Hypothalamic Adult Neurogenesis (hAN) has been implicated in regulating energy homeostasis. Adult-generated neurons and adult Neural Stem Cells (aNSCs) in the hypothalamus control food intake and body weight. Conversely, diet-induced obesity (DIO) by high fat diets (HFD) exerts adverse influence on hAN. However, the effects of anti-obesity compounds on hAN are not known. To address this, we administered a lipidized analogue of an anti-obesity neuropeptide, Prolactin Releasing Peptide (PrRP), so-called LiPR, to mice. In the HFD context, LiPR rescued the survival of adult-born hypothalamic neurons and increased the number of aNSCs by reducing their activation. LiPR also rescued the reduction of immature hippocampal neurons and modulated calcium dynamics in iPSC-derived human neurons. In addition, some of these neurogenic effects were exerted by another anti-obesity compound, Liraglutide. These results show for the first time that anti-obesity neuropeptides influence adult neurogenesis and suggest that the neurogenic process can serve as a target of anti-obesity pharmacotherapy.
[K(+)](e) increase accompanies many pathological states in the CNS and evokes changes in astrocyte morphology and glial fibrillary acidic protein expression, leading to astrogliosis. Changes in the electrophysiological properties and volume regulation of astrocytes during the early stages of astrocytic activation were studied using the patch-clamp technique in spinal cords from 10-day-old rats after incubation in 50 mM K(+). In complex astrocytes, incubation in high K(+) caused depolarization, an input resistance increase, a decrease in membrane capacitance, and an increase in the current densities (CDs) of voltage-dependent K(+) and Na(+) currents. In passive astrocytes, the reversal potential shifted to more positive values and CDs decreased. No changes were observed in astrocyte precursors. Under hypotonic stress, astrocytes in spinal cords pre-exposed to high K(+) revealed a decreased K(+) accumulation around the cell membrane after a depolarizing prepulse, suggesting altered volume regulation. 3D confocal morphometry and the direct visualization of astrocytes in enhanced green fluorescent protein/glial fibrillary acidic protein mice showed a smaller degree of cell swelling in spinal cords pre-exposed to high K(+) compared to controls. We conclude that exposure to high K(+), an early event leading to astrogliosis, caused not only morphological changes in astrocytes but also changes in their membrane properties and cell volume regulation.
- MeSH
- astrocyty fyziologie MeSH
- draslík farmakokinetika MeSH
- draslíkové kanály řízené napětím fyziologie MeSH
- financování organizované MeSH
- gliový fibrilární kyselý protein metabolismus MeSH
- glióza patofyziologie MeSH
- hypotonické roztoky farmakologie MeSH
- imunohistochemie MeSH
- koncentrace vodíkových iontů MeSH
- krysa rodu rattus MeSH
- membránové potenciály fyziologie účinky léků MeSH
- metoda terčíkového zámku MeSH
- mícha cytologie MeSH
- osmotický tlak MeSH
- potkani Wistar MeSH
- sodík metabolismus MeSH
- sodíkové kanály fyziologie MeSH
- velikost buňky MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
