Nicotine Inhalant via E-Cigarette Facilitates Sensorimotor Function
Recovery by Upregulating Neuronal BDNF-TrkB Signaling in Traumatic Brain
Background and Purpose: Traumatic brain injury (TBI) imposes life-long
physical, psychological, and financial burdens on affected individuals.
The current study investigated the effects of chronic nicotine exposure
via E-cigarette (E-cig) on TBI-associated behavioral and biochemical
changes. Experimental Approach: Adult C57/BL6J male mice were subjected
to controlled cortical impact (CCI) followed by daily exposure to
E-cigarette (E-Cig) vapor for six weeks. The effects of chronic nicotine
exposure on sensorimotor functions, locomotion, and sociability were
evaluated by nesting, open field, and social approach, respectively.
Immunoblots were performed to assess changes of mature brain-derived
neurotrophic factor (mBDNF) and associated downstream signaling proteins
(p-Akt and p-Erk). Histological analyses of the cortex were performed to
evaluate the effects of chronic nicotine exposure on Microglia-mediated
neuroinflammation. Key Results: Post-injury chronic nicotine exposure
significantly improved nesting performance in CCI mice. Histology
analysis revealed that chronic nicotine exposure increased the survival
of cortical neurons in the perilesion cortex. Immunoblots of cortical
tissue revealed that chronic nicotine exposure significantly upregulated
mBDNF expression, P-Erk, and p-Akt in the perilesion cortical tissue of
CCI mice. Additional IF microscopy revealed elevated mBDNF and p-Akt
expression was predominantly localized in cortical neurons of CCI mice.
Furthermore, immunolabeling of Iba1 showed that chronic nicotine
exposure attenuates microglia-mediated chronic neuroinflammation in the
perilesional cortex of CCI mice. Conclusions and Implications:
Post-injury chronic nicotine exposure via vaping facilitates
sensorimotor function recovery by upregulating neuroprotective
mBDNF/TrkB/Akt/Erk signaling. Results from this study support the
neuroprotective properties of nicotine, further investigation is needed
due to its highly addictive nature.