. 2018

J. Toxicol. Sci.

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“…One potential explanation is that withdrawal from repeated binge alcohol consumption produced an alteration in the function of mGlu1/5 that was reflected in the decrease in the phosphorylation of downstream signaling molecules (for more detailed discussion, see Cozzoli et al 2014b). However, another possible explanation is that the present results argue against a link between mGlu1/5 and PI3K in terms of binge alcohol effects, given that PI3K is a common transduction pathway for receptors such as tyrosine kinase B (TrkB), insulin-like growth factor-1 (IGF-1), and serotonin 1A (5HT 1A ; see Figure 1 in Banerjee et al, 2012; Li and Jope, 2010), which are all localized in the NAC (e.g., Araujo et al, 1989; Clissold et al, 2013; Li et al, 2012). Thus, it should be considered that binge alcohol produced an effect on PI3K signaling in males in the present study that was independent of an effect on mGlu1/5.…”

Section: Discussionmentioning

confidence: 67%

Functional regulation of PI3K-associated signaling in the accumbens by binge alcohol drinking in male but not female mice

et al. 2016

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It is well established that binge alcohol consumption produces alterations in Group 1 metabotropic glutamate receptors (mGlus) and related signaling cascades in the nucleus accumbens (NAC) of adult male mice, but female and adolescent mice have not been examined. Thus, the first set of studies determined whether repeated binge alcohol consumption produced similar alterations in protein and mRNA levels of Group 1 mGlu-associated signaling molecules in the NAC of male and female adult and adolescent mice. The adult (9 weeks) and adolescent (4 weeks) C57BL/6J mice were exposed to 7 binge alcohol sessions every 3rd day while controls drank water. Repeated binge alcohol consumption produced sexually divergent changes in protein levels and mRNA expression for Group 1 mGlus and downstream signaling molecules in the NAC, but there was no effect of age. Binge alcohol intake decreased mGlu5 levels in females, whereas it decreased indices of phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), 4E-binding protein 1, and p70 ribosomal protein S6 kinase in males. Expression of genes encoding mGlu1, mGlu5, the NR2A subunit of the NMDA receptor, and Homer2 were all decreased by binge alcohol consumption in males, while females were relatively resistant (only phosphoinositide-dependent protein kinase 1 was decreased). The functional implication of these differences was investigated in a separate study by inhibiting mTOR in the NAC (via infusions of rapamycin) before binge drinking sessions. Rapamycin (50 and 100 ng/side) significantly decreased binge alcohol consumption in males, while consumption in females was unaffected. Altogether these results highlight that mTOR signaling in the NAC was necessary to maintain binge alcohol consumption only in male mice and that binge drinking recruits sexually divergent signaling cascades downstream of PI3K and presumably, Group 1 mGlus. Importantly, these findings emphasize that sex should be considered in the development of potential pharmacotherapeutic targets.

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“…The frontal medial cortex corresponds to Brodmann areas 11 and 12 located in the medial part of the orbitofrontal area (Rademacher et al ., ). The VST consists of the nucleus accumbens and ventral parts of the caudate nucleus and putamen (Mawlawi et al ., ; Martinez et al ., ), and its associations with cognition, as well as behavior, are well known (Diekhof et al ., ; de Jong et al ., ; Li et al ., ). Anatomically, the VST receives both focal and diffuse projections from different prefrontal subregions, predominantly from the medial part of the prefrontal area (Ferry et al ., ; Ongur & Price, ), and it is also functionally linked to the medial part of the orbitofrontal area (Di Martino et al ., ; Jung et al ., ).…”

Section: Discussionmentioning

confidence: 97%

Regional analysis of striatal and cortical amyloid deposition in patients with Alzheimer's disease

Ishibashi

Ishiwata

Toyohara

et al. 2014

Eur J of Neuroscience

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We aimed to analyse the detailed distribution pattern of amyloid-β (Aβ) in the striatum, and to examine whether there is any correlation between Aβ deposition levels in the striatum and cortical regions. Twenty patients with Alzheimer's disease underwent positron emission tomography using (11) C-Pittsburgh Compound B ((11) C-PiB) to quantify the Aβ deposition. Volumes-of-interest analyses were performed on the ventral striatum (VST), pre-commissural dorsal caudate (pre-DCA), post-commissural caudate (post-CA), pre-commissural dorsal putamen (pre-DPU), and post-commissural putamen (post-PU), followed by exploratory voxel-wise analyses. Volumes-of-interest analyses of (11) C-PiB binding showed: VST > pre-DPU (P = 0.004), VST > pre-DCA (P < 0.0001), pre-DPU > post-PU (P < 0.0001), and pre-DCA > post-CA (P < 0.0001), consistent with visual inspection of the (11) C-PiB images. Exploratory voxel-wise analyses of (11) C-PiB binding showed a positive correlation between the VST and the medial part of the orbitofrontal area (P < 0.01 family-wise error corrected). This study confirmed that there were ventral > dorsal, and anterior > posterior gradients of Aβ deposition in patients with Alzheimer's disease, and provided the first evidence of a robust correlation between Aβ deposition levels in the VST and the medial part of the orbitofrontal area. There are well-known anatomical and functional links between these areas. These findings indicated that brain Aβ deposition was not randomly distributed, but had characteristic patterns related to anatomical connectivity and/or functional networks.

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Infusion of BDNF into the nucleus accumbens of aged rats improves cognition and structural synaptic plasticity through PI3K-ILK-Akt signaling

Cited by 59 publications

References 36 publications

Social behavior, neuroimmune markers and glutamic acid decarboxylase levels in a rat model of valproic acid-induced autism

Social behavior, neuroimmune markers and glutamic acid decarboxylase levels in a rat model of valproic acid-induced autism

Functional regulation of PI3K-associated signaling in the accumbens by binge alcohol drinking in male but not female mice

Regional analysis of striatal and cortical amyloid deposition in patients with Alzheimer's disease

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