TY - JOUR
T1 - Dynamic endocannabinoid-mediated neuromodulation of retinal circadian circuitry
AU - Kumar, Deepak
AU - Khan, Bareera
AU - Okcay, Yagmur
AU - Sis, Çağıl Önal
AU - Abdallah, Aya
AU - Murray, Fiona
AU - Sharma, Ashish
AU - Uemura, Maiko
AU - Taliyan, Rajeev
AU - Heinbockel, Thomas
AU - Rahman, Shafiqur
AU - Goyal, Rohit
N1 - Publisher Copyright:
© 2024 Elsevier B.V.
PY - 2024/8
Y1 - 2024/8
N2 - Circadian rhythms are biological rhythms that originate from the “master circadian clock,” called the suprachiasmatic nucleus (SCN). SCN orchestrates the circadian rhythms using light as a chief zeitgeber, enabling humans to synchronize their daily physio-behavioral activities with the Earth's light-dark cycle. However, chronic/ irregular photic disturbances from the retina via the retinohypothalamic tract (RHT) can disrupt the amplitude and the expression of clock genes, such as the period circadian clock 2, causing circadian rhythm disruption (CRd) and associated neuropathologies. The present review discusses neuromodulation across the RHT originating from retinal photic inputs and modulation offered by endocannabinoids as a function of mitigation of the CRd and associated neuro-dysfunction. Literature indicates that cannabinoid agonists alleviate the SCN's ability to get entrained to light by modulating the activity of its chief neurotransmitter, i.e., γ-aminobutyric acid, thus preventing light-induced disruption of activity rhythms in laboratory animals. In the retina, endocannabinoid signaling modulates the overall gain of the retinal ganglion cells by regulating the membrane currents (Ca2+, K+, and Cl- channels) and glutamatergic neurotransmission of photoreceptors and bipolar cells. Additionally, endocannabinoids signalling also regulate the high-voltage-activated Ca2+ channels to mitigate the retinal ganglion cells and intrinsically photosensitive retinal ganglion cells-mediated glutamate release in the SCN, thus regulating the RHT-mediated light stimulation of SCN neurons to prevent excitotoxicity. As per the literature, cannabinoid receptors 1 and 2 are becoming newer targets in drug discovery paradigms, and the involvement of endocannabinoids in light-induced CRd through the RHT may possibly mitigate severe neuropathologies.
AB - Circadian rhythms are biological rhythms that originate from the “master circadian clock,” called the suprachiasmatic nucleus (SCN). SCN orchestrates the circadian rhythms using light as a chief zeitgeber, enabling humans to synchronize their daily physio-behavioral activities with the Earth's light-dark cycle. However, chronic/ irregular photic disturbances from the retina via the retinohypothalamic tract (RHT) can disrupt the amplitude and the expression of clock genes, such as the period circadian clock 2, causing circadian rhythm disruption (CRd) and associated neuropathologies. The present review discusses neuromodulation across the RHT originating from retinal photic inputs and modulation offered by endocannabinoids as a function of mitigation of the CRd and associated neuro-dysfunction. Literature indicates that cannabinoid agonists alleviate the SCN's ability to get entrained to light by modulating the activity of its chief neurotransmitter, i.e., γ-aminobutyric acid, thus preventing light-induced disruption of activity rhythms in laboratory animals. In the retina, endocannabinoid signaling modulates the overall gain of the retinal ganglion cells by regulating the membrane currents (Ca2+, K+, and Cl- channels) and glutamatergic neurotransmission of photoreceptors and bipolar cells. Additionally, endocannabinoids signalling also regulate the high-voltage-activated Ca2+ channels to mitigate the retinal ganglion cells and intrinsically photosensitive retinal ganglion cells-mediated glutamate release in the SCN, thus regulating the RHT-mediated light stimulation of SCN neurons to prevent excitotoxicity. As per the literature, cannabinoid receptors 1 and 2 are becoming newer targets in drug discovery paradigms, and the involvement of endocannabinoids in light-induced CRd through the RHT may possibly mitigate severe neuropathologies.
KW - Circadian
KW - Endocannabinoid
KW - Retina
KW - Retinohypothalamic
KW - Suprachiasmatic
UR - http://www.scopus.com/inward/record.url?scp=85198340618&partnerID=8YFLogxK
U2 - 10.1016/j.arr.2024.102401
DO - 10.1016/j.arr.2024.102401
M3 - Review article
C2 - 38964508
AN - SCOPUS:85198340618
SN - 1568-1637
VL - 99
JO - Ageing Research Reviews
JF - Ageing Research Reviews
M1 - 102401
ER -