SUN11602, a bFGF mimetic, modulated neuroinflammation, apoptosis and calcium-binding proteins in an in vivo model of MPTP-induced nigrostriatal degeneration

Abstract

Background Parkinson’s disease (PD) is the second most frequent neurodegenerative disease. PD etiopathogenesis is multifactorial and not yet fully known, however, the scientific world advised the establishment of neuroinflammation among the possible risk factors. In this field, basic fibroblast growth factor/fibroblast growth factor receptor-1 (bFGF/FGFR1) could be a promising way to treat CNS-mediated inflammation; unfortunately, the use of bFGF as therapeutic agent is limited by its side effects. The novel synthetic compound SUN11602 exhibited neuroprotective activities like bFGF. With this perspective, this study aimed to evaluate the effect of SUN11602 administration in a murine model of MPTP-induced dopaminergic degeneration. Methods Specifically, nigrostriatal degeneration was induced by intraperitoneal injection of MPTP (80 mg/kg). SUN11602 (1 mg/kg, 2.5 mg/kg, and 5 mg/kg) was administered daily by oral gavage starting from 24 h after the first administration of MPTP. Mice were killed 7 days after MPTP induction. Results The results obtained showed that SUN11602 administration significantly reduced the alteration of PD hallmarks, attenuating the neuroinflammatory state via modulation of glial activation, NF-κB pathway, and cytokine overexpression. Furthermore, we demonstrated that SUN11602 treatment rebalanced Ca2+ overload in neurons by regulating Ca2+-binding proteins while inhibiting the apoptotic cascade. Conclusion Therefore, in the light of these findings, SUN11602 could be considered a valuable pharmacological strategy for PD.

Inhibition of LRRK2 Attenuates Depression-Related Symptoms in Mice with Moderate Traumatic Brain Injury

“…The elevated plus-maze was performed 24 days after mTBI, as previously described [ 18 ]. The EPM apparatus was made of metal and black plastic and consisted of two opposite open arms (45 cm × 10 cm) without side walls and two enclosed arms (45 cm × 10 cm × 30 cm) with sides and end walls, extending from a central square (10 cm × 10 cm).…”

Novel Findings on CCR1 Receptor in CNS Disorders: A Pathogenic Marker Useful in Controlling Neuroimmune and Neuroinflammatory Mechanisms in Parkinson’s Disease

“…For the experimental model, at day 0, male CD1 mice received four intraperitoneal injections of MPTP (20 mg/kg; Cayman Chemical Company, Ann Arbor, MI, USA) in saline at 2 h intervals; the total dose for each mouse was 80 mg/kg. The MPTP dose of 80 mg/kg was determined from previous in vivo research [48]. Starting 24 h after the first MPTP injection, animals received intraperitoneal administration of BX471 at doses of 3 mg/kg, 10 mg/kg, and 30 mg/kg.…”

“…Behavioral evaluations of each mouse were conducted seven days after the last MPTP injection. Before the onset of the behavioral tests, the animals were allowed to acclimate for 5 min for 2 days in the behavior room [48].…”

“…Under natural conditions, the mice will be oriented downwards along the length of the pole. The test's criteria were the amount of time the animal took to turn 180 degrees, or the turning time, and the total amount of time the animal took to descend to the ground [48].…”

“…All the mice were placed separately in the open arm and allowed to explore for five minutes. Animal behavior indications of its emotional state were identified to be the latency of attendance in both closed arms and the center [48].…”