Lack of Calbindin-D28k Alters Response of the Murine Circadian Clock to Light

Abstract

A strong stimulus adjusting the circadian clock to the prevailing light-dark cycle is light. However, the circadian clock is reset by light only at specific times of the day. The mechanisms mediating such gating of light input to the CNS are not well understood. There is evidence that Ca 2+ ions play an important role in intracellular signaling mechanisms, including signaling cascades stimulated by light. Therefore, Ca 2+ is hypothesized to play a role in the light-mediated resetting of the circadian clock. Calbindin-D28k (CB; gene symbol: Calb1) is a Ca 2+ binding protein implicated in Ca 2+ homeostasis and sensing. The absence of this protein influences Ca 2+ buffering capacity of a cell, alters spatio-temporal aspects of intracellular Ca 2+ signaling, and hence might alter transmission of light information to the circadian clock in neurons of the suprachiasmatic nuclei (SCN). We tested mice lacking a functional Calb1 gene (Calb1 −/−) and found an increased phase-delay response to light applied at circadian time (CT) 14 in these animals. This is accompanied by elevated induction of Per2 gene expression in the SCN. Period length and circadian rhythmicity were comparable between Calb1 −/− and wild-type animals. Our findings indicate an involvement of CB in the signaling pathway that modulates the behavioral and molecular response to light.

Absence of the calcium-binding protein calretinin, not of calbindin D-28k, causes a permanent impairment of murine adult hippocampal neurogenesis

“…Recent evidence hints toward an additional/alternative role for CB and CR as Ca 2+ sensors, capable of influencing signaling cascades in response to intracellular Ca 2+ transients (Schwaller, 2009). Recent studies in mice lacking CB and CR by gene targeting confirm previous reports, indicating that both proteins are critical for many physiological properties (excitability, efficacy of synaptic release, resistance to hypoxia/ischemia) of the neuron expressing them and their absence may disrupt network function in some brain regions eventually affecting behavior (Schiffmann et al, 1999; Cheron et al, 2004; Schwaller et al, 2004; Farre-Castany et al, 2007; Stadler et al, 2010). …”

Sleep Deficits and Cannabis Use Behaviors: An Analysis of Shared Genetics Using Linkage Disequilibrium Score Regression and Polygenic Risk Prediction

“…Along these lines, several of the genes and genetic pathways found to be significant in sleep relatedvariable GWAS 56,58-61 have been associated with cannabis use and cannabinoid activity [62][63][64][65]67,68,[109][110][111][112] . Likewise, GWAS for lifetime cannabis use and CUD 65,66,69,70 have found genes that have been linked to sleep behaviors and circadian rhythm [71][72][73][74]113 .…”

Regional chemoarchitecture of the brain of lungfishes based on calbindin D‐28K and calretinin immunohistochemistry

“…CB and CR immunohistochemistry has been used to delineate suprachiasmatic subdivisions in many species (Fortin & Parent, ; Moore, Speh, & Leak, ; Morin, Shivers, Blanchard, & Muscat, ). In particular, the content CB, in the suprachiasmatic nucleus has been related to the control of circadian rhythms by environmental light (LeSauter, Stevens, Jansen, Lehman, & Silver, ; LeSauter, Bhuiyan, Shimazoe, & Silver, ; Arvanitogiannis, Robinson, Beaule, & Amir, ; Bryant, LeSauter, Silver, & Romero, ; Stadler, Schmutz, Schwaller, & Albrecht, ). This nucleus is the primary circadian pacemaker that reinforces the oscillations and synchronizes its components in response to light input (Welsh, Takahashi, & Kay, ).…”