Abstract:Brain derived neurotrophic factor (BDNF) plays a pivotal role in structural plasticity, learning, and memory. Electroencephalogram (EEG) spectral power in the cortex and hippocampus has also been correlated with learning and memory. In this study, we investigated the effect of globally reduced BDNF levels on learning behavior and EEG power via BDNF heterozygous (KO) rats. We employed several behavioral tests that are thought to depend on cortical and hippocampal plasticity to varying degrees: novel object reco… Show more
“…qRT-PCR of hippocampal tissue showed that the single FLRT2 allele deletion results in a reduction of the FLRT2 mRNA levels in both in male (~47% reduction) and in female (~40% reduction) mice (Fig. 1E ), which is in agreement with the inhibition in the level of expression of specific proteins in other studied single-allele knockout mice 24 – 26 . Figure 1 FLRT2+/− mice do not present with gross, detectable phenotypical abnormalities.…”
Section: Resultssupporting
confidence: 85%
“…Conventional full knockouts animals were not used in the present study as previous reports demonstrated that the vast majority of homozygous FLRT2 knockout animals die at embryonic day 12–15 18 , 22 and therefore cannot be used to study the importance of FLRT2 in postnatal brain functions. The use of heterozygous knockout animals constitute a widely accepted tool for the identification of molecular components implicated in the regulation of synaptic plasticity and higher order cognitive functions 24 – 26 . Our observations of the effects of the genetic suppression of FLRT2 via haplodeficiency in female and male mice propose FLRT2 as a critical molecular component regulating adult synaptic plasticity and suggest a sex-dependent implication of FLRT2 in the promotion of hippocampus-dependent memory functions.…”
The Fibronectin Leucine-Rich Transmembrane protein 2 (FLRT2) has been implicated in several hormone -and sex-dependent physiological and pathological processes (including chondrogenesis, menarche and breast cancer); is known to regulate developmental synapses formation, and is expressed in the hippocampus, a brain structure central for learning and memory. However, the role of FLRT2 in the adult hippocampus and its relevance in sex-dependent brain functions remains unknown. We here used adult single-allele FLRT2 knockout (FLRT2+/−) mice and behavioral, electrophysiological, and molecular/biological assays to examine the effects of FLRT2 haplodeficiency on synaptic plasticity and hippocampus-dependent learning and memory. Female and male FLRT2+/− mice presented morphological features (including body masses, brain shapes/weights, and brain macroscopic cytoarchitectonic organization), indistinguishable from their wild type counterparts. However, in vivo examinations unveiled enhanced hippocampus-dependent spatial memory recall in female FLRT2+/− animals, concomitant with augmented hippocampal synaptic plasticity and decreased levels of the glutamate transporter EAAT2 and beta estrogen receptors. In contrast, male FLRT2+/− animals exhibited deficient memory recall and decreased alpha estrogen receptor levels. These observations propose that FLRT2 can regulate memory functions in the adulthood in a sex-specific manner and might thus contribute to further research on the mechanisms linking sexual dimorphism and cognition.
“…qRT-PCR of hippocampal tissue showed that the single FLRT2 allele deletion results in a reduction of the FLRT2 mRNA levels in both in male (~47% reduction) and in female (~40% reduction) mice (Fig. 1E ), which is in agreement with the inhibition in the level of expression of specific proteins in other studied single-allele knockout mice 24 – 26 . Figure 1 FLRT2+/− mice do not present with gross, detectable phenotypical abnormalities.…”
Section: Resultssupporting
confidence: 85%
“…Conventional full knockouts animals were not used in the present study as previous reports demonstrated that the vast majority of homozygous FLRT2 knockout animals die at embryonic day 12–15 18 , 22 and therefore cannot be used to study the importance of FLRT2 in postnatal brain functions. The use of heterozygous knockout animals constitute a widely accepted tool for the identification of molecular components implicated in the regulation of synaptic plasticity and higher order cognitive functions 24 – 26 . Our observations of the effects of the genetic suppression of FLRT2 via haplodeficiency in female and male mice propose FLRT2 as a critical molecular component regulating adult synaptic plasticity and suggest a sex-dependent implication of FLRT2 in the promotion of hippocampus-dependent memory functions.…”
The Fibronectin Leucine-Rich Transmembrane protein 2 (FLRT2) has been implicated in several hormone -and sex-dependent physiological and pathological processes (including chondrogenesis, menarche and breast cancer); is known to regulate developmental synapses formation, and is expressed in the hippocampus, a brain structure central for learning and memory. However, the role of FLRT2 in the adult hippocampus and its relevance in sex-dependent brain functions remains unknown. We here used adult single-allele FLRT2 knockout (FLRT2+/−) mice and behavioral, electrophysiological, and molecular/biological assays to examine the effects of FLRT2 haplodeficiency on synaptic plasticity and hippocampus-dependent learning and memory. Female and male FLRT2+/− mice presented morphological features (including body masses, brain shapes/weights, and brain macroscopic cytoarchitectonic organization), indistinguishable from their wild type counterparts. However, in vivo examinations unveiled enhanced hippocampus-dependent spatial memory recall in female FLRT2+/− animals, concomitant with augmented hippocampal synaptic plasticity and decreased levels of the glutamate transporter EAAT2 and beta estrogen receptors. In contrast, male FLRT2+/− animals exhibited deficient memory recall and decreased alpha estrogen receptor levels. These observations propose that FLRT2 can regulate memory functions in the adulthood in a sex-specific manner and might thus contribute to further research on the mechanisms linking sexual dimorphism and cognition.
