Nicotine Significantly Improves Chronic Stress-Induced Impairments of Cognition and Synaptic Plasticity in Mice

Abstract

The aim of this study was to examine if nicotine was able to improve cognition deficits in a mouse model of chronic mild stress. Twenty-four male C57BL/6 mice were divided into three groups: control, stress, and stress with nicotine treatment. The animal model was established by combining chronic unpredictable mild stress (CUMS) and isolated feeding. Mice were exposed to CUMS continued for 28 days, while nicotine (0.2 mg/kg) was also administrated for 28 days. Weight and sucrose consumption were measured during model establishing period. The anxiety and behavioral despair were analyzed using the forced swim test (FST) and open-field test (OFT). Spatial cognition was evaluated using Morris water maze (MWM) test. Following behavioral assessment, both long-term potentiation (LTP) and depotentiation (DEP) were recorded in the hippocampal dentate gyrus (DG) region. Both synaptic and Notch1 proteins were measured by Western. Nicotine increased stressed mouse's sucrose consumption. The MWM test showed that spatial learning and reversal learning in stressed animals were remarkably affected relative to controls, whereas nicotine partially rescued cognitive functions. Additionally, nicotine considerably alleviated the level of anxiety and the degree of behavioral despair in stressed mice. It effectively mitigated the depression-induced impairment of hippocampal synaptic plasticity, in which both the LTP and DEP were significantly inhibited in stressed mice. Moreover, nicotine enhanced the expression of synaptic and Notch1 proteins in stressed animals. The results suggest that nicotine ameliorates the depression-like symptoms and improves the hippocampal synaptic plasticity closely associated with activating transmembrane ion channel receptors and Notch signaling components. Graphical Abstract ᅟ.

Nicotine‐induced protein expression profiling reveals mutually altered proteins across four human cell lines

“…The majority of these are membrane proteins and many have roles in metabolism and are involved in intramembrane cleavage of integral membrane proteins, such as Notch receptors, as well as in APP processing. To this end, previous evidence supports the potential effect of nicotine on Notch signaling [61,62] and APP expression [39,40]. A smaller, yet interesting, cluster was composed of the proteins MSMO1, FDFT1, and CYP51A1.…”

Oxytocin receptor signaling contributes to olfactory avoidance behavior induced by an unpleasant odorant

“…Mice were brought into the room where the behavioral tests were conducted 60 min prior to the test start. Mice were placed in the center of the open-field apparatus (rectangle polycarbonate, 42×28 cm) illuminated at approximately 200 lux and allowed to explore for 5 min ( Harro et al, 1999 ; Shang et al, 2017 ). The animals were tracked to determine the amount of time spent in the center area (28×14 cm).…”

Inhibiting RIP1 Improves Chronic Stress-Induced Cognitive Impairments in D-Galactose-Induced Aging Mice

“…NMDA receptor subunits (NR1, NR2A, and NR2B) and AMPA receptor subunits (GluA1 and GluA2) are closely involved in brain function, and are also important targets of chronic stress ( Costa-Nunes et al, 2014 ; Pacheco et al, 2017 ; Shang et al, 2017 ; Arcego et al, 2018 ). The effects of chronic stress on NMDA and AMPA receptors vary based on the type of stress.…”

“…In contrast, Costa-Nunes et al (2014) found that social defeat and predation stress increased NR2A mRNA expression, but not the expression of NR2B and NR1 mRNA in the hippocampus of mice. In chronic unpredictable mild stress, the levels of NR2A and NR2B were significantly reduced ( Shang et al, 2017 ), the levels of GluA2 and GluA3 were significantly elevated while the level of GluA1 was not changed ( Lin et al, 2018 ). In the present study, we also evaluated the expression of NMDA receptor subunits (NR1, NR2A, and NR2B) and AMPA receptor subunits (GluA1 and GluA2).…”