What is hippocampal bdnf

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Lausanne 2 , Nowacka, M. Numakawa, T. Accumulating evidences link AD pathology with reduced BDNF levels in the serum 2 and in the cognition-related structures, such the as hippocampus and frontal cortex 3. BDNF is a prominent neurotrophin that regulates many of the hippocampus-based biological processes that include maintenance and survival of hippocampal neurons 4 , promoting hippocampal dendritic spine density and morphology 5 , and enhancing hippocampal neurogenesis 6.

Considering its essential role in providing trophic support to degenerating neurons and promoting postsynaptic functions, BDNF has, therefore, gained an enormous attention as a promising therapeutic target in countering AD pathology. Therefore, enhancing the production of BDNF in vivo in the hippocampus using safer and effective approaches is presently an important area of research.

In addition, we also noticed an improvement in hippocampus-based cognitive behaviors following oral administration of Hex in 5XFAD mice. These results highlight the protection of spatial learning and memory by a hippocampal drug in an animal model of AD. Hex upregulates the expression of BDNF in primary hippocampal neurons.

Together, these results suggest that Hex is capable of stimulating hippocampal BDNF and related neurotrophic molecules. Hex upregulates BDNF and other members of the neurotrophin family in the primary hippocampal neurons. Characterizing drugs for improving synaptic plasticity is an important area of research. Therefore, we examined whether oral administration of Hex could increase the level of Hex in the hippocampi of 5XFAD mice.

Moreover, the brain is also rich in FAAH 13 ; therefore, we decided to treat mice via gavage daily. These results demonstrate that after oral supplementation, Hex is capable of entering into the CNS and adding on to its endogenous levels in the hippocampus.

Next, we investigated whether this increased endogenous level of Hex could counter any of the AD-associated pathology. Because BDNF restoration plays a pivotal role in attenuating behavioral deficits, preventing neuron loss, alleviating synaptic degeneration, and reducing neuronal abnormality in different AD mouse models 14 , 15 , we investigated whether oral administration of Hex could influence hippocampal BDNF and other plasticity-related molecules in 5XFAD mice.

In addition to Bdnf gene, several other plasticity-associated genes e. We validated some of these plasticity-associated genes, including Bdnf , by Western blot. It has been reported that the level of postsynaptic density protein of 95 kDa PSD95 , involved in synaptic plasticity, is reduced in the hippocampi of 5XFAD mice 16 and patients with AD 17 , probably due to aberrant plaque and tangle formation and neuroinflammation.

As evident from our immunoblot analyses Figure 2C and corresponding densitometric analyses Figure 2G , oral administration of Hex significantly increased the level of PSD95 protein in the hippocampi of Hex-fed 5XFAD mice in comparison with vehicle-fed mice. To further characterize the role of Hex in the regulation of synaptic functions, we next investigated the expression of GLUR1 and NR2A, 2 proteins belonging to ionotropic glutamate receptor family that are long known to play important roles in postsynaptic calcium influx Together, these results indicate that Hex may control hippocampal plasticity by regulating the hippocampal expression of some of the notable plasticity-associated molecules.

Following 1 month of Hex treatment, the mRNA expression of several plasticity-associated genes was analyzed by real-time PCR, followed by gene array analysis. GAPDH was used as an endogenous control. B Venn diagram summarizing the numbers of differentially regulated plasticity genes. Relative expression greater than 2 was considered statistically significant. Uncropped Western blot images are shown in Supplemental Figure 6.

Hex promotes hippocampal synaptic functions in 5XFAD mice. It has been reported that cognitive decline positively correlates with reduced number of positive clusters for PSD95, an indicator of loss of actual synapses Therefore, we next explored a possible association of Hex-mediated upregulation of PSD95 with altered spine morphology.

Therefore, we immunolabeled the hippocampal slices harvested from mice across all groups with MAP2, a neuronal marker, and PSD In summary, Hex-mediated protective effects on postsynaptic marker clusters and calcium currents in the hippocampus suggest that Hex may ameliorate AD-associated cognitive defects by promoting these synaptic morphological and functional improvements.

The hippocampus is a region in the brain that is crucial for learning and memory. Previous researches proved that brain-derived neurotrophic factor BDNF is a probable responsible protein in the learning and memory formation process. PubMed Abstract Google Scholar. Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma.

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