Exposureto noise is major contribution factor to acquired hearing loss. Hearing losscaused by acoustic overexposure is associated with cochlea injury including theloss of sensory hair cells and primary auditory neurons in cochlea. Hearingloss is the greatest cause sensory disability (WHO) affecting up to 1 in 6 of the population. It is estimatedthat approximate 20% of the burden is generated from excessive noise exposurein occupational and leisure setting (Thorneet al 2008). Sustain exposure to sound pressure level >85dBa noise leadto irreversible damage to the sensory structure of cochlea.
Once damage, themammalian sensory hair cells do not regenerate and the loss of hearing ispermanent. NIHL (Noise induce hearing loss) also excerts effects beyond theclassical pathway. NIHL suppress neurogenesis in hippocampus and alter thespatial tuning of hippocampus, neurons as animals navigate through a maze (Goble et al. 2009; Kraus 2010; Newmann2015).
Hearing loss has beenassociated with cognitive decline in the elderly and is considered to be anindependent risk factor for dementia. One of the most common causes foracquired sensorineural hearing loss is exposure to excessive noise, which hasbeen found to impair learning ability and cognitive performance in humansubjects and animal models. The mechanisms underlying the decline of cognitivefunctions after noise exposure are not entirely clear (Lijie Liu et al2016). Uran et al 2012 reported that a milddisruption in the hippocampal region after noise exposure along withsignificant behavioral abnormalities and also hypothesized that an exposure ofdeveloping rats to noise of moderate intensity was sufficient trigger change inthe hippocampus that could underlie the observed behavioral effect.
Another studywas done on male SD rats to observe the effect of chronic noise reported thatexpression of N-methyl-D-aspartic acid receptor 2B (NR2B) decreasedsignificantly which resulted in tau hyper phosphorylation and neural apoptosisin hippocampus. It may play a role in chronic noise induced neural apoptosisand cognition impairment. (Cui Bo et al. 2013). Noise could persistentlysuppress cell proliferation thereby reducing neurogenesis and also showed areduced number of DCX labeled precursor and the rate of cells in noise exposedrats.
A similar connection between total number of neuronal precursors and rateof cell proliferation has been observed in earlier studies (Kraus 2010),Currently, prosthetic devices such as hearingaids and cochlear implants are the only treatments for NIHL. Both options arecostly, and neither can mitigate cochlear injury. Therefore, there is a strongdemand for novel pharmacological or molecular treatments of hearing loss. Targetingadenosine receptorsin the cochlea has recently shown promise for the treatment of hearing loss S.M.Vlajkovic 2014). Adenosine is an endogenous neuromodulator and a cyto-protectivesubstance released from tissues in response to stress (S.
H. Snyder 1985).Adenosine can enhance endogenous antioxidant defenses, increase oxygen supply,improve blood flow, inhibit glutamate release, trigger anti-inflammatoryresponses, and promote antiapoptotic pathways (B.B. Fredholm 2007).Adenosine can also promote angiogenesis, which may be crucial in tissue repair afterinjury (T. H.
Adair 2005).In this study, we focused on the role of adenosinereceptor in development of neural injury in cochlea and different region ofhippocampus i.e. CA1, CA3, DGassociated with acoustic overexposure. Adenosine is an endogenousneuromodulator whose effects are mediated by four types G-protein coupledadenosine (A1, A2A, A2B, A3) aredifferentially localized in cochlea tissues with the strongest immuneexpression in sensory hair cell, supporting deiters cells, spiral ganglioncells (SGN), (Vljkovic et al 2007)and in hippocampus i.e.
CA1, CA3, DGregion. Thus, drugs that increase the concentration of endogenousadenosine or directly activate adenosine receptors could play a pivotal role inthe protection of the organ of Corti against cisplatin cytotoxicity.In this paperinvestigates the role of adenosine A2Areceptor signaling in theregulation of noise induce hearing loss, memory impaired and explores thetherapeutic potential of selective adenosine A2A receptor agonist CGS21680in mitigating noise induce hearing and memory impairment.