Caspase-3 Mediated Cell Death in the Normal Development of the Mammalian Cerebellum

Abstract

Caspase-3, onto which there is a convergence of the intrinsic and extrinsic apoptotic pathways, is the main executioner of apoptosis. We here review the current literature on the intervention of the protease in the execution of naturally occurring neuronal death (NOND) during cerebellar development. We will consider data on the most common altricial species (rat, mouse and rabbit), as well as humans. Among the different types of neurons and glia in cerebellum, there is ample evidence for an intervention of caspase-3 in the regulation of NOND of the post-mitotic cerebellar granule cells (CGCs) and Purkinje neurons, as a consequence of failure to establish proper synaptic contacts with target (secondary cell death). It seems possible that the GABAergic interneurons also undergo a similar type of secondary cell death, but the intervention of caspase-3 in this case still remains to be clarified in full. Remarkably, CGCs also undergo primary cell death at the precursor/pre-migratory stage of differentiation, in this instance without the intervention of caspase-3. Glial cells, as well, undergo a process of regulated cell death, but it seems possible that expression of caspase-3, at least in the Bergmann glia, is related to differentiation rather than death.

Deregulated miR-29b-3p Correlates with Tissue-Specific Activation of Intrinsic Apoptosis in An Animal Model of Amyotrophic Lateral Sclerosis

“…As BMF has a known influence on the intrinsic apoptotic signaling cascade, it is possible that these elevated BMF expression levels may represent a mechanism that has a protective role. It is known that apoptosis in the CNS plays an enormously important physiological role during development [101]. During embryonic and early postnatal development, physiological apoptosis plays a crucial and exceptional role in the cerebellum of all mammals in order to establish the characteristic three-layered structure with their meticulous connectivity [102,103].…”

“…Especially, Purkinje cells and granule cells originated from the external granule cell layer with defective migration or aberrant projection seem to be targets of the programmed cell death [104,105]. In case of insufficient apoptosis ectopic, misplaced neurons arise that are detrimental to the whole network by failing the refinement of the neural circuits [101,106,107,108,109,110]. This seems to be confirmed by the fact that various mouse mutants, whose Purkinje cells migrate incorrectly, also display an increased programmed cell death [111,112].…”

Acute Fasting Does Not Induce Cognitive Impairment in Mice

“…Moreover, we evaluated the level of caspase-3 and cleaved caspase-3, the biomarkers of cellular apoptosis (Crowley and Waterhouse, 2016; Lossi et al, 2018), in the mice in the acute fasting group or the mice in the control group. We found that cleaved caspase-3 immunoreactivity was detected in neither the mice in the control group nor the mice in the fasting group (Figure 7B).…”

“…Thus, the imaging of c-Fos is considered to be a marker of stimulation-related neural activation and is often used as a method of visualizing neuronal networks that are activated (Kemp et al, 2013). In the present studies, we assessed the effects of acute fasting on the brain levels of c-Fos, the marker of neuronal activation, and caspase-3 activation, the marker of cellular apoptosis (Crowley and Waterhouse, 2016; Lossi et al, 2018).…”

Role of Transmembrane 4 L Six Family 1 in the Development and Progression of Cancer

“…High PCNA expression in liver cancer patients was related to increased proliferation and decreased post-operative disease-free survival time (Lim et al, 2020). Caspase-3 and caspase-9 are critical apoptotic proteases (Lossi et al, 2018). Overexpression of TM4SF1 significantly activated the phosphoinositide 3kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, which acts through the downstream apoptosis-related proteins B-cell lymphoma 2 (Bcl2), BCL-2 associated X (Bax), caspase-3, and caspase-9 to induce anti-apoptotic effects in breast cancer (Sun et al, 2015;Wei et al, 2018).…”