“…For spectral power analysis, amplified and filtered cortical EEG data were digitized at a sampling frequency of 200 Hz, as described previously [ 31 , 63 ]. The digitized data were then subjected to a fast Fourier transformation from 0.5 to 100 Hz with an interval of 0.2 Hz.…”
Study ObjectivesBrain-derived neurotrophic factor (BDNF) expression and homeostatic regulation of rapid eye movement (REM) sleep are critical for neurogenesis and behavioral plasticity. Accumulating clinical and experimental evidence suggests that decreased BDNF expression is causally linked with the development of REM sleep-associated neuropsychiatric disorders. Therefore, we hypothesize that BDNF plays a role in sleep–wake (S–W) activity and homeostatic regulation of REM sleep.MethodsMale and female wild-type (WT; BDNF +/+) and heterozygous BDNF (KD; BDNF +/−) rats were chronically implanted with S–W recording electrodes to quantify baseline S–W activity and REM sleep homeostatic regulatory processes during the light phase.ResultsMolecular analyses revealed that KD BDNF rats had a 50% decrease in BDNF protein levels. During baseline S–W activity, KD rats exhibited fewer REM sleep episodes that were shorter in duration and took longer to initiate. Also, the baseline S–W activity did not reveal any sex difference. During the 3-hour selective REM sleep deprivation, KD rats failed to exhibit a homeostatic drive for REM sleep and did not exhibit rebound REM sleep during the recovery S–W period.ConclusionInterestingly, both genotypes did not reveal any sex difference in the quality and/or quantity of REM sleep. Collectively, these results, for the first time, unequivocally demonstrate that an intact BDNF system in both sexes is a critical modulator for baseline and homeostatic regulation of REM sleep. This study further suggests that heterozygous BDNF knockdown rats are a useful animal model for the study of the cellular and molecular mechanisms of sleep regulation and cognitive functions of sleep.
“…Our previous study confirmed that HBO preconditioning promoted neovascularization via increasing the expression levels of SDF-1 and CXCR4 in transplanted skin flaps of rats [9] . Brain-derived neurotrophic factor (BDNF) has a pivotal role in structural plasticity, learning, and memory [10] . It prevents neurodegeneration and acts as one of the synaptic plasticity markers.…”
Background:Spinal cord injury (SCI) is a worldwide medical concern. This study aimed to elucidate the mechanism underlying the protective effect of hyperbaric oxygen (HBO) against SCI-induced neurologic defects in rats via exploring the stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) axis and expression of brain-derived neurotrophic factor (BDNF).Methods:An acute SCI rat model was established in Sprague-Dawley rats using the Allen method. Sixty rats were divided into four groups (n = 15 in each group): sham-operated, SCI, SCI treated with HBO (SCI + HBO), and SCI treated with both HBO and AMD3100 (an antagonist of CXCR4; SCI + HBO + AMD) groups. The rats were treated with HBO twice a day for 3 days and thereafter once a day after the surgery for up to 28 days. Following the surgery, neurologic assessments were performed with the Basso-Bettie-Bresnahan (BBB) scoring system on postoperative day (POD) 7, 14, 21, and 28. Spinal cord tissues were harvested to assess the expression of SDF-1, CXCR4, and BDNF at mRNA and protein levels, using quantitative real-time polymerase chain reaction, Western blot analysis, and histopathologic analysis.Results:HBO treatment recovered SCI-induced descent of BBB scores on POD 14, (1.25 ± 0.75 vs. 1.03 ± 0.66, P < 0.05), 21 (5.27 ± 0.89 vs. 2.56 ± 1.24, P < 0.05), and 28 (11.35 ± 0.56 vs. 4.23 ± 1.20, P < 0.05) compared with the SCI group. Significant differences were found in the mRNA levels of SDF-1 (mRNA: day 21, SCI + HBO vs. SCI + HBO + AMD, 2.89 ± 1.60 vs. 1.56 ± 0.98, P < 0.05), CXCR4 (mRNA: day 7, SCI + HBO vs. SCI, 2.99 ± 1.60 vs.1.31 ± 0.98, P < 0.05; day 14, SCI + HBO vs. SCI + HBO + AMD, 4.18 ± 1.60 vs. 0.80 ± 0.34, P < 0.05; day 21, SCI + HBO vs. SCI, 2.10 ± 1.01 vs.1.15 ± 0.03, P < 0.05), and BDNF (mRNA: day 7, SCI + HBO vs. SCI, 3.04 ± 0.41 vs. 2.75 ± 0.31, P < 0.05; day 14, SCI + HBO vs. SCI, 3.88 ± 1.59 vs. 1.11 ± 0.40, P < 0.05), indicating the involvement of SDF-1/CXCR4 axis in the protective effect of HBO.Conclusions:HBO might promote the recovery of neurologic function after SCI in rats via activating the SDF-1/CXCR4 axis and promoting BDNF expression.
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