A key role for TGF-β1 in hippocampal synaptic plasticity and memory

Caraci, Filippo; Gulisano, Walter; Guida, Chiara; Impellizzeri, Agata Antonia Rita; Drago, Filippo; Puzzo, Daniela; Palmeri, Agostino

doi:10.1038/srep11252

Cited by 101 publications

(75 citation statements)

References 30 publications

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“…Furthermore, TGF-β signaling was one of the top scored pathways along with prion diseases pathway. Dysregulation of TGF-β pathway in AD and the protective role of TGF-β1 toward brain neuroinflammatory processes were previously reported (Caraci et al, 2008, 2011, 2015; Chen et al, 2015). Furthermore, we have previously found that TGF-β1 administration can revert the increase in Bax/Bcl2 ratio induced in rat retina following intravitreal administration of Aβ oligomers (Fisichella et al, 2016).…”

Section: Discussionmentioning

confidence: 71%

Retinal and Circulating miRNAs in Age-Related Macular Degeneration: An In vivo Animal and Human Study

et al. 2017

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Age related macular degeneration (AMD) is the leading cause of blindness among people aged 50 and over. Retinal deposition of amyloid-β (Aβ) aggregates in AMD patients has suggested a potential link between AMD and Alzheimer's disease (AD). We have evaluated the differential retinal expression profile of miRNAs in a rat model of AMD elicited by Aβ. A serum profile of miRNAs in AMD patients has been also assessed using single TaqMan assay. Analysis of retina from rats intravitreally injected with Aβ revealed that miR-27a, miR-146a, and miR-155 were up-regulated in comparison to control rats. Seven miRNA (miR-9, miR-23a, miR-27a, miR-34a, miR-126, miR-146a, and miR-155) have been found to be dysregulated in serum of AMD patients in comparison to control group. Analysis of pathways has revealed that dysregulated miRNAs, both in the AMD animal model and in AMD patients, can target genes regulating pathways linked to neurodegeneration and inflammation, reinforcing the hypothesis that AMD is a protein misfolding disease similar to AD. In fact, miR-9, miR-23a, miR-27a, miR-34a, miR-146a, miR-155 have been found to be dysregulated both in AMD and AD. In conclusion, we suggest that miR-9, miR-23a, miR-27a, miR-34a, miR-146a, miR-155 represent potential biomarkers and new pharmacological targets for AMD.

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Section: Discussionmentioning

confidence: 71%

Retinal and Circulating miRNAs in Age-Related Macular Degeneration: An In vivo Animal and Human Study

et al. 2017

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“…Moreover, it has been reported that PDE4 inhibition can also reduce neuroinflammation by dampening the production of the proinflammatory cytokines IL-1b and TNFα and by increasing the levels of TGFβ-1 and BDNF, which are known to play a key role in hippocampal synaptic plasticity and memory495051.…”

Section: Discussionmentioning

confidence: 99%

Memory-enhancing effects of GEBR-32a, a new PDE4D inhibitor holding promise for the treatment of Alzheimer’s disease

Ricciarelli

Brullo

Prickaerts

et al. 2017

Sci Rep

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Memory loss characterizes several neurodegenerative disorders, including Alzheimer’s disease (AD). Inhibition of type 4 phosphodiesterase (PDE4) and elevation of cyclic adenosine monophosphate (cAMP) has emerged as a promising therapeutic approach to treat cognitive deficits. However, PDE4 exists in several isoforms and pan inhibitors cannot be used in humans due to severe emesis. Here, we present GEBR-32a, a new PDE4D full inhibitor that has been characterized both in vitro and in vivo using biochemical, electrophysiological and behavioural analyses. GEBR-32a efficiently enhances cAMP in neuronal cultures and hippocampal slices. In vivo pharmacokinetic analysis shows that GEBR-32a is rapidly distributed within the central nervous system with a very favourable brain/blood ratio. Specific behavioural tests (object location and Y-maze continuous alternation tasks) demonstrate that this PDE4D inhibitor is able to enhance memory in AD transgenic mice and concomitantly rescues their hippocampal long-term potentiation deficit. Of great relevance, our preliminary toxicological analysis indicates that GEBR-32a is not cytotoxic and genotoxic, and does not seem to possess emetic-like side effects. In conclusion, GEBR-32a could represent a very promising cognitive-enhancing drug with a great potential for the treatment of Alzheimer’s disease.

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“…In hippocampal slices, it has been shown that LTP is dose-dependently weakened by a long-lasting TNF-α application [28]. The reduction in the level of TGF-β expression due to the use of LPS may also impair LTP induction [29].…”

Section: Introductionmentioning

confidence: 99%

Administration of Bacterial Lipopolysaccharide during Early Postnatal Ontogenesis Induces Transient Impairment of Long-Term Synaptic Plasticity Associated with Behavioral Abnormalities in Young Rats

et al. 2020

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Infectious diseases in early postnatal ontogenesis often result in cognitive impairments, particularly learning and memory. The essential foundation of learning and memory is long-term synaptic plasticity, which depends on N-methyl-D-aspartate (NMDA) receptors. In the present study, bacterial infection was modeled by treating rat pups with bacterial lipopolysaccharide (LPS, 25 µg/kg) three times, during either the first or the third week of life. These time points are critical for the maturation of NMDA receptors. We assessed the effects of LPS treatments on the properties of long-term potentiation (LTP) in the CA1 hippocampus of young (21-23 days) and adolescent (51-55 days) rats. LTP magnitude was found to be significantly reduced in both groups of young rats, which also exhibited investigative and motor behavior disturbances in the open field test. No changes were observed in the main characteristics of synaptic transmission, although the LTP induction mechanism was disturbed. In rats treated with LPS during the third week, the NMDA-dependent form of LTP was completely suppressed, and LTP switched to the Type 1 metabotropic glutamate receptor (mGluR1)-dependent form. These impairments of synaptic plasticity and behavior were temporary. In adolescent rats, no difference was observed in LTP properties between the control and experimental groups. Lastly, the investigative and motor behavior parameters in both groups of adult rats were similar.

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A key role for TGF-β1 in hippocampal synaptic plasticity and memory

Cited by 101 publications

References 30 publications

Retinal and Circulating miRNAs in Age-Related Macular Degeneration: An In vivo Animal and Human Study

Retinal and Circulating miRNAs in Age-Related Macular Degeneration: An In vivo Animal and Human Study

Memory-enhancing effects of GEBR-32a, a new PDE4D inhibitor holding promise for the treatment of Alzheimer’s disease

Administration of Bacterial Lipopolysaccharide during Early Postnatal Ontogenesis Induces Transient Impairment of Long-Term Synaptic Plasticity Associated with Behavioral Abnormalities in Young Rats

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