RESUMEN
Both human and animal experiments have demonstrated that energy metabolism dysfunction in neurons after seizures is associated with an imbalance in mitochondrial fusion/fission dynamics. Effective neuronal mitochondrial dynamics regulation strategies remain elusive. Nicotinamide mononucleotide (NMN) can ameliorate mitochondrial functional and oxidative stress in age-related diseases. But whether NMN improves mitochondrial energy metabolism to exert anti-epileptic effects is unclear. This study aims to clarify if NMN can protect neurons from pentylenetetrazole (PTZ) or Mg2+ -free-induced mitochondrial disorder and apoptosis via animal and cell models. We established a continuous 30-day PTZ (37 mg/kg) intraperitoneal injection-induced epileptic mouse model and a cell model induced by Mg2+ -free solution incubation to explore the neuroprotective effects of NMN. We found that NMN treatment significantly reduced the seizure intensity of PTZ-induced epileptic mice, improved their learning and memory ability, and enhanced their motor activity and exploration desire. At the same time, in vitro and in vivo experiments showed that NMN can inhibit neuronal apoptosis and improve the mitochondrial energy metabolism function of neurons. In addition, NMN down-regulated the expression of mitochondrial fission proteins (Drp1 and Fis1) and promoted the expression of mitochondrial fusion proteins (Mfn1 and Mfn2) by activating the SIRT1-PGC-1α pathway, thereby inhibiting PTZ or Mg2+ -free extracellular solution-induced mitochondrial dysfunction, cell apoptosis, and oxidative stress. However, combined intervention of SIRT1 inhibitor, Selisistat, and PGC-1α inhibitor, SR-18292, eliminated the regulatory effect of NMN pre-treatment on mitochondrial fusion and fission proteins and apoptosis-related proteins. Therefore, NMN intervention may be a new potential treatment for cognitive impairment and behavioral disorders induced by epilepsy, and targeting the SIRT1-PGC-1α pathway may be a promising therapeutic strategy for seizures.
RESUMEN
The François' langur (Trachypithecus francoisi) is an endangered primate living in limestone forests in Vietnam and China. From October 2017 to August 2018, the habitat preferences and the range of the Francois' langur were surveyed in the Mayanghe Nature Reserve, Guizhou, People's Republic of China. To estimate the range and predict suitable habitat of François' langur, a Gaussian normal kernel density estimation and species distribution models (BIOMOD2) were used along with data on environmental variables and records of the langur's occurrence. The total range of François' langur in the reserve is 68.76 km2, accounting for 22.1% of the total area of the reserve. The elevation of the main utilisation area is 500-800 m, accounting for 48.53% of the total area of the reserve. The maximum slope utilised is 20°-30°, 30.19 km2 and accounting for 30.56% of the total area. The habitat used is largely distributed along valleys, preferred broad leaf forest, lower elevation, and close to rivers. Broad leaf forest is the main habitat type utilised, totalling 25.57 km2 and accounting for 37.19% of the total area. Our models predicted that the suitable habitat in the reserve is 62.46 km2, accounting for 20.08% of the total reserve area, with 32.93-km2 suitable habitat occurring in the core zone, 22.44 km2 in the buffer zone, and 7.02 km2 in the experimental zone. Our results indicate that only limited suitable habitat (51%) adverse reserve zoning exists in the Mayanghe Nature Reserve of François' langur.
